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Sample records for alveolar macrophages etude

  1. The alveolar macrophage.

    OpenAIRE

    Bowden, D. H.

    1984-01-01

    The pulmonary macrophagic system is critical to the defense of the lung, keeping the alveoli clean and sterile and responding on demand with an adaptive outpouring of new cells into the air sacs. Under basal conditions alveolar macrophages, in common with other mononuclear phagocytes, are derived from the bone marrow. A population of macrophage precursors within the pulmonary interstitium provides a reserve pool capable of proliferation and delivery of phagocytes in response to unusually heav...

  2. Micronuclei in human alveolar macrophages.

    Science.gov (United States)

    D'Agostini, F; Bonatti, S; Oddera, S; De Flora, S

    1992-01-01

    Occurrence of micronuclei was monitored in pulmonary alveolar macrophages collected from 31 individuals undergoing diagnostic bronchoalveolar lavage. The overall frequency of micronucleated cells was 3.88 +/- 1.84/1000, without any significant difference attributable to sex, age, pathology, occupation, or smoking habits. The lack of influence of cigarette smoke on this clastogenicity index presumably reflects the very low rate of mitoses of macrophages in the alveolar lumen. PMID:1579732

  3. PPARs in Alveolar Macrophage Biology

    Directory of Open Access Journals (Sweden)

    Monica R. Smith

    2007-01-01

    Full Text Available PPARs, most notably PPAR-γ, play a crucial role in regulating the activation of alveolar macrophages, which in turn occupy a pivotal place in the immune response to pathogens and particulates drawn in with inspired air. In this review, we describe the dual role of the alveolar macrophage as both a first-line defender through its phagocytotic activity and a regulator of the immune response. Depending on its state of activation, the alveolar macrophage may either enhance or suppress different aspects of immune function in the lung. We then review the role of PPAR-γ and its ligands in deactivating alveolar macrophages—thus limiting the inflammatory response that, if unchecked, could threaten the essential respiratory function of the alveolus—while upregulating the cell's phagocytotic activity. Finally, we examine the role that inadequate or inappropriate PPAR-γ responses play in specific lung diseases.

  4. Tobacco smoke and the pulmonary alveolar macrophage.

    Science.gov (United States)

    Drath, D B; Davies, P; Karnovsky, M L; Huber, G L

    1979-01-01

    Our results indicate that tobacco smoke exposure to varying duration causes morphological, biochemical and functional alterations in pulmonary alveolar macrophages. The results of these changes is a population of alveolar macrophages made up of larger cells, with a reduced nucleus-cytoplasmic ratio, which are heavily loaded with heterolysosomes containing lipid. Though their fractional complement of mitochondria remains the same, an increase in the inner mitochondrial membrane surface area may be related to an enhanced oxidative metabolism. The cell is biochemically activated particularly following chronic exposure and is functionally impaired with respect to phagocytosis. PMID:232822

  5. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

    Science.gov (United States)

    Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

    2014-02-01

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

  6. Impairment of Alveolar Macrophage Transcription in Idiopathic Pulmonary Fibrosis

    OpenAIRE

    Ren, Ping; Rosas, Ivan O.; MacDonald, Sandra D.; Wu, Hai-Ping; Billings, Eric M; Gochuico, Bernadette R.

    2007-01-01

    Rationale: Alveolar macrophages are inflammatory cells that may contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF), which is characterized by excessive alveolar aggregation of cells and extracellular matrix proteins.

  7. Rituximab therapy in pulmonary alveolar proteinosis improves alveolar macrophage lipid homeostasis

    OpenAIRE

    Malur Anagha; Kavuru Mani S; Marshall Irene; Barna Barbara P; Huizar Isham; Karnekar Reema; Thomassen Mary

    2012-01-01

    Abstract Rationale Pulmonary Alveolar Proteinosis (PAP) patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF) attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and the PPARγ-regulated ATP binding cassette (ABC) lipid transpor...

  8. Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis1

    OpenAIRE

    Bessich, Jamie L.; Nymon, Amanda B.; Moulton, Lisa A; Dorman, Dana; Ashare, Alix

    2013-01-01

    Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infectio...

  9. Alveolar macrophage kinetics and function after interruption of canine marrow function

    International Nuclear Information System (INIS)

    To study the kinetics and function of alveolar macrophages after interruption of marrow function, we performed serial bronchoalveolar lavages in dogs. The studies were performed before and after 9.0 to 9.5 Grey total body irradiation and marrow infusion. Monocytes had disappeared from the bloodstream by Day 7 after the irradiation. Alveolar macrophages were significantly decreased at Day 21. At Days 14 and 21 myeloperoxidase-positive alveolar macrophages were also significantly decreased. Beyond Day 30 the number of circulating monocytes, myeloperoxidase-positive and total alveolar macrophages had returned. Sex chromatin stains of alveolar macrophages obtained from a male dog that received female marrow indicated that the repopulating macrophages were of marrow origin. In vitro studies of alveolar macrophage migration and phagocytosis demonstrated increased activities beyond Day 30. These studies suggest that in this model the alveolar macrophage is dependent on the bone marrow for support and that the alveolar macrophage depletion may impair lung defense mechanisms

  10. Degradation of pulmonary surfactant disaturated phosphatidylcholines by alveolar macrophages

    International Nuclear Information System (INIS)

    Experiments were performed to determine whether rat pulmonary surfactant disaturated phosphatidylcholines (DSPC) are degraded by alveolar macrophages in vitro. When [3H]choline-labeled surfactant materials are incubated with unlabeled alveolar macrophages, approximately 40% of the labeled DSPC is broken down in 6 h. There is just a slight decrease in the specific activity of DSPC, which suggests that most products of degradation are not reincorporated into DSPC, at least during the 6-h incubation period. There is a time- and temperature-dependent association of surfactant DSPC with alveolar macrophages, and some of the cell-associated materials are released from the cell fragments after sonication. Association of surfactant with the cells precedes degradation. The breakdown of surfactant DSPC by intact alveolar macrophages lags behind that produced by sonicated cell preparations with disrupted cell membranes. These data and other information suggest that the surfactant materials are internalized by the cells, before the breakdown. The products of degradation probably include free choline and fatty acids, most of which appear in the extracellular fluid. The breakdown processes do not seem to depend on the physical form of the surfactant or on the presence of surfactant apoproteins. Incubation of the cells alone also results in disappearance of intracellular DSPC, some of which may be surfactant phospholipid taken up by the cells in vivo. These results indicate that alveolar macrophages can degrade surfactant DSPC and suggest that these cells may be involved in catabolism of pulmonary surfactant materials

  11. Cytokinetic study of alveolar macrophage renewal in rats

    International Nuclear Information System (INIS)

    Pools of alveolar macrophages and monocytes were measured by combining morphometry and the extraction of cells by lavage. The turnover rate of macrophages was evaluated by measuring the clearance rate of 59Fe2O3 previously administered by aerosols. The labeling index and S phase duration of cells in alveoli and lung capillaries were determined by autoradiography after 3H-labeled thymidine and 5-125Iododeoxyuridine incorporation. The disappearance rate was determined after specific incorporation of 125Iododeoxyuridine in deoxyribonuclease (DNA) of alveolar macrophages. Steady-state parameters are presented. Under healthy conditions there are almost no macrophages in the interstitium space. Lung capillaries must be considered as a maturation compartment for macrophages before the last dividing stage in the alveoli. This is consistent with the large enrichment of monocytes in the lung and the ability of some of these monocytes to divide inside the capillaries

  12. Spontaneous monokine release by alveolar macrophages in chronic sarcoidosis

    OpenAIRE

    Strausz, J; Männel, Daniela N.; S. Pfeifer; A. Borkowski; Ferlinz, R.; Müller-Quernheim, J.

    1991-01-01

    In pulmonary sarcoidosis an activation of alveolar T lymphocytes and alveolar macrophages (AM) has been demonstrated. There is evidence that in contrast to acute disease a heightened T-cell response cannot be observed in the chronic phase of sarcoidosis. The role of AM in the inflammatory process of chronic sarcoidosis is not yet intensively evaluated. To address this question we measured the release of tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) by AM of 39 patients with...

  13. Depletion of resident alveolar macrophages does not prevent Fas-mediated lung injury in mice

    OpenAIRE

    Bem, R. A.; Farnand, A. W.; Wong, V; Koski, A; Rosenfeld, M. E.; Van Rooijen, N.; C. W. Frevert; Martin, T R; Matute-Bello, G.

    2008-01-01

    Activation of the Fas/Fas ligand (FasL) system in the lungs results in a form of injury characterized by alveolar epithelial apoptosis and neutrophilic inflammation. Studies in vitro show that Fas activation induces apoptosis in alveolar epithelial cells and cytokine production in alveolar macrophages. The main goal of this study was to determine the contribution of alveolar macrophages to Fas-induced lung inflammation in mice, by depleting alveolar macrophages using clodronate-containing lip...

  14. Studying the Role of Alveolar Macrophages in Breast Cancer Metastasis.

    Science.gov (United States)

    Vadrevu, Surya Kumari; Sharma, Sharad; Chintala, Navin; Patel, Jalpa; Karbowniczek, Magdalena; Markiewski, Maciej

    2016-01-01

    This paper describes the application of the syngeneic model of breast cancer (4T1) to the studies on a role of pulmonary alveolar macrophages in cancer metastasis. The 4T1 cells expressing GFP in combination with imaging and confocal microscopy are used to monitor tumor growth, track metastasizing tumor cells, and quantify the metastatic burden. These approaches are supplemented by digital histopathology that allows the automated and unbiased quantification of metastases. In this method the routinely prepared histological lung sections, which are stained with hematoxylin and eosin, are scanned and converted to the digital slides that are then analyzed by the self-trained pattern recognition software. In addition, we describe the flow cytometry approaches with the use of multiple cell surface markers to identify alveolar macrophages in the lungs. To determine impact of alveolar macrophages on metastases and antitumor immunity these cells are depleted with the clodronate-containing liposomes administrated intranasally to tumor-bearing mice. This approach leads to the specific and efficient depletion of this cell population as confirmed by flow cytometry. Tumor volumes and lung metastases are evaluated in mice depleted of alveolar macrophages, to determine the role of these cells in the metastatic progression of breast cancer. PMID:27403530

  15. Apoptosis inhibitor of macrophage (AIM) expression in alveolar macrophages in COPD

    OpenAIRE

    Kojima, Jun; Araya, Jun; Hara, Hiromichi; Ito, Saburo; Takasaka, Naoki; Kobayashi, Kenji; Fujii, Satoko; Tsurushige, Chikako; Numata, Takanori; Ishikawa, Takeo; Shimizu, Kenichiro; Kawaishi, Makoto; Saito, Keisuke; Kamiya, Noriki; Hirano, Jun

    2013-01-01

    Background Marked accumulation of alveolar macrophages (AM) conferred by apoptosis resistance has been implicated in pathogenesis of chronic obstructive pulmonary disease (COPD). Apoptosis inhibitor of macrophage (AIM), has been shown to be produced by mature tissue macrophages and AIM demonstrates anti-apoptotic property against multiple apoptosis-inducing stimuli. Accordingly, we attempt to determine if AIM is expressed in AM and whether AIM is involved in the regulation of apoptosis in the...

  16. Rituximab therapy in pulmonary alveolar proteinosis improves alveolar macrophage lipid homeostasis

    Directory of Open Access Journals (Sweden)

    Malur Anagha

    2012-06-01

    Full Text Available Abstract Rationale Pulmonary Alveolar Proteinosis (PAP patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ and the PPARγ-regulated ATP binding cassette (ABC lipid transporter, ABCG1. An open label proof of concept Phase II clinical trial was conducted in PAP patients using rituximab, a chimeric murine-human monoclonal antibody directed against B lymphocyte specific antigen CD20. Rituximab treatment decreased anti-GM-CSF antibody levels in bronchoalveolar lavage (BAL fluid, and 7/9 patients completing the trial demonstrated clinical improvement as measured by arterial blood oxygenation. Objectives This study sought to determine whether rituximab therapy would restore lipid metabolism in PAP alveolar macrophages. Methods BAL samples were collected from patients pre- and 6-months post-rituximab infusion for evaluation of mRNA and lipid changes. Results Mean PPARγ and ABCG1 mRNA expression increased 2.8 and 5.3-fold respectively (p ≤ 0.05 after treatment. Lysosomal phospholipase A2 (LPLA2 (a key enzyme in surfactant degradation mRNA expression was severely deficient in PAP patients pre-treatment but increased 2.8-fold post-treatment. In supplemental animal studies, LPLA2 deficiency was verified in GM-CSF KO mice but was not present in macrophage-specific PPARγ KO mice compared to wild-type controls. Oil Red O intensity of PAP alveolar macrophages decreased after treatment, indicating reduced intracellular lipid while extracellular free cholesterol increased in BAL fluid. Furthermore, total protein and Surfactant protein A were significantly decreased in the BAL fluid post therapy. Conclusions Reduction in GM

  17. Peptide secreted by human alveolar macrophages releases neutrophil granule contents

    International Nuclear Information System (INIS)

    A monoclonal antibody was developed against an 8000-kDa enzyme-releasing peptide (ERP) released from human alveolar macrophages. ERP was isolated on an immunoaffinity column containing the antibody bound to staphylococcal protein A-Sepharose, and by autoradiography. Release of ERP from the macrophages is not changed by plastic adherence, phagocytosis, calcium ionophore, or phorbol esters. The peptide was not antigenically similar to interferon-γ, tumor necrosis factor, or interleukin lα or 1β. The release of constituents from azurophilic and specific granules was the main identified biologic function of ERP. ERP was a more effective secretagogue in the untreated neutrophils and f-met-leu-phe was more effective in the cytochalasin B-treated neutrophils. Absorption of ERP from macrophage-conditioned medium removed a small amount of the chemotactic activity; however, the immunopurified peptide was not chemotactic or chemokinetic for neutrophils, and at high concentrations, it suppressed base line chemokinesis. Treatment of washed macrophages with trypsin released active ERP of approximately the same m.w. of spontaneously secreted ERP. These studies showed that human alveolar macrophages release a peptide which is a secretagogue for human neutrophils under conditions which may be encountered in the lungs during certain disease states. Proteolytic enzymes which are free in the lungs may release the peptide and lead to the secretion of neutrophil enzymes

  18. Virulent Coxiella burnetii Pathotypes Productively Infect Primary Human Alveolar Macrophages

    OpenAIRE

    Graham, Joseph G.; MacDonald, Laura J.; Hussain, S. Kauser; Sharma, Uma M.; Kurten, Richard C.; Voth, Daniel E.

    2013-01-01

    The intracellular bacterial pathogen Coxiella burnetii is a category B select agent that causes human Q fever. In vivo, C. burnetii targets alveolar macrophages wherein the pathogen replicates in a lysosome-like parasitophorous vacuole (PV). In vitro, C. burnetii infects a variety of cultured cell lines that have collectively been used to model the pathogen’s infectious cycle. However, differences in the cellular response to infection have been observed, and virulent C. burnetii isolate infec...

  19. Cell mechanics of alveolar epithelial cells (AECs) and macrophages (AMs).

    OpenAIRE

    Féréol, Sophie; Fodil, Redouane; Pelle, Gabriel; Louis, Bruno; Isabey, Daniel

    2008-01-01

    Cell mechanics provides an integrated view of many biological phenomena which are intimately related to cell structure and function. Because breathing constitutes a sustained motion synonymous with life, pulmonary cells are normally designed to support permanent cyclic stretch without breaking, while receiving mechanical cues from their environment. The authors study the mechanical responses of alveolar cells, namely epithelial cells and macrophages, exposed to well-controlled mechanical stre...

  20. Alveolar macrophages in rabbits exposed to nickel dust

    Energy Technology Data Exchange (ETDEWEB)

    Camner, P.; Johansson, A.; Lundborg, M.

    1978-07-01

    Two groups of four rabbits each were exposed to 0.5 and 2.0 mg/m/sup 3/ of metallic nickel dust respectively, for 4 weeks (5 days/week, 6 hours/day). About half of the particle masses penetrated a Casella preseparator. After exposure the lungs were extracted and lavaged. Compared to four control rabbits significant effects were seen in both exposed groups with regard to lung weight and density as well as phagocytic activity, size distribution, and ultrastructure of the alveolar macrophages (numerous slender microvilli and long protrusions from the cell surface and laminated structures similar to those seen in alveolar type II cells). The effects on the macrophages were probably not caused directly by nickel. The lung washing from the exposed rabbits contained an amorphous substance rich in phospholipids and laminated structures. Apart from the ultrastructural changes the effects seemed to be dose related. The results of exposure to metallic nickel dust have at least some features in common with ''alveolar lipoproteinosis,'' described in rats exposed to silica dust, and with ''pulmonary alveolar proteinosis,'' described in man.

  1. Mechanisms of pulmonary fibrosis. Spontaneous release of the alveolar macrophage-derived growth factor in the interstitial lung disorders.

    OpenAIRE

    Bitterman, P B; Adelberg, S; Crystal, R G

    1983-01-01

    Interstitial lung disorders are characterized both by a chronic inflammation of the lower respiratory tract that includes increased numbers of activated alveolar macrophages and by increased numbers of fibroblasts within the alveolar wall. Since alveolar macrophages from normal individuals can be activated to release a growth factor for lung fibroblasts (alveolar macrophage-derived growth factor [AMDGF]), we hypothesized that the activated alveolar macrophages within the lower respiratory tra...

  2. Alveolar macrophages regulate neutrophil recruitment in endotoxin-induced lung injury

    Directory of Open Access Journals (Sweden)

    Reyes Livia

    2005-06-01

    Full Text Available Abstract Background Alveolar macrophages play an important role during the development of acute inflammatory lung injury. In the present study, in vivo alveolar macrophage depletion was performed by intratracheal application of dichloromethylene diphosphonate-liposomes in order to study the role of these effector cells in the early endotoxin-induced lung injury. Methods Lipopolysaccharide was applied intratracheally and the inflammatory reaction was assessed 4 hours later. Neutrophil accumulation and expression of inflammatory mediators were determined. To further analyze in vivo observations, in vitro experiments with alveolar epithelial cells and alveolar macrophages were performed. Results A 320% increase of polymorphonuclear leukocytes in bronchoalveolar lavage fluid was observed in macrophage-depleted compared to macrophage-competent lipopolysaccharide-animals. This neutrophil recruitment was also confirmed in the interstitial space. Monocyte chemoattractant protein-1 concentration in bronchoalveolar lavage fluid was significantly increased in the absence of alveolar macrophages. This phenomenon was underlined by in vitro experiments with alveolar epithelial cells and alveolar macrophages. Neutralizing monocyte chemoattractant protein-1 in the airways diminished neutrophil accumulation. Conclusion These data suggest that alveolar macorphages play an important role in early endotoxin-induced lung injury. They prevent neutrophil influx by controlling monocyte chemoattractant protein-1 production through alveolar epithelial cells. Alveolar macrophages might therefore possess robust anti-inflammatory effects.

  3. DMPD: Silica binding and toxicity in alveolar macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available r SA, Holian A. Free Radic Biol Med. 2008 Apr 1;44(7):1246-58. Epub 2007 Dec 27. (.png) (.svg) (.html) (.csm...city in alveolar macrophages. Authors Hamilton RF Jr, Thakur SA, Holian A. Publication Free Radic Biol Med

  4. Self-renewal of pulmonary alveolar macrophages: evidence from radiation chimera studies

    International Nuclear Information System (INIS)

    Radiation-induced chimeric mice were used to study the origin of pulmonary alveolar macrophages. Unlike in other studies, these radiation chimeras were prepared by using a special fractionated irradiation regimen to minimize the killing of alveolar macrophage colony-forming cells, putative local stem cells. For this study CBA mice with or without T6 chromosome marker were used. Under this experimental condition, the majority of alveolar macrophages in mitosis are of host origin even after 45 weeks. These data suggest that alveolar macrophages are a self-renewing population under normal steady-state conditions

  5. The role of the alveolar macrophage in jaagsiekte

    International Nuclear Information System (INIS)

    The increase of alveolar macrophages in jaagsiekte sheep lungs is not caused by excessive surfactant production but is due to a chemotactic factor secreted by the tumour cells. Both growth inhibitory and growth stimulatory factors were detected in vitro in medium from cultures of lung lavage cells exposed to jaagsiekte tumour cell supernatant. The macrophage component of the lavage cells was found to produce a growth stimulatory factor that was replaced by a growth inhibitory factor following exposure to jaagsiekte tumour cell supernatant. Whether these factors stimulated or inhibited DNA synthesis depended to some extent on whether the indicators cells were transformed or not. Alveolar macrophages infected with lentivirus were found to be chemotactically inhibited as well as having a reduced leukocine production potential. Peripheral blood monocytes isolated from sheep suffering with acute jaagsiekte were depressed with regard to their DNA synthesis potential. 3H-thymidine incorporation assay was used to determine if there was any difference in the division potential of blood monocytes isolated from JS-sheep compared to normal sheep

  6. Trace elements in human alveolar macrophages studied by PIXE

    Science.gov (United States)

    Weber, G.; Roelandts, I.; Corhay, J. L.; Radermecker, M.; Delavignette, J. P.

    1990-04-01

    The purpose of this study is to determine the metal content of alveolar macrophages by PIXE from 94 subjects divided into two groups as follows: group (1) — subjects with non-occupational exposure to industrial dust: 30 healthy volunteers (controls), 16 patients suffering from lung cancer; group (2) — 48 healthy steel workers from the Liège area (blast-furnace [ n=29] and coke oven [ n=19]). We hope to define more precisely the influence of carcinoma, smoking habit, pathology and occupational exposure in the steel industry on the macrophage metal content. This study has shown: (a) an Fe and Sr increase and a Br decrease in the macrophages of smokers (especially in heavy smokers): (b) a significant Fe, Ti, Br and Cu increase and a trend to Pb, Cr, As and Sr increase in macrophages of healthy steel workers (especially blast-furnace workers) in comparison with non-exposed controls; (c) a significant Fe, Br, Cu and Zn increase and a trend to Pb, As and Ni increase in macrophages of non-exposed patients with lung cancer by comparison with non-exposed controls. The mechanism of metal change could be explained by professional exposure and endogenous changes (protein synthesis, inflammation, bronchial bleeding, …)

  7. Role of alveolar macrophage lysosomes in metal detoxification.

    Science.gov (United States)

    Berry, J P; Zhang, L; Galle, P; Ansoborlo, E; Hengé-Napoli, M H; Donnadieu-Claraz, M

    1997-02-15

    The intracellular behaviour of different toxic mineral elements inhaled as soluble aerosols or as insoluble particles was studied in the rat by electron microscopy, electron probe microanalysis, and electron microdiffraction. This study showed that, after inhalation, aerosols of soluble elements like cerous chloride, chromic chloride, uranyl nitrate, and aluminium chloride, are concentrated in the lysosomes of alveolar macrophages and are precipitated in the lysosomes in the form of insoluble phosphate, probably due to the activity of acid phosphatase (intralysosomial enzyme). Also, after inhalation of crystalline particles that are insoluble or poorly soluble in water such as the illites (phyllosilicates), ceric oxides (opaline), and industrial uranium oxides (U3O8), the small crystals are captured by the alveolar macrophage lysosomes and transformed over time into an amorphous form. This structural transformation is associated with changes in the chemical nature of particles inhaled in the oxide form. Microanalysis of amorphous deposits observed after inhalation of uranium or ceric oxides has shown that they contain high concentrations of phosphorus associated with the initial elements cerium and uranium. These different processes tend to limit the diffusion of these toxic elements within the organism, whether they are inhaled in soluble form or not. PMID:9140931

  8. Pulmonary alveolar proteinosis, a primary immunodeficiency of impaired GM-CSF stimulation of macrophages

    OpenAIRE

    Trapnell, Bruce C.; Carey, Brenna C.; Uchida, Kanji; Suzuki, Takuji

    2009-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of pulmonary surfactant, respiratory insufficiency, and increased infections. It occurs in various clinical settings that disrupt surfactant catabolism in alveolar macrophages, including a relatively more common autoimmune disease caused by GM-CSF autoantibodies and a rare congenital disease caused by CSF2RA mutations. Recent results demonstrate that GM-CSF is critical for alveolar macrophage terminal differ...

  9. Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Chuan Junlan [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Li Yanzhen [Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery Technology and Pharmacokinetics (China); Yang Likai; Sun Xun [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Zhang Qiang [Peking University, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences (China); Gong Tao, E-mail: gongtaoy@126.com; Zhang Zhirong, E-mail: zrzzl@vip.sina.com [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China)

    2013-05-15

    The present study aimed at developing a drug delivery system targeting the densest site of tuberculosis infection, the alveolar macrophages (AMs). Rifampicin (RFP)-loaded solid lipid nanoparticles (RFP-SLNs) with an average size of 829.6 {+-} 16.1 nm were prepared by a modified lipid film hydration method. The cytotoxicity of RFP-SLNs to AMs and alveolar epithelial type II cells (AECs) was examined using MTT assays. The viability of AMs and AECs was above 80 % after treatment with RFP-SLNs, which showed low toxicity to both AMs and AECs. Confocal Laser Scanning Microscopy was employed to observe the interaction between RFP-SLNs and both AMs and AECs. After incubating the cells with RFP-SLNs for 2 h, the fluorescent intensity in AMs was more and remained longer (from 0.5 to 12 h) when compared with that in AECs (from 0.5 to 8 h). In vitro uptake characteristics of RFP-SLNs in AMs and AECs were also investigated by detection of intracellular RFP by High performance liquid chromatography. Results showed that RFP-SLNs delivered markedly higher RFP into AMs (691.7 ng/mg in cultured AMs, 662.6 ng/mg in primary AMs) than that into AECs (319.2 ng/mg in cultured AECs, 287.2 ng/mg in primary AECs). Subsequently, in vivo delivery efficiency and the selectivity of RFP-SLNs were further verified in Sprague-Dawley rats. Under pulmonary administration of RFP-SLNs, the amount of RFP in AMs was significantly higher than that in AECs at each time point. Our results demonstrated that solid lipid nanoparticles are a promising strategy for the delivery of rifampicin to alveolar macrophages selectively.

  10. Expression of functions by normal sheep alveolar macrophages and their alteration by interaction with Mycoplasma ovipneumoniae.

    Science.gov (United States)

    Niang, M; Rosenbusch, R F; Lopez-Virella, J; Kaeberle, M L

    1997-10-31

    Normal sheep alveolar macrophages collected by bronchial lavage were exposed to live or heat-killed Mycoplasma ovipneumoniae organisms, and their capability to ingest Staphylococcus aureus and to elicit antibody-dependent cellular cytotoxicity against sensitized chicken red blood cells was tested. Controls consisted of non-infected macrophages in M199 medium. In addition, the effect of M. ovipneumoniae on expression of surface molecules on these sheep alveolar macrophages was determined. The percentage of S. aureus ingested by nontreated sheep alveolar macrophages was significantly higher than that of infected macrophages. Live mycoplasmas were more effective in suppressing the ingestion of S. aureus by these macrophages than killed mycoplasmas. Both live and killed mycoplasmas suppressed the cytolytic effect of the sheep alveolar macrophages to a similar degree. About 78% and 45% of the normal sheep alveolar macrophages had IgG and complement receptors, respectively. Infection of these macrophages with M. ovipneumoniae decreased significantly the expression of IgG receptors but had no effects on complement receptors. There were substantial increases in the expression of both MHC class I and class II by the mycoplasma-induced macrophages as compared with unstimulated macrophages. Live mycoplasmas were more effective in inducing expression of both classes than killed mycoplasmas. The results, taken together, suggest that M. ovipneumoniae induced alterations in macrophage activities and this may be a contributing factor in the pathogenesis of respiratory disease induced by the organism.

  11. Inhibition of immunological function mediated DNA damage of alveolar macrophages caused by cigarette smoke in mice.

    Science.gov (United States)

    Ishida, Takahiro; Hirono, Yuriko; Yoshikawa, Kenichi; Hutei, Yoshimi; Miyagawa, Mayuko; Sakaguchi, Ikuyo; Pinkerton, Kent E; Takeuchi, Minoru

    2009-12-01

    Exposure to cigarette smoke impairs the pulmonary immune system, including alveolar macrophage function, although the mechanisms by which this occurs are not fully elucidated. This study investigates the effect of cigarette smoke exposure on the antigen-presenting activity of alveolar macrophages, which is required for antigen-specific response to T cells. C57BL/6 mice were exposed to cigarette smoke for 10 days using a Hamburg II smoking machine, and alveolar macrophages were obtained by bronchoalveolar lavage. The antigen-presenting activity of alveolar macrophages was significantly inhibited in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. Major histocompatibility complex class II cell surface molecule-positive cells, B7-1 molecule-positive cells, and interleukin-1beta messenger RNA gene expression in alveolar macrophages were significantly decreased in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. In contrast, DNA damage and generation of superoxide and hydrogen peroxide in alveolar macrophages were significantly increased by cigarette smoke exposure. These results suggest that inhibition of the antigen-presenting activity of alveolar macrophages may result from decreased expression of major histocompatibility complex class II and B7-1 molecules and interleukin-1beta messenger RNA gene expression following cigarette smoke exposure. Furthermore, inhibition of antigen presentation in alveolar macrophage may result from DNA damage induced by excessive amounts of reactive oxygen species being generated by alveolar macrophages following cigarette smoke exposure. These findings suggest that cigarette smoke impairs the immunological function of alveolar macrophages and, as a result, increases the risk for pulmonary infection. PMID:19922407

  12. Alveolar macrophages regulate neutrophil recruitment in endotoxin-induced lung injury

    OpenAIRE

    Beck-Schimmer, B; Schwendener, R.; Pasch, T; Reyes, L.; Booy, C; Schimmer, R C

    2005-01-01

    BACKGROUND: Alveolar macrophages play an important role during the development of acute inflammatory lung injury. In the present study, in vivo alveolar macrophage depletion was performed by intratracheal application of dichloromethylene diphosphonate-liposomes in order to study the role of these effector cells in the early endotoxin-induced lung injury. METHODS: Lipopolysaccharide was applied intratracheally and the inflammatory reaction was assessed 4 hours later. Neutrophil accumulation an...

  13. Alveolar macrophages regulate neutrophil recruitment in endotoxin-induced lung injury

    OpenAIRE

    Reyes Livia; Pasch Thomas; Schwendener Reto; Beck-Schimmer Beatrice; Booy Christa; Schimmer Ralph C

    2005-01-01

    Abstract Background Alveolar macrophages play an important role during the development of acute inflammatory lung injury. In the present study, in vivo alveolar macrophage depletion was performed by intratracheal application of dichloromethylene diphosphonate-liposomes in order to study the role of these effector cells in the early endotoxin-induced lung injury. Methods Lipopolysaccharide was applied intratracheally and the inflammatory reaction was assessed 4 hours later. Neutrophil accumula...

  14. Functional and metabolic properties of alveolar macrophages in response to the gas phase of tobacco smoke.

    OpenAIRE

    Drath, D B; Shorey, J M; Huber, G L

    1981-01-01

    The effect of whole tobacco smoke and the gas phase of tobacco smoke on the metabolism and phagocytic ability of alveolar macrophages was monitored over a 30-day exposure period. It was demonstrated that both the gas phase and whole tobacco smoke induced a weight loss in exposed rats. Alveolar macrophage oxygen consumption was markedly increased by both exposure regimens. Superoxide generation was not affected by whole tobacco smoke exposure but was increased in response to the filtered gas p...

  15. Activated alveolar macrophages in subclinical pulmonary inflammation in collagen vascular diseases.

    OpenAIRE

    Wallaert, B; Bart, F.; Aerts, C.; Ouaissi, A.; Hatron, P Y; Tonnel, A. B.; C. Voisin

    1988-01-01

    A study was initiated to determine whether alveolar macrophages from patients with collagen vascular diseases but free of pulmonary symptoms were spontaneously activated and whether they released various mediators related to the pathogenesis of pulmonary fibrosis. Alveolar macrophages obtained by bronchoalveolar lavage from 32 patients with proved collagen vascular disease but no evidence of lung disease were compared with those from 10 patients with collagen vascular disease with interstitia...

  16. Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy

    Science.gov (United States)

    Grimm, Melissa J.; D'Auria, Anthony C.; Segal, Brahm H.

    2014-01-01

    The lung is an interface where host cells are routinely exposed to microbes and microbial products. Alveolar macrophages are the first-line phagocytic cells that encounter inhaled fungi and other microbes. Macrophages and other immune cells recognize Aspergillus motifs by pathogen recognition receptors and initiate downstream inflammatory responses. The phagocyte NADPH oxidase generates reactive oxygen intermediates (ROIs) and is critical for host defense. Although NADPH oxidase is critical for neutrophil-mediated host defense1-3, the importance of NADPH oxidase in macrophages is not well defined. The goal of this study was to delineate the specific role of NADPH oxidase in macrophages in mediating host defense against A. fumigatus. We found that NADPH oxidase in alveolar macrophages controls the growth of phagocytosed A. fumigatus spores4. Here, we describe a method for assessing the ability of mouse alveolar macrophages (AMs) to control the growth of phagocytosed Aspergillus spores (conidia). Alveolar macrophages are stained in vivo and ten days later isolated from mice by bronchoalveolar lavage (BAL). Macrophages are plated onto glass coverslips, then seeded with green fluorescent protein (GFP)-expressing A. fumigatus spores. At specified times, cells are fixed and the number of intact macrophages with phagocytosed spores is assessed by confocal microscopy. PMID:25045941

  17. The localization of catalase in the pulmonary alveolar macrophage.

    Science.gov (United States)

    Davies, P; Drath, D B; Engel, E E; Huber, G L

    1979-02-01

    A combined biochemical and cytochemical study of catalase was performed on alveolar macrophages lavaged from the lungs of adult male rats. Biochemically, catalase activity was present in both a high-speed granule fraction and in the supernatant. The granule-associated activity exhibited latency. Two methods of cell breakage, sonication and homogenization, yielded similar levels and distributions of catalase activity. Catalase activity in whole cells was identified cytochemically by the alkaline diaminobenzidine method and was localized within membrane-lined cytoplasmic granules similar in size to microperoxisomes and associated with cisternae of smooth endoplasmic reticulum. Localization of the reaction product was inhibited by 0.04 M aminotriazole, by cyanide, and by boiling prior to incubation. The cytochemical reaction continued in the absence of exogenous peroxide, but could be prevented by addition of catalase or pyruvate to the peroxide-free medium. Enzyme activity was also localized within a portion of the membrane-bound granules present in the cell fractions used for the biochemical assays. PMID:431040

  18. Evidence for particle transport between alveolar macrophages in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Benson, J.M.; Nikula, K.J.; Guilmette, R.A.

    1995-12-01

    Recent studies at this Institute have focused on determining the role of alveolar macrophages (AMs) in the transport of particles within and form the lung. For those studies, AMs previously labeled using the nuclear stain Hoechst 33342 and polychromatic Fluoresbrite microspheres (1 {mu}m diameter, Polysciences, Inc., Warrington, PA) were instilled into lungs of recipient F344 rats. The fate of the donor particles and the doubly labeled AMs within recipient lungs was followed for 32 d. Within 2-4 d after instillation, the polychromatic microspheres were found in both donor and resident AMs, suggesting that particle transfer occurred between the donor and resident AMs. However, this may also have been an artifact resulting from phagocytosis of the microspheres form dead donor cells or from the fading or degradation of Hoechst 33342 within the donor cells leading to their misidentification as resident AMs. The results support the earlier findings that microspheres in donor AMs can be transferred to resident AMs within 2 d after instillation.

  19. Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype.

    Directory of Open Access Journals (Sweden)

    Shikha Bhatia

    Full Text Available The ubiquitous fungus Aspergillus fumigatus is associated with chronic diseases such as invasive pulmonary aspergillosis in immunosuppressed patients and allergic bronchopulmonary aspergillosis (ABPA in patients with cystic fibrosis or severe asthma. Because of constant exposure to this fungus, it is critical for the host to exercise an immediate and decisive immune response to clear fungal spores to ward off disease. In this study, we observed that rapidly after infection by A. fumigatus, alveolar macrophages predominantly express Arginase 1 (Arg1, a key marker of alternatively activated macrophages (AAMs. The macrophages were also found to express Ym1 and CD206 that are also expressed by AAMs but not NOS2, which is expressed by classically activated macrophages. The expression of Arg1 was reduced in the absence of the known signaling axis, IL-4Rα/STAT6, for AAM development. While both Dectin-1 and TLR expressed on the cell surface have been shown to sense A. fumigatus, fungus-induced Arg1 expression in CD11c(+ alveolar macrophages was not dependent on either Dectin-1 or the adaptor MyD88 that mediates intracellular signaling by most TLRs. Alveolar macrophages from WT mice efficiently phagocytosed fungal conidia, but those from mice deficient in Dectin-1 showed impaired fungal uptake. Depletion of macrophages with clodronate-filled liposomes increased fungal burden in infected mice. Collectively, our studies suggest that alveolar macrophages, which predominantly acquire an AAM phenotype following A. fumigatus infection, have a protective role in defense against this fungus.

  20. MODULATION OF EICOSANOID PRODUCTION BY HUMAN ALVEOLAR MACROPHAGES EXPOSED TO SILICA IN VITRO

    Science.gov (United States)

    Repeated inhalation of silica dust can lead to inflammation and fibrosis in human lung and in experimental animal models. he alveolar macrophage is believed to play a pivotal role in this process. umerous macrophage-derived growth factors, cytokines and arachidonic acid metabolit...

  1. Assessment of mineral dust cytotoxicity toward rat alveolar macrophages using a 51Cr release assay

    International Nuclear Information System (INIS)

    An assay was developed to assess the cytotoxicity of mineral dust by measuring release of 51Cr from prelabeled rat alveolar macrophages. Optimal conditions for the assay are described, the most notable being use of 2% albumin instead of fetal calf serum. The assay demonstrated loss of label into the supernatant when prelabeled macrophages were cultured with the two pathogenic mineral dusts, quartz and chrysotile asbestos. In contrast the inert mineral dust titanium dioxide had very little effect on 51Cr release by rat alveolar macrophages

  2. Effect of porcine reproductive and respiratory syndrome virus (PRRSV) on alveolar lung macrophage survival and function

    DEFF Research Database (Denmark)

    Oleksiewicz, Martin B.; Nielsen, Jens

    1999-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) recently emerged as an important cause of reproductive disorders and pneumonia in domestic pigs throughout the world. Acute cytocidal replication of PRRSV in alveolar lung macrophages causes the acute pneumonia; however, it remains largely...... unresolved whether there may also be a predisposition to longer-term local immunodeficiency in the PRRSV-convalescent lung. We applied various flow cytometric techniques to study the interplay between PRRSV replication and macrophage viability/function in pure cultures of porcine alveolar lung macrophages....... Monitored by flow cytometric detection of intracellular PRRSV nucleocapsid protein, acute (24 h post infection) PRRSV replication did not impede the ability of alveolar macrophages to ingest fluorescently labelled Escherichia coli. At 48 h post infection, PRRSV-induced cytotoxicity (quantitated by flow...

  3. Oxygen dependence of human alveolar macrophage-mediated antibody-dependent cytotoxicity.

    OpenAIRE

    Conkling, P.; Papermaster-Bender, G; Whitcomb, M; Sagone, A L

    1982-01-01

    We studied the metabolic characteristics of the human alveolar macrophage-mediated antibody-dependent cytotoxicity (ADCC) reaction, using an anti-D sensitized human erythrocyte target system. Metabolic experiments demonstrated a high resting rate of glucose metabolism in macrophages, but no oxidative metabolic burst was found to accompany the ADCC reaction. These findings were confirmed by oxygen consumption studies, showing a high resting rate of oxygen consumption by macrophages, but no cha...

  4. PPARγ regulates the expression of cholesterol metabolism genes in alveolar macrophages

    International Nuclear Information System (INIS)

    Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear transcription factor involved in lipid metabolism that is constitutively expressed in the alveolar macrophages of healthy individuals. PPARγ has recently been implicated in the catabolism of surfactant by alveolar macrophages, specifically the cholesterol component of surfactant while the mechanism remains unclear. Studies from other tissue macrophages have shown that PPARγ regulates cholesterol influx, efflux, and metabolism. PPARγ promotes cholesterol efflux through the liver X receptor-alpha (LXRα) and ATP-binding cassette G1 (ABCG1). We have recently shown that macrophage-specific PPARγ knockout (PPARγ KO) mice accumulate cholesterol-laden alveolar macrophages that exhibit decreased expression of LXRα and ABCG1 and reduced cholesterol efflux. We hypothesized that in addition to the dysregulation of these cholesterol efflux genes, the expression of genes involved in cholesterol synthesis and influx was also dysregulated and that replacement of PPARγ would restore regulation of these genes. To investigate this hypothesis, we have utilized a Lentivirus expression system (Lenti-PPARγ) to restore PPARγ expression in the alveolar macrophages of PPARγ KO mice. Our results show that the alveolar macrophages of PPARγ KO mice have decreased expression of key cholesterol synthesis genes and increased expression of cholesterol receptors CD36 and scavenger receptor A-I (SRA-I). The replacement of PPARγ (1) induced transcription of LXRα and ABCG1; (2) corrected suppressed expression of cholesterol synthesis genes; and (3) enhanced the expression of scavenger receptors CD36. These results suggest that PPARγ regulates cholesterol metabolism in alveolar macrophages.

  5. Cytokinetic behavior of pulmonary alveolar macrophages in monocytopenic mice

    International Nuclear Information System (INIS)

    The cytokinetic behavior of pulmonary alveolar macrophages (PAM) was studied by pulse labeling with 3HTdB in mice made monocytopenic by a single intravenous injection of the bone-seeking isotope strontium-89 (99Sr). In the presence or absence of blood monocytes, PAM population size was unchanged for up to 1 month of chronic, severe monocytopenia. Pulse-labeling studies performed during monocytopenia show that in control mice PAM population half-times were 17.8 days with a potential doubling time of 39 days, whereas T1/2 was 14.8 days with a 28.5 day population doubling time for PAM in 99Sr-treated mice. Analysis of the halving times of the PAM mean grain count and the halving times of the most highly pulse-labeled cohorts suggested that PAM cell cycle times (Tc) were 5.1 days with a PAM rate of disappearance of 10.8%/day in 99Sr-treated mice and Tc of 6.6 days with a PAM rate of disappearance of 11.4%/day in 99Sr-treated mice. As measured by 3HTdR-labeling techniques, these cytokinetic values are in close approximation to each other, suggesting that 99Sr treatment did not significantly alter either PAM population size or cytokinetic behavior. Employing experimental values it was possible to construct a simple model of PAM population growth that supports the concept that the PAM population is self-renewing in the adult mouse. Taken together, the data show that a major portion of the resident PAM need not depend on the daily influx of peripheral blood monocytes to maintain themselves in a kinetically steady state

  6. Activation of Alveolar Macrophages via the Alternative Pathway in Herpesvirus-Induced Lung Fibrosis

    OpenAIRE

    Mora, Ana L.; Torres-González, Edilson; Rojas, Mauricio; Corredor, Claudia; Ritzenthaler, Jeffrey; Xu, Jianguo; Roman, Jesse; Brigham, Kenneth; Stecenko, Arlene

    2006-01-01

    The etiology of idiopathic pulmonary fibrosis (IPF) is unknown. Because viral pathogenesis of IPF has been suggested, we have established a murine model of progressive pulmonary fibrosis by infecting IFN-γR–deficient mice (IFN-γR−/−) with the murine γ-herpesvirus 68. Because alveolar macrophages in humans with IPF have been implicated in driving the profibrotic response, we studied their role in our model. Chronic herpesvirus infection of the lung was associated with recruitment of alveolar m...

  7. Nontypeable Haemophilus influenzae Clearance by Alveolar Macrophages Is Impaired by Exposure to Cigarette Smoke ▿ †

    Science.gov (United States)

    Martí-Lliteras, Pau; Regueiro, Verónica; Morey, Pau; Hood, Derek W.; Saus, Carles; Sauleda, Jaume; Agustí, Alvar G. N.; Bengoechea, José Antonio; Garmendia, Junkal

    2009-01-01

    Nontypeable Haemophilus influenzae (NTHI) is an opportunistic gram-negative pathogen that causes respiratory infections and is associated with progression of respiratory diseases. Cigarette smoke is a main risk factor for development of respiratory infections and chronic respiratory diseases. Glucocorticoids, which are anti-inflammatory drugs, are still the most common therapy for these diseases. Alveolar macrophages are professional phagocytes that reside in the lung and are responsible for clearing infections by the action of their phagolysosomal machinery and promotion of local inflammation. In this study, we dissected the interaction between NTHI and alveolar macrophages and the effect of cigarette smoke on this interaction. We showed that alveolar macrophages clear NTHI infections by adhesion, phagocytosis, and phagolysosomal processing of the pathogen. Bacterial uptake requires host actin polymerization, the integrity of plasma membrane lipid rafts, and activation of the phosphatidylinositol 3-kinase (PI3K) signaling cascade. Parallel to bacterial clearance, macrophages secrete tumor necrosis factor alpha (TNF-α) upon NTHI infection. In contrast, exposure to cigarette smoke extract (CSE) impaired alveolar macrophage phagocytosis, although NTHI-induced TNF-α secretion was not abrogated. Mechanistically, our data showed that CSE reduced PI3K signaling activation triggered by NTHI. Treatment of CSE-exposed cells with the glucocorticoid dexamethasone reduced the amount of TNF-α secreted upon NTHI infection but did not compensate for CSE-dependent phagocytic impairment. The deleterious effect of cigarette smoke was observed in macrophage cell lines and in human alveolar macrophages obtained from smokers and from patients with chronic obstructive pulmonary disease. PMID:19620348

  8. Functional and metabolic properties of alveolar macrophages in response to the gas phase of tobacco smoke

    Energy Technology Data Exchange (ETDEWEB)

    Drath, D.B.; Shorey, J.M.; Huber, G.L.

    1981-10-01

    The effect of whole tobacco smoke and the gas phase of tobacco smoke on the metabolism and phagocytic ability of alveolar macrophages was monitored over a 30-day exposure period. It was demonstrated that both the gas phase and whole tobacco smoke induced a weight loss in exposed rats. Alveolar macrophage oxygen consumption was markedly increased by both exposure regimens. Superoxide generation was not affected by whole tobacco smoke exposure but was increased in response to the filtered gas phase. Hexose monophosphate shunt activity was not altered by either treatment. When metabolic alterations were seen in response to the separate exposures, they were seen only after a phagocytic challenge to the macrophage and not when the cell was unchallenged. Neither whole tobacco smoke nor the gas phase had any significant effect on the ability of alveolar macrophages to phagocytize a viable challenge of Staphylococcus aureus. Our results suggest that many of the metabolic and functional effects of tobacco smoke on alveolar macrophages can be attributed to the gas-phase component of whole tobacco smoke.

  9. Functional and metabolic properties of alveolar macrophages in response to the gas phase of tobacco smoke.

    Science.gov (United States)

    Drath, D B; Shorey, J M; Huber, G L

    1981-10-01

    The effect of whole tobacco smoke and the gas phase of tobacco smoke on the metabolism and phagocytic ability of alveolar macrophages was monitored over a 30-day exposure period. It was demonstrated that both the gas phase and whole tobacco smoke induced a weight loss in exposed rats. Alveolar macrophage oxygen consumption was markedly increased by both exposure regimens. Superoxide generation was not affected by whole tobacco smoke exposure but was increased in response to the filtered gas phase. Hexose monophosphate shunt activity was not altered by either treatment. When metabolic alterations were seen in response to the separate exposures, they were seen only after a phagocytic challenge to the macrophage and not when the cell was unchallenged. Neither whole tobacco smoke nor the gas phase had any significant effect on the ability of alveolar macrophages to phagocytize a viable challenge of Staphylococcus aureus. Our results suggest that many of the metabolic and functional effects of tobacco smoke on alveolar macrophages can be attributed to the gas-phase component of whole tobacco smoke. PMID:6271676

  10. Elemental analysis of lung tissue particles and intracellular iron content of alveolar macrophages in pulmonary alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    Ohkubo Takeru

    2011-06-01

    Full Text Available Abstract Background Pulmonary alveolar proteinosis (PAP is a rare disease occurred by idiopathic (autoimmune or secondary to particle inhalation. The in-air microparticle induced X-ray emission (in-air micro-PIXE system performs elemental analysis of materials by irradiation with a proton microbeam, and allows visualization of the spatial distribution and quantitation of various elements with very low background noise. The aim of this study was to assess the secondary PAP due to inhalation of harmful particles by employing in-air micro-PIXE analysis for particles and intracellular iron in parafin-embedded lung tissue specimens obtained from a PAP patient comparing with normal lung tissue from a non-PAP patient. The iron inside alveolar macrophages was stained with Berlin blue, and its distribution was compared with that on micro-PIXE images. Results The elements composing particles and their locations in the PAP specimens could be identified by in-air micro-PIXE analysis, with magnesium (Mg, aluminum (Al, silicon (Si, phosphorus (P, sulfur (S, scandium (Sc, potassium (K, calcium (Ca, titanium (Ti, chromium (Cr, copper (Cu, manganase (Mn, iron (Fe, and zinc (Zn being detected. Si was the major component of the particles. Serial sections stained by Berlin blue revealed accumulation of sideromacrophages that had phagocytosed the particles. The intracellular iron content of alveolar macrophage from the surfactant-rich area in PAP was higher than normal lung tissue in control lung by both in-air micro-PIXE analysis and Berlin blue staining. Conclusion The present study demonstrated the efficacy of in-air micro-PIXE for analyzing the distribution and composition of lung particles. The intracellular iron content of single cells was determined by simultaneous two-dimensional and elemental analysis of paraffin-embedded lung tissue sections. The results suggest that secondary PAP is associated with exposure to inhaled particles and accumulation of iron in

  11. Small alveolar macrophages are infected preferentially by HIV and exhibit impaired phagocytic function

    OpenAIRE

    Jambo, K C; Banda, D H; Kankwatira, A M; Sukumar, N.; Allain, T J; Heyderman, R. S.; Russell, D. G.; Mwandumba, H. C.

    2014-01-01

    HIV-1-infected persons are at higher risk of lower respiratory tract infections than HIV-1-uninfected individuals. This suggests strongly that HIV-infected persons have specific impairment of pulmonary immune responses, but current understanding of how HIV alters pulmonary immunity is incomplete. Alveolar macrophages (AMs), comprising small and large macrophages, are major effectors of innate immunity in the lung. We postulated that HIV-1 impairs pulmonary innate immunity through impairment o...

  12. Evaluation of Inflammatory Cytokine Secretion by Human Alveolar Macrophages

    Directory of Open Access Journals (Sweden)

    J. E. Losa García

    1999-01-01

    Full Text Available The alveolar macrophage (AM secretes interleukin 1β (IL-1β, tumour necrosis factor-α (TNF-α, interleukin-6 (IL-6 and interleukin-8 (IL-8, all of them inflammatory cytokines involved in the pathogenesis of many lung diseases. The aim of the present work was to evaluate the basal and stimulated secretion of these cytokines by human AMs. Human AMs were collected by bronchoalveolar lavage (BAL from four healthy controls and 13 patients with diffuse interstitial lung disease (five cases of sarcoidosis, three of hypersensitivity pneumonitis and five of idiopathic pulmonary fibrosis. AMs were cultured in the presence or absence of different concentrations of lipopolysaccharide (LPS, phorbolmyristate and gammainterferon. IL-1β, TNF-α, IL-6 and IL-8 levels were measured in BAL fluid and culture supernatant using specific enzyme-linked immunosorbent assays. The substance found to stimulate the secretion of inflammatory cytokines to the greatest extent was LPS at a concentration of 10 μg/ml. Regarding the secretion of IL-1β, four observations were of interest: basal secretion was very low; LPS exerted a potent stimulatory effect; considerable within-group variability was observed; and there were no significant differences in the comparisons among groups. With respect to TNF-α secretion, the results were similar. The only striking finding was the higher basal secretion of this cytokine with respect to that of IL-1β. Regarding the secretion of IL-6, the same pattern followed by TNF-α was found. However, it should be stressed that the increase induced by LPS was smaller than in the two previous cytokines. Regarding the secretion of IL-8, three findings were patent: the strong basal secretion of this cytokine; the moderate increase induced by LPS; and the existence of significant differences among the different groups with respect to the stimulated secretion of this cytokine, which reached maximum values in patients with idiopathic pulmonary

  13. STIMULATION OF OXIDANT PRODUCTION IN ALVEOLAR MACROPHAGES BY POLLUTANT AND LATEX PARTICLES

    Science.gov (United States)

    Air pollutant dusts as well as chemically defined particles were examined for their activating effect on oxidant production (O2- and H2O2) in guinea pig alveolar macrophages (AM). Oxidant production was measured as chemiluminescence of albumin-bound luminol. All particles examine...

  14. Enhanced alveolar monocytic phagocyte (macrophage) proliferation in tobacco and marijuana smokers

    Energy Technology Data Exchange (ETDEWEB)

    Barbers, R.G.; Evans, M.J.; Gong, H. Jr.; Tashkin, D.P. (Univ. of California-Los Angeles School of Medicine (USA))

    1991-05-01

    We tested the hypothesis that enhanced cell division accounted for the augmented numbers of monocytic phagocytes with characteristics attributed to alveolar macrophages (AM) found in the lungs of habitual tobacco (T) and marijuana (M) smokers. The monocytic phagocytes, that is, alveolar macrophages, were obtained by bronchoalveolar lavage (BAL) from 12 nonsmoking subjects; 10 subjects who smoked T only (TS); 13 subjects who smoked M only (MS); and 6 smokers of both T and M (MTS). The replication of these cells was determined by measuring the incorporation of ({sup 3}H)thymidine into the DNA of dividing cells and visually counting 2,000 cells on autoradiographically prepared cytocentrifuge cell preparations. This study demonstrated that the number of ({sup 3}H)thymidine-labeled monocytic phagocytes with characteristics of alveolar macrophages from either TS or MS have a higher proliferative index compared to cells (macrophages) from nonsmokers, p less than 0.05 by one-way ANOVA. The total number of BAL macrophages that are in mitosis in TS (17.90 +/- 4.50 labeled AM x 10(3)/ml) or MTS (10.50 +/- 4.20 labeled AM x 10(3)/ml) are 18- and 10-fold greater, respectively, than the number obtained from nonsmokers (1.01 +/- 0.18 labeled AM x 10(3)/ml). Interestingly, the number of ({sup 3}H)thymidine-labeled macrophages from MS (2.90 +/- 0.66 labeled AM x 10(3)/ml) are also greater than the number obtained from nonsmokers, although this is not statistically significant. The stimulus augmenting alveolar macrophage replication is as yet unknown but may likely be found in the T or M smoke.

  15. Enhanced alveolar monocytic phagocyte (macrophage) proliferation in tobacco and marijuana smokers

    International Nuclear Information System (INIS)

    We tested the hypothesis that enhanced cell division accounted for the augmented numbers of monocytic phagocytes with characteristics attributed to alveolar macrophages (AM) found in the lungs of habitual tobacco (T) and marijuana (M) smokers. The monocytic phagocytes, that is, alveolar macrophages, were obtained by bronchoalveolar lavage (BAL) from 12 nonsmoking subjects; 10 subjects who smoked T only (TS); 13 subjects who smoked M only (MS); and 6 smokers of both T and M (MTS). The replication of these cells was determined by measuring the incorporation of [3H]thymidine into the DNA of dividing cells and visually counting 2,000 cells on autoradiographically prepared cytocentrifuge cell preparations. This study demonstrated that the number of [3H]thymidine-labeled monocytic phagocytes with characteristics of alveolar macrophages from either TS or MS have a higher proliferative index compared to cells (macrophages) from nonsmokers, p less than 0.05 by one-way ANOVA. The total number of BAL macrophages that are in mitosis in TS (17.90 +/- 4.50 labeled AM x 10(3)/ml) or MTS (10.50 +/- 4.20 labeled AM x 10(3)/ml) are 18- and 10-fold greater, respectively, than the number obtained from nonsmokers (1.01 +/- 0.18 labeled AM x 10(3)/ml). Interestingly, the number of [3H]thymidine-labeled macrophages from MS (2.90 +/- 0.66 labeled AM x 10(3)/ml) are also greater than the number obtained from nonsmokers, although this is not statistically significant. The stimulus augmenting alveolar macrophage replication is as yet unknown but may likely be found in the T or M smoke

  16. Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages

    Directory of Open Access Journals (Sweden)

    Liao Chung-Ping

    2010-04-01

    Full Text Available Abstract Background Pneumocystis pneumonia is a common opportunistic disease in AIDS patients. The alveolar macrophage is an important effector cell in the clearance of Pneumocystis organisms by phagocytosis. However, both the number and phagocytic activity of alveolar macrophages are decreased in Pneumocystis infected hosts. To understand how Pneumocystis inactivates alveolar macrophages, Affymetrix GeneChip® RG-U34A DNA microarrays were used to study the difference in global gene expression in alveolar macrophages from uninfected and Pneumocystis carinii-infected Sprague-Dawley rats. Results Analyses of genes that were affected by Pneumocystis infection showed that many functions in the cells were affected. Antigen presentation, cell-mediated immune response, humoral immune response, and inflammatory response were most severely affected, followed by cellular movement, immune cell trafficking, immunological disease, cell-to-cell signaling and interaction, cell death, organ injury and abnormality, cell signaling, infectious disease, small molecular biochemistry, antimicrobial response, and free radical scavenging. Since rats must be immunosuppressed in order to develop Pneumocystis infection, alveolar macrophages from four rats of the same sex and age that were treated with dexamethasone for the entire eight weeks of the study period were also examined. With a filter of false-discovery rate less than 0.1 and fold change greater than 1.5, 200 genes were found to be up-regulated, and 144 genes were down-regulated by dexamethasone treatment. During Pneumocystis pneumonia, 115 genes were found to be up- and 137 were down-regulated with the same filtering criteria. The top ten genes up-regulated by Pneumocystis infection were Cxcl10, Spp1, S100A9, Rsad2, S100A8, Nos2, RT1-Bb, Lcn2, RT1-Db1, and Srgn with fold changes ranging between 12.33 and 5.34; and the top ten down-regulated ones were Lgals1, Psat1, Tbc1d23, Gsta1, Car5b, Xrcc5, Pdlim1, Alcam

  17. The effects of clofibrate ingestion on alveolar macrophage peroxisome content and oxygen metabolism.

    Science.gov (United States)

    Drath, D B; Davies, P; Shorrey, J M; Simpson, P

    1982-07-01

    Respiratory burst activity in alveolar macrophages in response to particulate and soluble challenges, such as zymosan particles and phorbol myristate acetate (PMA), is not nearly as dependent upon membrane stimulation as in neutrophils. Microperoxisomes are subcellular organelles containing catalase and are present in lung macrophages and cells of other organs. Evidence from liver cells indicates that peroxisomes are intimately involved with hydrogen peroxide and lipid metabolism. Clofibrate (2-(p-chlorophenoxy)-2-methylpropionic acid ethyl, Atromid-S-), a hypolipidemic drug known to cause peroxisomal proliferation in liver cells, was studied with respect to its ability to cause increases in the microperoxisome content and to alter the cellular metabolism of alveolar macrophages. Liver weight increased over a 2-week drug treatment period while lung weight remained unchanged. Plasma triglyceride levels were decreased by the treatment, indicating the effectiveness of the drug. Unlike the effect on liver cells, however, clofibrate did not cause a proliferation of microperoxisomes, as determined by morphometric analysis. Oxygen consumption and hydrogen peroxide generation by alveolar macrophages in response to either stimulant (zymosan or PMA) was no greater in clofibrate-treated rats than in controls. Superoxide release, when expressed as the change in response to PMA, appeared elevated in the drug group; statistical significance, however, was not demonstrated. The hexose monophosphate shunt (HMP), which produces reducing equivalents for lipid biosynthesis, was elevated in macrophages from clofibrate-treated rats when expressed similarly. The significance of these results in relation to the known effects of the drug on liver cells. PMID:6291347

  18. [Corticosterone reception by alveolar macrophages when their functional activity has changed].

    Science.gov (United States)

    Shishkina, L N; Maianskiĭ, D N; Shutko, G V; Sergeev, P V

    1985-01-01

    The binding of 3H-corticosterone by rat alveolar macrophages was studied before and after stimulation with zymosan in vivo. Thirty min after incubation of the macrophagal monolayer from intact animals with 3H-corticosterone accumulation of the hormone by the cells came to an end. As the concentration of 3H-corticosterone in the incubation medium was raised, the binding of the hormone with the saturated (receptor) system of alveolar macrophages terminated upon absorption of 10.6 fmol per 10(6) cells. Further raising of the level of the bound hormone was effected by the unsaturated (lipid) system. Stimulation with zymosan led not only to an increase in the number of the cells of the bronchoalveolar tract but also to an elevation of the intensity of 3H-corticosterone engulfment by alveolar macrophages. The number of binding sites per cell in the zymosan-activated macrophages increased 1.5-fold. This may be an important moment determining the development and liquidation of mononuclear infiltrations in the lung. PMID:3967077

  19. Peroxidatic activity distinct from myeloperoxidase in human monocytes cultured in vitro and in alveolar macrophages.

    Science.gov (United States)

    Breton-Gorius, J; Vildé, J L; Guichard, J; Vainchenker, W; Basset, F

    1982-01-01

    Human monocytes develop a peroxidatic activity (PA) in rough endoplasmic reticulum (RER) after adherence or after culture in semi-solid medium. This enzyme activity disappears after three days of culture in the majority of macrophages derived from adult monocytes but persists for one week in macrophages derived from neonatal monocytes. The PA is due to an enzyme distinct from myeloperoxidase (MPO), since monocytes from a patient with MPO deficiency develop the same PA as that of normal monocytes after adherence. By its localization and other characteristics, PA of adherent monocytes resembles that of rodent macrophages. We therefore investigated whether human alveolar macrophages exhibit PA, using a sensitive cytochemical method which prevents inhibition by aldehyde in adherent monocytes. In various pathological cases, four types of macrophages could be identified: the majority were peroxidase-negative, a small percentage was of exudate type exhibiting a PA in granules as blood monocytes, while few macrophages were intermediate, possessing only PA in RER i.e. of type resident and a smaller proportion had PA in RER and in granules i.e. exudate-resident macrophages. These findings demonstrate that human macrophages and adherent monocytes may exhibit PA in RER as has been reported for rodent macrophages. The true nature and function of the enzyme responsible for this PA, which is distinct from MPO, remains unknown, but some arguments seem to suggest its role in prostaglandin synthesis. PMID:6283838

  20. The effect of tobacco smoke on the metabolism and function of rat alveolar macrophages.

    Science.gov (United States)

    Drath, D B; Harper, A; Gharibian, J; Karnovsky, M L; Huber, G L

    1978-04-01

    Alveolar macrophages harvested by bronchopulmonary lavage from rats exposed to tobacco smoke for 30 days ("smokers") showed alterations in oxidative metabolism, lactate production and phagocytosis of inert starch particles when compared with control macrophages. Phagocytosis of viable Staphylococcus aureus was unaffected by tobacco smoke. Glucose oxidation measured by conversion of glucose-1-14C to 14CO2 moderately affected while oxidation of glucose-6-14C to 14CO2 was not. Smokers routinely yielded fewer cells than controls, though these cells contained approximately 17% more protein than did controls. Opsonization of particles was not necessary for macrophages from either smoker or control animals to manifest a respiratory burst and increased superoxide and hydrogen peroxide release during phagocytosis. The glycolytic inhibitors, sodium fluoride and iodoacetamide, while effectively blocking glycolysis, did not inhibit phagocytosis by macrophages from either group. The results reported clearly distinguish alveolar macrophages from other phagocytic cells (peritoneal macrophages and polymorphonuclear leukocytes) and suggest a state of non-specific activation caused by exposure to tobacco smoke. PMID:205549

  1. Mesenchymal stem cells alleviate experimental asthma by inducing polarization of alveolar macrophages.

    Science.gov (United States)

    Song, Xiaolian; Xie, Shuanshuan; Lu, Kun; Wang, Changhui

    2015-04-01

    The reparative and immunoregulatory properties of mesenchymal stromal cells (MSCs) have made them attractive candidates for cellular therapy. However, the underlying mechanism of the effects of transplanted MSCs on allergic asthma remains elusive. Here, we show that administration of MSCs isolated from human bone marrow provoked a pronounced polarization in alveolar macrophages to M2 subtypes, rather than induced an increase in the total macrophage number, and efficiently inhibited hallmark features of asthma, including airway hyperresponsiveness and eosinophilic accumulation. Moreover, transforming growth factor beta (TGF-β) signaling pathway appeared to mediate the effects of MSCs on macrophage polarization and subsequently the inhibition of hallmark features of asthma. Inhibition of TGF-β signaling was sufficient to inhibit the macrophage polarization in response to MSCs and consequently reserved the inhibitory effects of macrophage polarization on hallmark features of asthma. Collectively, our data demonstrate that human MSCs have immunosuppressive activity on asthma, which is mediated by TGF-β-signaling-dependent alveolar macrophage polarization. PMID:24958014

  2. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    International Nuclear Information System (INIS)

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO2 or different isotopic compositions (70% or 97% 239Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO2-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% 239Pu than for 70% 239Pu. (authors)

  3. Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Tourdes, F.; Gremy, O.; Grillon, G.; Abram, M.C.; Poncy, J.L.; Griffiths, N. [CEA, DSV, DRR, SRCA, Centre DAM Ile de France, F-91297 Bruyeres Le Chatel, Arpajon (France)

    2008-07-01

    Alveolar macrophages play an important role in the distribution, clearance and inflammatory reactions after particle inhalation, which may influence long-term events such as fibrosis and tumorigenesis. The objectives of the present study were to investigate the early inflammatory events after plutonium oxide inhalation in rats and involvement of alveolar macrophages. Lung changes were studied from 3 days to 3 months after inhalation of PuO{sub 2} or different isotopic compositions (70% or 97% {sup 239}Pu) and initial lung deposits (range 2.1 to 43.4 kBq/rat). Analyses of bronchoalveolar lavages showed early increases in the numbers of granulocytes, lymphocytes and multi-nucleated macrophages. The activation of macrophages was evaluated ex vivo by measurement of inflammatory mediator levels in culture supernatants. TNF-alpha and chemokine MCP-1, MIP-2 and CINC-1 production was elevated from 7 days after inhalation and remained so up to 3 months. In contrast, IL-1 beta, IL-6 and IL-10 production was unchanged. At 6 weeks, pulmonary macrophage numbers and activation state were increased as observed from an immunohistochemistry study of lung sections with anti-ED1. Similarly, histological analyses of lung sections also showed evidence of inflammatory responses. In conclusion, our results indicate early inflammatory changes in the lungs of PuO{sub 2}-contaminated animals and the involvement of macrophages in this process. A dose-effect relationship was observed between the amount of radionuclide inhaled or retained at the time of analysis and inflammatory mediator production by alveolar macrophages 14 days after exposure. For similar initial lung deposits, the inflammatory manifestation appears higher for 97% {sup 239}Pu than for 70% {sup 239}Pu. (authors)

  4. Carbon black nanoparticles induce type II epithelial cells to release chemotaxins for alveolar macrophages

    Directory of Open Access Journals (Sweden)

    Donaldson Ken

    2005-12-01

    Full Text Available Abstract Background Alveolar macrophages are a key cell in dealing with particles deposited in the lungs and in determining the subsequent response to that particle exposure. Nanoparticles are considered a potential threat to the lungs and the mechanism of pulmonary response to nanoparticles is currently under intense scrutiny. The type II alveolar epithelial cell has previously been shown to release chemoattractants which can recruit alveolar macrophages to sites of particle deposition. The aim of this study was to assess the responses of a type II epithelial cell line (L-2 to both fine and nanoparticle exposure in terms of secretion of chemotactic substances capable of inducing macrophage migration. Results Exposure of type II cells to carbon black nanoparticles resulted in significant release of macrophage chemoattractant compared to the negative control and to other dusts tested (fine carbon black and TiO2 and nanoparticle TiO2 as measured by macrophage migration towards type II cell conditioned medium. SDS-PAGE analysis of the conditioned medium from particle treated type II cells revealed that a higher number of protein bands were present in the conditioned medium obtained from type II cells treated with nanoparticle carbon black compared to other dusts tested. Size-fractionation of the chemotaxin-rich supernatant determined that the chemoattractants released from the epithelial cells were between 5 and 30 kDa in size. Conclusion The highly toxic nature and reactive surface chemistry of the carbon black nanoparticles has very likely induced the type II cell line to release pro-inflammatory mediators that can potentially induce migration of macrophages. This could aid in the rapid recruitment of inflammatory cells to sites of particle deposition and the subsequent removal of the particles by phagocytic cells such as macrophages and neutrophils. Future studies in this area could focus on the exact identity of the substance(s released by the

  5. IL-1α induces CD11b(low) alveolar macrophage proliferation and maturation during granuloma formation.

    Science.gov (United States)

    Huaux, François; Lo Re, Sandra; Giordano, Giulia; Uwambayinema, Francine; Devosse, Raynal; Yakoub, Yousof; Panin, Nadtha; Palmai-Pallag, Mihaly; Rabolli, Virginie; Delos, Monique; Marbaix, Etienne; Dauguet, Nicolas; Couillin, Isabelle; Ryffel, Bernhard; Renauld, Jean-Christophe; Lison, Dominique

    2015-04-01

    Macrophages play a central role in immune and tissue responses of granulomatous lung diseases induced by pathogens and foreign bodies. Circulating monocytes are generally viewed as central precursors of these tissue effector macrophages. Here, we provide evidence that granulomas derive from alveolar macrophages serving as a local reservoir for the expansion of activated phagocytic macrophages. By exploring lung granulomatous responses to silica particles in IL-1-deficient mice, we found that the absence of IL-1α, but not IL-1β, was associated with reduced CD11b(high) phagocytic macrophage accumulation and fewer granulomas. This defect was associated with impaired alveolar clearance and resulted in the development of pulmonary alveolar proteinosis (PAP). Reconstitution of IL-1α(-/-) mice with recombinant IL-1α restored lung clearance functions and the pulmonary accumulation of CD11b(high) phagocytic macrophages. Mechanistically, IL-1α induced the proliferation of CD11b(low) alveolar macrophages and differentiated these cells into CD11b(high) macrophages which perform critical phagocytic functions and organize granuloma. We newly discovered here that IL-1α triggers lung responses requiring macrophage proliferation and maturation from tissue-resident macrophages. PMID:25421226

  6. Intracellular pathogens within alveolar macrophages in a patient with HIV infection: diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Takashi Shinha

    2015-03-01

    Full Text Available In HIV-infected individuals, macrophages, the key defense effector cells, manifest defective activity in their interactions with a wide variety of opportunistic pathogens, including fungi and protozoa. Understanding the morphological characteristics of intracellular opportunistic pathogens in addition to their pathogenesis is of critical importance to provide optimal therapy, thereby decreasing morbidity and mortality in HIV-infected patients. We herein present a case of disseminated histoplasmosis confused with disseminated visceral leishmaniasis in an HIV-infected individual from Guyana who developed intracellular organisms within alveolar macrophages

  7. Alveolar macrophages and lung lesions after combined exposure to nickel, cobalt, and trivalent chromium.

    OpenAIRE

    Johansson, A; Curstedt, T.; Jarstrand, C; Camner, P

    1992-01-01

    In earlier inhalation exposures of rabbits, nickel increased the production of surfactant by type II cells, with secondary effects on morphology and function of alveolar macrophages. Cobalt induced mainly a nodular growth pattern of the type II cells. Trivalent chromium seemed to impair the capacity of macrophages to catabolize surfactant but did not affect the type II cells. We exposed rabbits by inhalation to combinations of nickel (0.6 mg/m3 as NiCl2) and trivalent chromium [1.2 mg/m3 as C...

  8. Role of alveolar macrophages in the dissolution of two different industrial uranium oxides.

    Science.gov (United States)

    Hengé-Napoli, M H; Ansoborlo, E; Claraz, M; Berry, J P; Cheynet, M C

    1996-05-01

    This study was aimed at assessing and understanding some mechanisms involved in the intracellular particle transformation of two uranium oxides (U3O8 and UO2 + Umetal) produced by a new isotopic enrichment plant using laser technology. Instillations were conducted on rats with both uranium compounds and alveolar macrophages were harvested at different dates and prepared in order to be studied using transmission electron microscopy and electron energy loss spectrometry (EELS). The presence of particles in the cells was observed from the first day after instillation, and crystalline needles of uranyl phosphate appeared in the cytoplasm of the cells. These needles were more numerous after instillation with the mixture UO2 + Umetal than after administration of U3O8 and may be correlated with the higher solubility of UO2 + Umetal observed in vitro. The formation of insoluble needles in lysosomes is consistent with the insolubilisation of uranium observed after phagocytosis by alveolar macrophages. PMID:8793194

  9. Decreased Apoptotic Rate of Alveolar Macrophages of Patients with Idiopathic Pulmonary Fibrosis

    OpenAIRE

    Fotios Drakopanagiotakis; Areti Xifteri; Evaggelos Tsiambas; Andreas Karameris; Konstantina Tsakanika; Napoleon Karagiannidis; Demetrios Mermigkis; Vlasis Polychronopoulos; Demosthenes Bouros

    2012-01-01

    Introduction. Increased apoptosis of epithelial cells and decreased apoptosis of myofibroblasts are involved in the pathogenesis of IPF. The apoptotic profile of alveolar macrophages (AMs) in IPF is unclear. Aim. To investigate whether AMs of patients with IPF exhibit a different apoptotic profile compared to normal subjects. Methods. We analyzed, by immunohistochemistry, the expression of the apoptotic markers fas, fas ligand , bcl-2, and bax in AM obtained from bronchoalveolar lavage fluid ...

  10. COMPARISON OF CONDITIONING REGIMENS FOR ALVEOLAR MACROPHAGE RECONSTITUTION AND INNATE IMMUNE FUNCTION POST BONE MARROW TRANSPLANT

    OpenAIRE

    Hubbard, Leah L. N.; Ballinger, Megan N.; Wilke, Carol A.; Moore, Bethany B.

    2008-01-01

    The authors compared efficiency of alveolar macrophage (AM) reconstitution from donor bone marrow post transplant following 4 chemotherapy conditioning regimens and 2 total body irradiation (TBI) regimens. TBI regimens are more effective in inducing AM reconstitution from donor marrow. However, mice conditioned with 13 Gy split-dose TBI or a dual-chemotherapy regimen (25 mg/kg busulfan × 4 days plus cyclophosphamide 100 mg/kg × 2 days) both demonstrate significant AM repopulation from donor m...

  11. Study of changes in cellular surface glycoproteins of alveolar macrophages in fibrotic lung disorders

    Directory of Open Access Journals (Sweden)

    J McClure

    2006-04-01

    Full Text Available Introduction: The respiratory system is both a route of entry and exit for toxins and injurious agents, as well as being a target for chemical substances and pathogens. Therefore, an understanding of the structure and function of the migratory cell populations of pulmonary tissues including alveolar macrophages is central in a number of important disease processes. This study aimed to identify and specify the glycotypes of alveolar macrophages in fibrotic lung disorders. Methods: Sections of paraffin-embedded tissue from 40 cases in both normal human lung and fibrotic lung disorders were studied by immunohistology and by lectin histochemistry with a panel of 27 biotinylated lectins. Results: The findings of this study showed that ten lectins (AHA, PTL-II, AAA, , LTA, UEA-I, BSA-1B4, VVA, SBA, DBA, PTL-I did not bind to the alveolar macrophages in any of the cases, whereas 17 lectins (GNA, NPA, HHA, l-PHA, e-PHA, LCA, PSA, ConA, LEA, PAA, s-WGA, ECA, MPA,HPA, WFA, SNA, MAA( bound from moderately to strongly. In contrast, in fibrotic lung disorders some glycans were somewhat more marked or changed. Conclusion: Glycans terminating in -galactose, terminal Gal1,3GalNAc and subsets of GalNAc also appeared in alveolar macrophages of fibrotic lung disorders. L-fucosylated and terminal -linked galactosyl glycans were also detected in diseases states. Subsets of N-glycans were either changed minimally or not at all.

  12. Decreased leukotriene B4 synthesis in smokers' alveolar macrophages in vitro.

    OpenAIRE

    Laviolette, M.; Coulombe, R; Picard, S.; Braquet, P; Borgeat, P

    1986-01-01

    Recent studies have shown that alveolar macrophages (AM) are able to release leukotrienes (LTs). Since cigarette smoking inhibits the cyclooxygenase pathway of arachidonic acid metabolism in the AM, we evaluated the LT production by AM from smokers and nonsmokers. AM were obtained from 35 volunteers, 16 nonsmokers, and 19 smokers. The cells were incubated under various conditions including stimulation with 30 microM arachidonic acid, 2 microM ionophore A23187, or both. Each experiment was per...

  13. Alveolar macrophages and lung surfactant in the defense against Cryptococcus neoformans

    OpenAIRE

    Gross, Norma Teresa

    2000-01-01

    Cryptococcus neoformans causes disease mainly in immunosuppressed patients, especially those with AIDS, and on corticosteroids. The yeast is normally inhaled and the lung is the primary site of infection, where the alveolar macrophages (AM) provide a first line of host defense. The aim of this thesis was to study immune responses of AM and immunomodulatory functions of lung surfactant phospholipids in the defense against C. neoformans, using the rat or rabbit as animal model...

  14. Benzo(a)pyrene activation and detoxification by human pulmonary alveolar macrophages and lymphocytes

    International Nuclear Information System (INIS)

    Comparisons of pulmonary alveolar macrophages and circulating lymphocytes from five smokers and five nonsmokers for their ability to metabolize benzo(a)pyrene as determined by high pressure liquid chromatography were carried out. Utilizing this approach, further investigation of activation and detoxification by several human cell types could provide the basis for more precise and comprehensive studies of carcinogen and drug metabolism in the human lung, and for a better assessment of cancer risk in selected populations

  15. Alveolar macrophages modulate allergic inflammation in a murine model of asthma

    OpenAIRE

    Bang, Bo-Ram; Chun, Eunyoung; Shim, Eun-Jin; Lee, Hyun-Seung; Lee, Soo-Yeon; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Park, Heung-Woo

    2011-01-01

    The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Pheno...

  16. Different pathways of degradation of SP-A and saturated phosphatidylcholine by alveolar macrophages.

    Science.gov (United States)

    Baritussio, A; Alberti, A; Armanini, D; Meloni, F; Bruttomesso, D

    2000-07-01

    Alveolar macrophages degrade surfactant protein (SP) A and saturated phosphatidycholine [dipalmitoylphosphatidylcholine (DPPC)]. To clarify this process, using rabbit alveolar macrophages, we analyzed the effect of drugs known to affect phagocytosis, pinocytosis, clathrin-mediated uptake, caveolae, the cytoskeleton, lysosomal pH, protein kinase C, and phosphatidylinositol 3-kinase (PI3K) on the degradation of SP-A and DPPC. We found the following: 1) SP-A binds to the plasma membrane, is rapidly internalized, and then moves toward degradative compartments. Uptake could be clathrin mediated, whereas phagocytosis, pinocytosis, or the use of caveolae are less likely. An intact cytoskeleton and an acidic milieu are necessary for the degradation of SP-A. 2) Stimulation of protein kinase C increases the degradation of SP-A. 3) PI3K influences the degradation of SP-A by regulating both the speed of internalization and subsequent intracellular steps, but its inhibition does not prevent SP-A from reaching the lysosomal compartment. 4) The degradation of DPPC is unaffected by most of the treatments able to influence the degradation of SP-A. Thus it appears that DPPC is degraded by alveolar macrophages through mechanisms very different from those utilized for the degradation of SP-A. PMID:10893207

  17. Transcription analysis of the porcine alveolar macrophage response to Mycoplasma hyopneumoniae.

    Directory of Open Access Journals (Sweden)

    Li Bin

    Full Text Available Mycoplasma hyopneumoniae is considered the major causative agent of porcine respiratory disease complex, occurs worldwide and causes major economic losses to the pig industry. To gain more insights into the pathogenesis of this organism, the high throughput cDNA microarray assays were employed to evaluate host responses of porcine alveolar macrophages to M. hyopneumoniae infection. A total of 1033 and 1235 differentially expressed genes were identified in porcine alveolar macrophages in responses to exposure to M. hyopneumoniae at 6 and 15 hours post infection, respectively. The differentially expressed genes were involved in many vital functional classes, including inflammatory response, immune response, apoptosis, cell adhesion, defense response, signal transduction, protein folding, protein ubiquitination and so on. The pathway analysis demonstrated that the most significant pathways were the chemokine signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway, nucleotide-binding oligomerization domains (Nod-like receptor signaling pathway and apoptosis signaling pathway. The reliability of the data obtained from the microarray was verified by performing quantitative real-time PCR. The expression kinetics of chemokines was further analyzed. The present study is the first to document the response of porcine alveolar macrophages to M. hyopneumoniae infection. The data further developed our understanding of the molecular pathogenesis of M. hyopneumoniae.

  18. Degradation of rat pulmonary surfactant disaturated phosphatidylcholines (DSPC) by alveolar macrophages

    International Nuclear Information System (INIS)

    Experiments were carried out to determine the fate of pulmonary surfactant DSPC when it is incubated in vitro with alveolar macrophages. Rats were injected (i.v.) with 3H-choline, sacrificed 22 hours later, and surfactant materials (sam) containing labeled DSPC were obtained by lung lavage and purified with NaBr density gradients. The sam was incubated in phosphate-buffered medium (containing 1.8 mM Ca2+ and 1.0 mM Mg2+) with alveolar macrophages from unlabeled animals. During incubation with cells for six hours, the labeled DSPC disappears along a time course which is most rapid between two and four hours. The labeled sam DSPC does not disappear when incubated without cells. A plot of the amount of DSPC broken down vs the sam DSPC concentration indicates that the process displays saturation kinetics. The specific activity of the DSPC in the incubation mixture does not change over six hours, suggesting that the breakdown products are not reutilized by the cells, at least during this time period. All of the label which disappears from the DSPC appears as water-soluble choline products. No lysophosphatidylcholines are formed. When the cells are incubated with dipalmitoylphosphatidylcholine (DPPC) vesicles, there is degradation of the DPPC which is approximately 50% of the breakdown which occurs with sam DSPC. These results suggest that surfactant DSPC can be degraded by alveolar macrophages

  19. Plutonium behavior after pulmonary administration according to solubility properties, and consequences on alveolar macrophage activation.

    Science.gov (United States)

    Van der Meeren, Anne; Gremy, Olivier; Renault, Daniel; Miroux, Amandine; Bruel, Sylvie; Griffiths, Nina; Tourdes, Françoise

    2012-01-01

    The physico-chemical form in which plutonium enters the body influences the lung distribution and the transfer rate from lungs to blood. In the present study, we evaluated the early lung damage and macrophage activation after pulmonary contamination of plutonium of various preparation modes which produce different solubility and distribution patterns. Whatever the solubility properties of the contaminant, macrophages represent a major retention compartment in lungs, with 42 to 67% of the activity from broncho-alveolar lavages being associated with macrophages 14 days post-contamination. Lung changes were observed 2 and 6 weeks post-contamination, showing inflammatory lesions and accumulation of activated macrophages (CD68 positive) in plutonium-contaminated rats, although no increased proliferation of pneumocytes II (TTF-1 positive cells) was found. In addition, acid phosphatase activity in macrophages from contaminated rats was enhanced 2 weeks post-contamination as compared to sham groups, as well as inflammatory mediator levels (TNF-α, MCP-1, MIP-2 and CINC-1) in macrophage culture supernatants. Correlating with the decrease in activity remaining in macrophages after plutonium contamination, inflammatory mediator production returned to basal levels 6 weeks post-exposure. The production of chemokines by macrophages was evaluated after contamination with Pu of increasing solubility. No correlation was found between the solubility properties of Pu and the activation level of macrophages. In summary, our data indicate that, despite the higher solubility of plutonium citrate or nitrate as compared to preformed colloids or oxides, macrophages remain the main lung target after plutonium contamination and may participate in the early pulmonary damage.

  20. Metabolic and functional characteristics of alveolar macrophages recovered from rats exposed to marijuana smoke.

    Science.gov (United States)

    Drath, D B; Shorey, J M; Price, L; Huber, G L

    1979-07-01

    Pulmonary alveolar macrophages were obtained by bronchopulmonary lavage from male rats after 30 consecutive days of in vivo exposure to marijuana and tobacco smoke. No significant differences were found between either group of experimental animals and controls in the number of cells recovered, the protein content per 10(6) cells, or the percentage of cells that adhered to plastic surfaces. The ability of macrophages to phagocytize viable bacteria was not affected by exposure to either marijuana or tobacco smoke in that both treatment groups ingested Staphylococcus aureus over a 60-min period as well as did control cells. Differences were found between the groups, however, with respect to cellular metabolism. Marijuana smoke inhalation caused a small decrease in the amount of oxygen consumed by macrophages during phagocytosis, as compared with control cells. This may have been reflected in the even greater decrease in superoxide formation observed during particle engulfment by these treated cells. Tobacco smoke, on the other hand, increased oxygen consumption and was without effect on superoxide release. Neither tobacco nor marijuana smoke treatment had an effect on the direct oxidation of glucose via the hexose monophosphate shunt. Our results indicate that, despite several metabolic alterations in response to marijuana and tobacco smoke, alveolar macrophages were not compromised with respect to their ability to ingest a particulate challenge. PMID:225274

  1. Response of perifused alveolar macrophages to glass fibers: effect of exposure duration and fiber length

    International Nuclear Information System (INIS)

    The effect of glass fibers on rat alveolar macrophages was studied with a new perifusion technique which allows the sequential determination of cell-derived inflammatory mediators as well as estimation of cell viability and aggregation at the end of the incubation period. Results showed that glass fibers induced dose-dependent release of prostaglandins and B-glucuronidase from macrophages and the aggregation and death of these cells. These deleterious effects were clearly related to the length of the fibers, with the longer fibers (greater than or equal to4-5 μm) being more active than the shorter ones (<3 μm). Furthermore, a short exposure of 1 hr followed by an 18-hr perifusion induced the same inflammatory and toxic effects on the macrophages as did leaving the fibers undisturbed for the complete 18-hr perifusion. Measurement of prostaglandins was performed by radioimmunoassay. It is concluded that glass fibers produce effects in cultures of rat alveolar macrophages qualitatively similar to those of asbestos, and that fiber length appears to be a critical determinant of toxicity

  2. Involvement of NF-¿B and MAP-kinases in the transcriptional response of alveolar macrophages to Streptococcus suis

    NARCIS (Netherlands)

    Greeff, de A.; Benga, A.; Wichgers, P.J.; Valentin-Weigand, P.; Rebel, J.M.J.; Smith, H.E.

    2010-01-01

    Interaction of Streptococcus suis with primary porcine alveolar macrophages was Studied using transcriptomics. Transcriptional response of macrophages to two different S. suis strains was studied: wild-type S10 that is resistant to phagocytosis, and its non-encapsulated mutant that is phagocytosed e

  3. Role of alveolar macrophages in dissemination of Marek’s disease virus from lungs to lymphoid organs

    Science.gov (United States)

    To understand the specific role of macrophages in the control or exacerbation of Marek’s disease (MD), alveolar macrophages of chickens were depleted by intra-tracheal (IT) instillation of Cl2MBP. Forty-eight hours post treatment chicks were inoculated with 100 micro liter of cell-free MD virus (MD...

  4. Upregulation of platelet-derived growth factor-A and -B gene expression in alveolar macrophages of individuals with idiopathic pulmonary fibrosis.

    OpenAIRE

    Nagaoka, I; Trapnell, B C; Crystal, R G

    1990-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by accumulation of alveolar macrophages spontaneously releasing exaggerated amounts of the potent mesenchymal cell growth factor platelet-derived growth factor (PDGF). To evaluate the relative contribution of the two PDGF genes to this process, PDGF-A and -B gene transcription rates and mRNA levels were examined in normal and IPF alveolar macrophages. While normal alveolar macrophages constitutively transcribe both PDGF-A and PDGF-B genes, ...

  5. Formulation and characterization of pyrazinamide polymeric nanoparticles for pulmonary tuberculosis: Efficiency for alveolar macrophage targeting

    Directory of Open Access Journals (Sweden)

    J N Ravi Varma

    2015-01-01

    Full Text Available Pyrazinamide, a highly specific agent against Mycobacterium tuberculosis is used as first-line drug to treat tuberculosis. The current work aims to formulate polymeric nanoparticles based drug delivery system to sustain the release profile and reduce the dosing frequency of pyrazinamide. Further aim was to target the macrophages within body fluid. These polymeric nanoparticles were prepared by simultaneous double-emulsion (W/O/W solvent evaporation/diffusion technique. The prepared dispersions were characterized for various biopharmaceutical parameters such as particle size, zeta potential, polydispersity index, drug loading capacity, entrapment efficiency and targeting to alveolar macrophages. The formulated polymeric nanoparticles were in the particle size range of 45.51 to 300.4 nm with a maximum drug entrapment efficiency of 80.9%. The stability study of optimized batch conducted at 40±2°/75±5% relative humidity showed no significant changes up to 90 days. X-Ray Diffraction spectrum exhibits the transformation of crystalline form of drug to amorphous in the formulation. Scanning Electron Microscope image showed nanoparticles spherical in shape with smooth surface. In vitro release profiles were biphasic in nature with burst release followed by controlled release over a period of 24 h obeying diffusion mechanism. In vivo and ex vivo studies results of the study show significant uptake of the nanoparticles by alveolar macrophages through fluorescent micrograph. Polymeric nanoparticles formulation of pyrazinamide could encompass significant uptake by alveolar macrophages, the high first-pass metabolism, sustain the release of drug leading to reduction in dose, toxicity and improvement of patient compliance.

  6. Toxicity of penicillic acid for rat alveolar macrophages in vitro

    International Nuclear Information System (INIS)

    Penicillic acid (PA) is a polyketide mycotoxin produced by several species of Aspergillus and Penicillium. This mycotoxin is toxic in experimental animals and has also been reported to be carcinogenic. The cytotoxicity of penicillic acid was studied in rat albeolar macrophages (AM) in vitro. The effects of penicillic acid on membrane integrity were studied by measuring cell volume changes and 51Cr release. There was a significant decrease in adenosine triphosphate (ATP) in cell cultures exposed to 1.0 mM penicillic acid for 4 hr. Inhibition of the incorporation of [3H]leucine into protein was both dose- and time-dependent and protein synthesis was inhibited significantly after 2 hr exposure to ≥0.1 mM penicillic acid. RNA synthesis was inhibited to a lesser extent than protein synthesis. There was significant inhibition of phagocytosis after 2 hr exposure at ≥0.3 mM penicillic acid and the ED50 for phagocytosis was 0.09 mM. Thus phagocytosis was more sensitive to the toxic effects of penicillic acid than any other cellular process studied. The data suggest the possibility of a respiratory hazard to agricultural workers exposed to contaminated grain

  7. Synthesis of lyso(bis)phosphatidic acid in rabbit alveolar macrophages

    International Nuclear Information System (INIS)

    Reported here are studies on the biosynthetic pathway used by normal and BCG elicited alveolar macrophages for the synthesis of lyso(bis)phosphatidic acid [L(bis)PA]. Earlier observations by this laboratory have shown that although L(bis)PA is abundant in these cells, there is little de novo synthesis of this lipid. Diaceyl phosphatidylglycerol [PG] labeled with either [1,2,3-3H] glycerol or 32P demonstrated that PG is used as an exogenous substrate for L(bis)PA formation; both glycerol moieties are incorporated. Other phospholipids do not have this capacity. BCG-elicited macrophages are capable of only one-quarter the synthesis of L(bis)PA seen with normal cells, and also show a decreased amount of cell associated substrate. In addition, [3H] 1-0-alkyl PG was used as a substrate to test the importance of the sn-1 acyl linkage in the synthetic pathway. This substrate produced less L(bis)PA while dramatically increasing the amounts of labelled phosphatidylethanolamine and phosphatidylcholine within the cell. The alkyl substrate also showed increased uptake by the cell. They conclude that the hydrolysis of the acyl group at the sn-1 position of PG is essential in the synthetic pathway leading to the production of L(bis)PA. They further suggest that the PG used by these cells as an exogenous substrate in vitro is obtained from the PG-rich surfactant surrounding the alveolar macrophage

  8. Functional, biochemical, and morphologic changes in alveolar macrophages following thoracic x-irradiation

    International Nuclear Information System (INIS)

    Alveolar macrophages lavaged from mice at various times after 1800 rads of thoracic x-irradiation were compared to control mice. Determination of their numbers, size distribution, glass adherence, latex particle uptake, cytochemistry, morphology, protein, phospholipid, and hydrolytic enzyme composition showed that defective bacterial uptake and clearance, which has been demonstrated by other workers, may be related to a transient decrease in their numbers rather than activity. A decrease in numbers is explainable on the basis of a population of radiosensitive precursors in the lung interstitium. The work load in the alveolar space may prolong the duration of their residence in the alveoli as well as increase their size and content of hydrolytic enzymes and ingested surfactant components

  9. Milk protein and Oil-red-O staining of alveolar macrophages in chronic respiratory disease of infancy.

    OpenAIRE

    De Baets, Frans; Aarts, Claudia; HAERYNCK, FILOMEEN; Van daele, Sabine; De Wachter, Elke; De Schutter, Iris; Malfroot, Anne; Schelstraete, Petra

    2010-01-01

    Abstract Aspiration is a suspected cause of chronic respiratory disease in infants. We assessed the probability of aspiration by immunocytochemical staining of alveolar macrophages for milk proteins (?-lactalbumin and ?-lactoglobulin) and compared these findings with the Oil-Red-0 staining score. Broncho-alveolar lavage (BAL), 24-hour esophageal pH-measurement and/or gastro-esophageal scintigraphy were performed in 111 children. Seventy nine patients were enrolled. Ten exclu...

  10. Study of possible changes brought about by plutonium oxide in the acid phosphatase activity of alveolar macrophages of the rabbit

    International Nuclear Information System (INIS)

    This report describes the various techniques used for determining the acid phosphatase activity of alveolar rabbit macrophages after inhalation of radioactive plutonium oxide particles, exposure of the animals, removal and sampling of the alveolar cells, and technical dosage. The results obtained are presented; they do not make it possible, in this particular case, to affirm that an important change in the enzymatic activity studied occurs. (author)

  11. Modulation of the effects of alveolar macrophages on lung fibroblast collagen production rate

    International Nuclear Information System (INIS)

    Alveolar macrophages (AM) may function as effector cells that can either stimulate or inhibit lung fibroblast collagen production. However, conditions that determine the predominant effect of AM on fibroblasts are not well understood. To delineate factors that modulate the effects of AM on lung fibroblasts, we studied the interaction of AM products and fibroblasts in vitro. The AM were obtained by bronchoalveolar lavage of hamsters with bleomycin-induced pulmonary fibrosis. Conditioned medium (CM) from the AM cultures was incubated in varying amounts with lung fibroblast (IMR-90) cultures. After metabolic labeling with [3H]proline, fibroblast collagen production based on procollagen-specific radioactivity was determined. Macrophage CM in concentrations greater than 5% suppressed collagen production, an event attributed to the macrophage-derived suppressive factor that we have previously characterized. Macrophages were also determined to produce PGE2 in culture. Authentic PGE2 at concentrations found in CM was found to suppress fibroblast collagen production, indicating that AM-derived PGE2 contributes to the suppressive activity in CM. To examine possible stimulatory factors in CM, the fibroblasts were preincubated with indomethacin. This approach was based on our previous observation that AM-derived suppressive factor increases endogenous fibroblast PGE2 and that its activity can be blocked by indomethacin. Macrophage CM in a concentration of 20% did not suppress the collagen production of indomethacin-treated fibroblasts. However, CM concentrations of 5 and 10% increased collagen production (173 and 143% of control values, respectively), indicating the presence of stimulatory factor(s) in macrophage-conditioned medium

  12. [A study on the activity of nitric oxide in alveolar macrophages from patients with lung cancer].

    Science.gov (United States)

    Hu, C; Li, G; Wu, E

    1998-01-01

    Nitrite and nitrate (NO2-/NO2-) in the bronchus alveolar lavage fluid (BALF) and the supernatants of incubated alveolar macrophages (AMs) from patients with primary lung cancer were measured by copper-coated cadmium reduction and Griess method. Mrna expression of AM induced nitric oxide synthase (iNOS) were analyzed by RT-PCR. There was NO2-/NO2- in BALF either from lung cancer patients or from control subjects. When compared with control group and the nontumor-bearing lung, the level of NO2-/NO2-was lower in BALF from the tumor-bearing lung [5.18+/-1.1 vs 2.47+/-0.67nmol x mg protein-1 (P65+/- 2.46 vs 2.47+/- 0.67nmol x mg protein-1(Pcancer patients than from control and nontumor-bearing lung [95.03+/- 21.76 vs 63.37+/- 17.58nmol (Pcancer patients (69%) and that of control subjects (91%). After the AMs were stimulated with granulocyte-macrophage colony stimulating factor (GM-CSF), the level of NO2-/NO2- in the supernatants was significantly increased (Pcancer resulted in an increase of 16.85+/- 7.58% vs 33.38+/- 8.21% of control group (P< 0.05). These observation suggest that some defects of antitumor function occur in the AMs at the tumor region. GM-CSF can stimulate AMs and thus potentiate their NO activity.

  13. In vivo metabolism of pulmonary alveolar epithelial type II pneumonocytes and macrophages from Syrian hamsters

    International Nuclear Information System (INIS)

    Young adult Syrian hamsters were injected intraperitoneally with 14C-glycerol and 3H-palmitate 17 hr before they were sacrificed and pulmonary alveolar epithelial type II cells and pulmonary alveolar macrophages (PAM) were isolated. Incorporation of the two labeled components into the cellular lipids showed that the 3H-specific activity of the phospholipids from the type II cells was three times that of the PAM and the utilization of 14C-glycerol into phosphatidyl choline (PC) was 50% greater than incorporation into the PC from PAMs. The PC from type II cells showed that 30% was disaturated and from PAMs 21% was disaturated. Another phosphatide, phosphatidyl glycerol contained about one-third of the molecules in disaturated form. These data are consistent with the view that both type II cells and PAMs can synthesize surface-active phospholipids but it is generally accepted that only the pulmonary alveolar epithelial type II cells excrete the disaturated phospholipids which comprise the surface-active components of pulmonary surfactant

  14. Metabolism of (/sup 3/H)benzo(a)pyrene by cultured human bronchus and cultured human pulmonary alveolar macrophages

    DEFF Research Database (Denmark)

    1978-01-01

    (a)pyrene formed by macrophages were 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene (16 to 39%) and two distinct peaks containing unidentified polar metabolites. A negative correction between binding of benzo(a)pyrene to protein and aryl hydrocarbon hydroxylase exists......The metabolism of (/sup 3/H)benzo(a)pyrene by cultured human bronchial epithelium and pulmonary alveolar macrophages was studied. Explants of bronchus were prepared and pulmonary alveolar macrophages were isolated from peripheral lung by trypsinization and by differential adhesion to plastic tissue...... culture dishes. After 7 days in culture the bronchus explant and the macrophages were exposed to (/sup 3/H)benzo(a)pyrene, and the binding to cellular macromolecules was studied. Aryl hydrocarbon hydroxylase activity was determined by the release of tritiated water into the culture medium from metabolized...

  15. Increased iron sequestration in alveolar macrophages in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Quentin Philippot

    Full Text Available Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD pathogenesis. Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer's and Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor, storage (ferritin and export (ferroportin genes was examined by real-time RT-PCR assay. Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1 and the ratio between FEV1 and forced vital capacity (FEV1/FVC. The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Furthermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively. In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative

  16. Expression and regulation of the macrophage inflammatory protein-1 alpha gene by nicotine in rat alveolar macrophages.

    Science.gov (United States)

    Chong, Inn-Wen; Lin, Shiu-Ru; Hwang, Jhi-Jhu; Huang, Ming-Shyan; Wang, Tung-Heng; Hung, Jen-Yu; Paulauskis, Joseph D

    2002-01-01

    Cigarette smoking causes inflammation mainly confined to the airway and lung. Nicotine is one of the primary constituents in cigarette smoke. Alveolar macrophages apparently play a pivotal role in mediating pulmonary inflammation via the production of chemokines. Macrophage inflammatory protein-1 alpha (MIP-1 alpha), a member of CC chemokines, has been shown to contribute to monocyte/macrophage and neutrophil chemotaxis and activation. Our previous work demonstrated that MIP-1 alpha mRNA expression in macrophages is induced by a variety of stimuli. In the present study, we further investigate whether nicotine can regulate the gene expression of MIP-1 alpha in macrophages and determine the mechanism leading to increased expression. A rat alveolar macrophage (RAM) cell line, NR8383, was treated with nicotine at a dose of 3.1, 31, 310 microM, or 3.1 mM. Northern blot analysis showed that the induction of MIP-1 alpha mRNA expression was dose-dependent. To define the time course of the inflammatory response, RAM cells were exposed to 31 microM nicotine, MIP-1 alpha mRNA was induced as early as 1 h after treatment, was maximally expressed at 4 and 6 hours, and reduced by 8 hours. Western blot analysis demonstrated a single band with an estimated molecular weight of 10 kD for MIP-1 alpha which was induced after nicotine treatment, suggesting that expression of MIP-1 alpha mRNA could reflect in protein synthesis. In addition. the increase in MIP-1 alpha mRNA expression induced by nicotine was attenuated by co-treatment with the antioxidant N-acetylcysteine (NAC), at doses of 10 and 20 mM, suggesting that the induction of MIP-1 alpha mRNA is mediated via the generation of reactive oxygen species (ROS). To further investigate transcriptional regulation of the MIP-1 alpha gene expression, RAM cells were exposed to nicotine. MIP-1 alpha mRNA levels were significantly increased in nuclear RNA preparations, indicating that transcriptional activation is involved in increased

  17. Human lung tissue macrophages, but not alveolar macrophages, express matrix metalloproteinases after direct contact with activated T lymphocytes.

    Science.gov (United States)

    Ferrari-Lacraz, S; Nicod, L P; Chicheportiche, R; Welgus, H G; Dayer, J M

    2001-04-01

    Human alveolar macrophages (AM) and lung tissue macrophages (LTM) have a distinct localization in the cellular environment. We studied their response to direct contact with activated T lymphocytes in terms of the production of interstitial collagenase (MMP-1), 92-kD gelatinase (MMP-9), and of TIMP-1, one of the counter-regulatory tissue inhibitors of metalloproteinases. Either AM obtained by bronchoalveolar lavage or LTM obtained by mincing and digestion of lung tissue were exposed for 48 h to plasma membranes of T lymphocytes previously activated with phorbol myristate acetate and phytohemagglutinin for 24 h. Membranes of activated T cells strongly induced the production of MMP-1, MMP-9, and TIMP-1 exclusively in LTM but not in AM, whereas membranes from unstimulated T cells failed to induce the release of MMPs. Both populations of mononuclear phagocytes spontaneously released only small amounts of MMPs and TIMP-1. Similar results were obtained when MMP and TIMP-1 expression was analyzed at pretranslational and biosynthetic levels, respectively. Blockade experiments with cytokine antagonists revealed the involvement of T-cell membrane-associated interleukin-1 and tumor necrosis factor-alpha in MMP production by LTM upon contact with T cells. These data suggest that the ability of lung macrophages to produce MMPs after direct contact with activated T cells is related to the difference in phenotype of mononuclear phagocytes and cell localization. In addition, these observations indicate that cell-cell contact represents an important biological mechanism in potentiating the inflammatory response of mononuclear phagocytes in the lungs. PMID:11306438

  18. Retention of inhaled plutonium oxide. Elimination procedures by pulmonary lavage and effect of the alveolar macrophage

    International Nuclear Information System (INIS)

    A large fraction of the plutonium particles, reaching the deeper lung are retained in the alveolar macrophages during several months. Cell function changes were measured in vivo and in vitro. Stimulation of macrophage mobility and phagocytosis or natural clearance processes were uneffective on PuO2 excretion. In vivo pulmonary lavage was the only effective therapy. The procedures of in toto pulmonary lavage in order to obtain the highest number of macrophages are described. A study of the physiological and histological consequences showed no long-term pathology, lesions observed during 48 h after lavage were restored quickly. A single lavage eliminated 12-25% only of the lung burden. A procedure of ten repeated lavages (1 per week) eliminated 60-90% of the lung burden. The action of lavage seemed twofold: direct elimination in the rinsing liquid and faster pulmonary clearance with low lymph node overload. Survivals in treated animals kept for long-term observations were compatible with the lung burdens remaining after treatment. Demontration of an inhibiting effect on pulmonary fibrosis should indicate a larger utilization

  19. Solubilization of 241AmO2 in alveolar macrophage cultures

    International Nuclear Information System (INIS)

    Cultured rabbit alveolar macrophages were used to study the effect of phagocytosis on the solubilization of 241AmO2. A comparison was made of the solubility of phagocytized AmO2 and AmO2 in cell-free media, in the presence and absence of 0.1 mM DTPA. A time-dependent increase of 26% in the soluble (0.1-μm filtrate) intracellular americium fraction was seen in macrophages cultured for 3 days. The addition of 0.1mM DTPA to culture medium resulted in an increase of 36% over the same time period. In contrast, cell-free media without DTPA resulted in less than a 2% increase in solubility after 4 days of incubation, while addition of 0.1mM DTPA resulted in a 5% increase over the same time period. These results indicate cell-mediated solbuilization of phagocytized AmO2 by macrophages

  20. Patient-derived Granulocyte/Macrophage Colony–Stimulating Factor Autoantibodies Reproduce Pulmonary Alveolar Proteinosis in Nonhuman Primates

    OpenAIRE

    Sakagami, Takuro; Beck, David; Uchida, Kanji; Suzuki, Takuji; Carey, Brenna C.; Nakata, Koh; Keller, Gary; Wood, Robert E.; Wert, Susan E.; Ikegami, Machiko; Whitsett, Jeffrey A.; Luisetti, Maurizio; Davies, Stella; Krischer, Jeffrey P; Brody, Alan

    2010-01-01

    Rationale: Granulocyte/macrophage colony–stimulating factor (GM-CSF) autoantibodies (GMAb) are strongly associated with idiopathic pulmonary alveolar proteinosis (PAP) and are believed to be important in its pathogenesis. However, levels of GMAb do not correlate with disease severity and GMAb are also present at low levels in healthy individuals.

  1. Different particle determinants induce apoptosis and cytokine release in primary alveolar macrophage cultures

    Directory of Open Access Journals (Sweden)

    Schwarze Per E

    2006-06-01

    Full Text Available Abstract Background Particles are known to induce both cytokine release (MIP-2, TNF-α, a reduction in cell viability and an increased apoptosis in alveolar macrophages. To examine whether these responses are triggered by the same particle determinants, alveolar macrophages were exposed in vitro to mineral particles of different physical-chemical properties. Results The crystalline particles of the different stone types mylonite, gabbro, basalt, feldspar, quartz, hornfels and fine grain syenite porphyr (porphyr, with a relatively equal size distribution (≤ 10 μm, but different chemical/mineral composition, all induced low and relatively similar levels of apoptosis. In contrast, mylonite and gabbro induced a marked MIP-2 response compared to the other particles. For particles of smaller size, quartz (≤ 2 μm seemed to induce a somewhat stronger apoptotic response than even smaller quartz (≤ 0.5 μm and larger quartz (≤ 10 μm in relation to surface area, and was more potent than hornfels and porphyr (≤ 2 μm. The reduction in cell viability induced by quartz of the different sizes was roughly similar when adjusted to surface area. With respect to cytokines, the release was more marked after exposure to quartz ≤ 0.5 μm than to quartz ≤ 2 μm and ≤ 10 μm. Furthermore, hornfels (≤ 2 μm was more potent than the corresponding hornfels (≤ 10 μm and quartz (≤ 2 μm to induce cytokine responses. Pre-treatment of hornfels and quartz particles ≤ 2 μm with aluminium lactate, to diminish the surface reactivity, did significantly reduce the MIP-2 response to hornfels. In contrast, the apoptotic responses to the particles were not affected. Conclusion These results indicate that different determinants of mineral/stone particles are critical for inducing cytokine responses, reduction in cell viability and apoptosis in alveolar macrophages. The data suggest that the particle surface reactivity was critical for cytokine responses

  2. Chronic cigarette smoking enhances spontaneous release of tumour necrosis factor-α from alveolar macrophages of rats

    Directory of Open Access Journals (Sweden)

    G. P. Pessina

    1993-01-01

    Full Text Available Some biological effects of chronic cigarette smoking (two cigarettes for 2 h, daily for 4 months in rats were evaluated. During the smoking period, body weight of smoker rats was always significantly lower than that of control rats. Immediately after the last smoking session the carboxyhaemoglobin concentration in the blood was about 8.5% and the polymorphonuclear cells in the bronchoalveolar fluid increased significantly. At the same time, enzymatic analyses on the supernatants of bronchoalveolar fluid revealed a significant increase of β-glucuronidase in the smoker group. Alveolar macrophages, collected 0, 8 and 24 h after the last smoking session, significantly increased the generation of superoxide anion and, after incubation for 24 h at 37° C in a humidified atmosphere, released significantly high amounts of TNF-α. When challenged with lipopolysaccharide, alveolar macrophages of smoker rats released much more TNF-α but, in such a case, TNF-α release was about one half of that observed in the control group. Peritoneal macrophages of both control and smoker rats were unable either to generate high levels of superoxide anion or to release significant amounts of TNF-α. The results clearly demonstrated the activated state of alveolar macrophages and the resting state of peritoneal macrophages.

  3. An Intracellular Arrangement of Histoplasma capsulatum Yeast-Aggregates Generates Nuclear Damage to the Cultured Murine Alveolar Macrophages

    Science.gov (United States)

    Pitangui, Nayla de Souza; Sardi, Janaina de Cássia Orlandi; Voltan, Aline R.; dos Santos, Claudia T.; da Silva, Julhiany de Fátima; da Silva, Rosangela A. M.; Souza, Felipe O.; Soares, Christiane P.; Rodríguez-Arellanes, Gabriela; Taylor, Maria Lucia; Mendes-Giannini, Maria J. S.; Fusco-Almeida, Ana M.

    2016-01-01

    Histoplasma capsulatum is responsible for a human systemic mycosis that primarily affects lung tissue. Macrophages are the major effector cells in humans that respond to the fungus, and the development of respiratory disease depends on the ability of Histoplasma yeast cells to survive and replicate within alveolar macrophages. Therefore, the interaction between macrophages and H. capsulatum is a decisive step in the yeast dissemination into host tissues. Although the role played by components of cell-mediated immunity in the host's defense system and the mechanisms used by the pathogen to evade the host immune response are well understood, knowledge regarding the effects induced by H. capsulatum in host cells at the nuclear level is limited. According to the present findings, H. capsulatum yeast cells display a unique architectural arrangement during the intracellular infection of cultured murine alveolar macrophages, characterized as a formation of aggregates that seem to surround the host cell nucleus, resembling a “crown.” This extranuclear organization of yeast-aggregates generates damage on the nucleus of the host cell, producing DNA fragmentation and inducing apoptosis, even though the yeast cells are not located inside the nucleus and do not trigger changes in nuclear proteins. The current study highlights a singular intracellular arrangement of H. capsulatum yeast near to the nucleus of infected murine alveolar macrophages that may contribute to the yeast's persistence under intracellular conditions, since this fungal pathogen may display different strategies to prevent elimination by the host's phagocytic mechanisms. PMID:26793172

  4. Scanning electron microscopic studies of cultured alveolar macrophages and chrysotile asbestos

    International Nuclear Information System (INIS)

    The physical and chemical characteristics of asbestos and its associated biological toxicity have attracted a good deal of study. While physical factors such as fiber length and surface area may affect the biological response, recent findings suggest that surface charge properties play an important role in asbestos toxocity. To investigate the role of these factors, cultured bovine alveolar macrophages (BAM) were exposed to Canadian chrysotile asbestos samples pretreated by varous means. It was found that heat pretreatment of asbestos reduced cytotoxocity to BAM compared with untreated asbestos. Interestingly, subsequent x-irradiation of heat pretreated asbestos restored cytotoxicity to original (untreated) levels. Scanning electron microscopic evaluations were carried out to determine if pretreatment altered the size distribution of fiber fragments or if BAM interacted with different pretreatments in different ways

  5. A photometric analysis of free alveolar macrophages (FAMs) in smoking and nonsmoking firefighters.

    Science.gov (United States)

    Mehm, W J; Giesecke, G F

    1986-10-01

    The effects of cigarette smoking and chronic smoke inhalation were evaluated in free alveolar macrophages (FAMs) in firefighters and police officers from the city of Denver, CO. Evaluation was accomplished by comparing statistical morphometric and photometric data taken from digital images of FAMs generated by the microscope photometer. Although our results failed to show significant differences between occupations and smoking status in FAM size, degree of size variability, or nuclear/cytoplasmic area ratios, they did demonstrate a significant difference in the degree of nuclear and cytoplasmic optical density (O.D.) between both occupation and smoking status. Firefighters consistently showed significantly greater O.D. values than police officers while smokers demonstrated a significantly greater O.D. than nonsmokers. While the meaning of these findings remains illusive, they do, however, present quantitative data supporting the biological response of the FAM to occupational and cigarette smoke inhalation. PMID:3022703

  6. Studies on the binding and transport processes of americium-241 hydroxide polymers in rat lung and bovine alveolar macrophages

    International Nuclear Information System (INIS)

    The binding of Am-241 hydroxide polymers to the cell components of rat lung was investigated using differential centrifugation, density gradient centrifugation with different media, gel chromatography, free flow electrophoresis and electron microscopic autoradiography with Pu-241. The bovine alveolar macrophage cultures were introduced as an in vitro test system for Am-241 uptake. Form the biochemical and electron microscopic studies it can be concluded that Am-241 is taken up by pulmonary macrophages, where its first storage site is probably the lysosome. Then the Am-241 seems to be solubilized in the lysosomes and to be bound to the cytosolic ferritin of macrophages. Am-241 might be released from the cells and crosses the alveolar membranes as bound to transferrin or as low molecular weight form. (orig.)

  7. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    Science.gov (United States)

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  8. Metabolism of [3H]benzo[a]pyrene by cultured human bronchus and cultured human pulmonary alveolar macrophages

    International Nuclear Information System (INIS)

    The metabolism of [3H]benzo[a]pyrene by cultured human bronchial epithelium and pulmonary alveolar macrophages was studied. Explants of bronchus were prepared and pulmonary alveolar macrophages were isolated from peripheral lung by trypsinization and by differential adhesion to plastic tissue culture dishes. After 7 days in culture the bronchus explant and the macrophages were exposed to [3H]benzo[a]pyrene, and the binding to cellular macromolecules was studied. Aryl hydrocarbon hydroxylase activity was determined by the release of tritiated water into the culture medium from metabolized [3H]benzo[a]pyrene. Variation in the binding level of benzo[a]pyrene to DNA and to protein in macrophages from different individuals showed 9- and 33-fold interindividual variation, respectively. In the macrophages, both binding of benzo[a]pyrene to macromolecules and aryl hydrocarbon hydroxylase activity were dependent on the length of time in culture and length of exposure to benzo[a]pyrene. Pretreatment of the macrophages with benz[α]anthracene increased both binding level of benzo[a]pyrene and aryl hydrocarbon hydroxylase activity. When coincubated with benzo[a]pyrene, cycloheximide, 7,8-benzoflavone, or actinomycin D reduced both level of binding and activity of aryl hydrocarbon hydroxylase. When macrophage cultures were maintained at pO2 greater than atmospheric air, an increase in binding level and enzyme activity was found. The major metabolites of benzo[a]pyrene formed by macrophages were 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, 9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene (16 to 39%) and two distinct peaks containing unidentified polar metabolites. A negative correction between binding of benzo[a]pyrene to protein and aryl hydrocarbon hydroxylase exists in pulmonary macrophages, but no correlation between data from bronchus and macrophages was found

  9. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia.

    Directory of Open Access Journals (Sweden)

    Katrin Högner

    2013-02-01

    Full Text Available Influenza viruses (IV cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using ex vivo and in vivo IV infection models, we demonstrate that alveolar macrophage (AM-expressed IFN-β significantly contributes to IV-induced alveolar epithelial cell (AEC injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL. Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-β release in AM in a protein kinase R- (PKR- and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-β and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-β-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.

  10. Resident alveolar macrophages are susceptible to and permissive of Coxiella burnetii infection.

    Directory of Open Access Journals (Sweden)

    Matthew Calverley

    Full Text Available Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans. Inhalation of low doses of Coxiella bacteria can result in infection of the host alveolar macrophage (AM. However, it is not known whether a subset of AMs within the heterogeneous population of macrophages in the infected lung is particularly susceptible to infection. We have found that lower doses of both phase I and phase II Nine Mile C. burnetii multiply and are less readily cleared from the lungs of mice compared to higher infectious doses. We have additionally identified AM resident within the lung prior to and shortly following infection, opposed to newly recruited monocytes entering the lung during infection, as being most susceptible to infection. These resident cells remain infected up to twelve days after the onset of infection, serving as a permissive niche for the maintenance of bacterial infection. A subset of infected resident AMs undergo a distinguishing phenotypic change during the progression of infection exhibiting an increase in surface integrin CD11b expression and continued expression of the surface integrin CD11c. The low rate of phase I and II Nine Mile C. burnetii growth in murine lungs may be a direct result of the limited size of the susceptible resident AM cell population.

  11. Anti-inflammatory effects of several plant extracts on porcine alveolar macrophages in vitro.

    Science.gov (United States)

    Liu, Y; Song, M; Che, T M; Bravo, D; Pettigrew, J E

    2012-08-01

    Certain plant extracts are bioactive substances of some foods or traditional herbs, known to possess antioxidant, antibacterial, and perhaps immunoregulatory effects. This study investigated the in vitro anti-inflammatory effects of 7 plant extracts (anethol, capsicum oleoresin, carvacrol, cinnamaldehyde, eugenol, garlicon, and turmeric oleoresin) on porcine alveolar macrophages collected from weaned pigs (n = 6 donor pigs) by bronchoalveolar lavage. The experimental design for this assay was a 2 [with or without 1 μg lipopolysaccharide (LPS)/mL] × 5 (5 different amounts of each plant extract) factorial arrangements in a randomized complete block design. The application of plant extracts were 0, 25, 50, 100, and 200 μg/mL, except for cinnamaldehyde and turmeric oleoresin, which were 0, 2.5, 5, 10, and 20 μg/mL. The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to determine the number of live cells, Griess assay was applied to detect nitric oxide (NO) production, and ELISA was used to measure tumor necrosis factor-α (TNF-α), IL-1β, transforming growth factor-β (TGF-β), and IL-10 in the cell culture supernatants of macrophages. The LPS increased (P tested here may have anti-inflammatory effects to varying degrees. PMID:22328722

  12. Trimellitic anhydride-conjugated serum albumin activates rat alveolar macrophages in vitro

    Directory of Open Access Journals (Sweden)

    Bloksma Nanne

    2006-06-01

    Full Text Available Abstract Background Occupational exposure to airborne low molecular weight chemicals, like trimellitic anhydride (TMA, can result in occupational asthma. Alveolar macrophages (AMs are among the first cells to encounter these inhaled compounds and were previously shown to influence TMA-induced asthma-like symptoms in the Brown Norway rat. TMA is a hapten that will bind to endogenous proteins upon entrance of the body. Therefore, in the present study we determined if TMA and TMA conjugated to serum albumin induced the production of the macrophage mediators nitric oxide (NO, tumour necrosis factor (TNF, and interleukin 6 (IL-6 in vitro using the rat AM cell line NR8383 and primary AMs derived from TMA-sensitized and naïve Brown Norway rats. Methods Cells were incubated with different concentrations of TMA, TMA conjugated to bovine serum albumin (BSA, and BSA as a control for 24 h and the culture supernatant was analyzed for mediator content. Results TMA alone was not able to induce the production of mediators by NR8383 cells and primary AMs from sensitized and sham-treated rats. TMA-BSA, on the contrary, dose-dependently stimulated the production of NO, TNF, and IL-6 by NR8383 cells and of NO and TNF, but not IL-6, by primary AMs independent of sensitization. Conclusion Results suggest that although TMA is a highly reactive compound, conjugation to a suitable protein is necessary to induce mediator production by AMs. Furthermore, the observation that effects of TMA-BSA were independent of sensitization suggests involvement of an immunologically non-specific receptor. In the discussion it is argued that a macrophage scavenger receptor is a likely candidate.

  13. Toxicity of Lunar and Martian Dust Simulants to Alveolar Macrophages Isolated from Human Volunteers

    Science.gov (United States)

    Latch, Judith N.; Hamilton, Raymond F., Jr.; Holian, Andrij; James, John T.

    2007-01-01

    NASA is planning to build a habitat on the Moon and use the Moon as a stepping stone to Mars. JSC-1, an Arizona volcanic ash that has mineral properties similar to lunar soil, is used to produce lunar environments for instrument and equipment testing. NASA is concerned about potential health risks to workers exposed to these fine dusts in test facilities. The potential toxicity of JSC-1 and a Martian soil simulant (JSC-Mars-1, a Hawaiian volcanic ash) was evaluated using human alveolar macrophages (HAM) isolated from volunteers; titanium dioxide and quartz were used as reference dusts. This investigation is a prerequisite to studies of actual lunar dust. HAM were treated in vitro with these test dusts for 24 h; assays of cell viability and apoptosis showed that JSC-1 and TiO2 were comparable, and more toxic than saline control, but less toxic than quartz. HAM treated with JSC-1 or JSC-Mars 1 showed a dose-dependent increase in cytotoxicity. To elucidate the mechanism by which these dusts induce apoptosis, we investigated the involvement of the scavenger receptor (SR). Pretreatment of cells with polyinosinic acid, an SR blocker, significantly inhibited both apoptosis and necrosis. These results suggest HAM cytotoxicity may be initiated by interaction of the dust particles with SR. Besides being cytotoxic, silica is known to induce shifting of HAM phenotypes to an immune active status. The immunomodulatory effect of the simulants was investigated. Treatment of HAM with either simulant caused preferential damage to the suppressor macrophage subpopulation, leading to a net increase in the ratio of activator (RFD1+) to suppressor (RFD1+7+) macrophages, a result similar to treatment with silica. It is recommended that appropriate precautions be used to minimize exposure to these fine dusts in large-scale engineering applications.

  14. Lipid-Laden Alveolar Macrophages and pH Monitoring in Gastroesophageal Reflux-Related Respiratory Symptoms

    Directory of Open Access Journals (Sweden)

    R. Kitz

    2012-01-01

    Full Text Available Lipid-laden alveolar macrophages and pH monitoring have been used in the diagnosis of chronic aspiration in children with gastroesophageal reflux (GER. This study was conducted to prove a correlation between the detection of alimentary pulmonary fat phagocytosis and an increasing amount of proximal gastroesophageal reflux. It was assumed that proximal gastroesophageal reflux better correlates with aspiration than distal GER. Patients from 6 months to 16 years with unexplained recurrent wheezy bronchitis and bronchial hyperreactivity, or recurrent pneumonia with chronic cough underwent 24-hour double-channel pH monitoring and bronchoscopy with bronchoalveolar lavage (BAL. Aspiration of gastric content was determined by counting lipid laden alveolar macrophages from BAL specimens. There were no correlations between any pH-monitoring parameters and counts of lipid-laden macrophages in the whole study population, even when restricting analysis to those with abnormal reflux index expressing clinically significant GER. Quantifying lipid-laden alveolar macrophages from BAL in children with gastroesophageal-related respiratory disorders does not have an acceptable specificity to prove chronic aspiration as an underlying etiology. Therefore, research for other markers of pulmonary aspiration is needed.

  15. ROS-mediated TNF-α and MIP-2 gene expression in alveolar macrophages exposed to pine dust

    Directory of Open Access Journals (Sweden)

    Husgafvel-Pursiainen Kirsti

    2004-12-01

    Full Text Available Abstract Background Respiratory symptoms, impaired lung function, and asthma have been reported in workers exposed to wood dust in a number of epidemiological studies. The underlying pathomechanisms, however, are not well understood. Here, we studied the effects of dust from pine (PD and heat-treated pine (HPD on the release of reactive oxygen species (ROS and inflammatory mediators in rat alveolar macrophages. Methods Tumour necrosis factor-alpha (TNF-α and macrophage inflammatory protein-2 (MIP-2 protein release, TNF-α and MIP-2 mRNA expression, and generation of ROS were studied as end points after treatment of rat alveolar macrophages with PD or HPD. In a separate series of experiments, the antioxidants glutathione and N-acetyl-L-cysteine were included in combination with wood dust. To determine the endogenous oxidative and antioxidant capacity of wood dusts, electron spin resonance (ESR spectroscopy was used. Results After 4 h incubation, both PD and HPD elicited a significantly (p Conclusion These results indicate that pine dust is able to induce expression of TNF-α and MIP-2 in rat alveolar macrophages by a mechanism that is, at least in part, mediated by ROS.

  16. Macrophage control of phagocytosed mycobacteria is increased by factors secreted by alveolar epithelial cells through nitric oxide independent mechanisms.

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    Dagbjort H Petursdottir

    Full Text Available Tissue-resident macrophages are heterogeneous with tissue-specific and niche-specific functions. Thus, simplified models of macrophage activation do not explain the extent of heterogeneity seen in vivo. We focus here on the respiratory tract and ask whether factors secreted by alveolar epithelial cells (AEC can influence the functionality of resident pulmonary macrophages (PuM. We have previously reported that factors secreted by AEC increase control of intracellular growth of BCG in macrophages. In the current study, we also aimed to investigate possible mechanisms by which AEC-derived factors increase intracellular control of BCG in both primary murine interstitial macrophages, and bone marrow-derived macrophages and characterize further the effect of these factors on macrophage differentiation. We show that; a in contrast to other macrophage types, IFN-γ did not increase intracellular growth control of Mycobacterium bovis, Bacillus Calmette-Guérin (BCG by interstitial pulmonary macrophages although the same macrophages could be activated by factors secreted by AEC; b the lack of response of pulmonary macrophages to IFN-γ was apparently regulated by suppressor of cytokine signaling (SOCS1; c AEC-derived factors did not induce pro-inflammatory pathways induced by IFN-γ e.g. expression of inducible nitric oxide synthase (iNOS, secretion of nitric oxide (NO, or IL-12, d in contrast to IFN-γ, intracellular bacterial destruction induced by AEC-derived factors was not dependent on iNOS transcription and NO production. Collectively, our data show that PuM were restricted in inflammatory responses mediated by IFN-γ through SOCS1 and that factors secreted by AEC- enhanced the microbicidal capacities of macrophages by iNOS independent mechanisms.

  17. Production of Fibronectin by the Human Alveolar Macrophage: Mechanism for the Recruitment of Fibroblasts to Sites of Tissue Injury in Interstitial Lung Diseases

    Science.gov (United States)

    Rennard, Stephen I.; Hunninghake, Gary W.; Bitterman, Peter B.; Crystal, Ronald G.

    1981-11-01

    Because cells of the mononuclear phagocyte system are known to produce fibronectin and because alveolar macrophages are activated in many interstitial lung diseases, the present study was designed to evaluate a role for the alveolar macrophage as a source of the increased levels of fibronectin found in the lower respiratory tract in interstitial lung diseases and to determine if such fibronectin might contribute to the development of the fibrosis found in these disorders by being a chemoattractant for human lung fibroblasts. Production of fibronectin by human alveolar macrophages obtained by bronchoalveolar lavage and maintained in short-term culture in serum-free conditions was demonstrated; de novo synthesis was confirmed by the incorporation of [14C]proline. This fibronectin had a monomer molecular weight of 220,000 and was antigenically similar to plasma fibronectin. Macrophages from patients with idiopathic pulmonary fibrosis produced fibronectin at a rate 20 times higher than did normal macrophages; macrophages from patients with pulmonary sarcoidosis produced fibronectin at 10 times the normal rate. Macrophages from 6 of 10 patients with various other interstitial disorders produced fibronectin at rates greater than the rate of highest normal control. Human alveolar macrophage fibronectin was chemotactic for human lung fibroblasts, suggesting a functional role for this fibronectin in the derangement of the alveolar structures that is characteristic of these disorders.

  18. Generation and Identification of GM-CSF Derived Alveolar-like Macrophages and Dendritic Cells From Mouse Bone Marrow.

    Science.gov (United States)

    Dong, Yifei; Arif, Arif A; Poon, Grace F T; Hardman, Blair; Dosanjh, Manisha; Johnson, Pauline

    2016-01-01

    Macrophages and dendritic cells (DCs) are innate immune cells found in tissues and lymphoid organs that play a key role in the defense against pathogens. However, they are difficult to isolate in sufficient numbers to study them in detail, therefore, in vitro models have been developed. In vitro cultures of bone marrow-derived macrophages and dendritic cells are well-established and valuable methods for immunological studies. Here, a method for culturing and identifying both DCs and macrophages from a single culture of primary mouse bone marrow cells using the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF) is described. This protocol is based on the established procedure first developed by Lutz et al. in 1999 for bone marrow-derived DCs. The culture is heterogeneous, and MHCII and fluoresceinated hyaluronan (FL-HA) are used to distinguish macrophages from immature and mature DCs. These GM-CSF derived macrophages provide a convenient source of in vitro derived macrophages that closely resemble alveolar macrophages in both phenotype and function. PMID:27404290

  19. Regulation of alveolar macrophage transforming growth factor-beta secretion by corticosteroids in bleomycin-induced pulmonary inflammation in the rat.

    OpenAIRE

    Khalil, N.; Whitman, C.; Zuo, L; Danielpour, D; Greenberg, A

    1993-01-01

    In a model of pulmonary inflammation and fibrosis induced by the antineoplastic antibiotic, bleomycin, we previously demonstrated that TGF-beta was markedly elevated within 7 d of bleomycin administration. At the time of maximal TGF-beta production, TGF-beta 1 was localized by immunohistochemistry to be present almost exclusively in alveolar macrophages. In this study, we have demonstrated that alveolar macrophages stimulated by bleomycin-induced injury secrete large quantities of biologicall...

  20. Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis. A potential mechanism for the recruitment and activation of neutrophils in lung fibrosis.

    OpenAIRE

    Carré, P C; Mortenson, R L; King, T. E.; Noble, P W; Sable, C L; Riches, D W

    1991-01-01

    Neutrophil migration into the airspaces of the lung is thought to contribute to the alveolar damage and subsequent fibrosis in idiopathic pulmonary fibrosis (IPF). Interleukin 8 (IL-8), a monocyte- and macrophage-derived cytokine, displays potent chemotactic and activating properties towards neutrophils and thus may contribute to the pathogenesis of IPF. The objective of this investigation was to quantify the spontaneous expression of IL-8 transcripts by alveolar macrophages from normal healt...

  1. Synergistic effects of bovine respiratory syncytial virus and non-cytopathic bovine viral diarrhea virus infection on selected bovine alveolar macrophage functions.

    OpenAIRE

    Liu, L.; Lehmkuhl, H D; Kaeberle, M L

    1999-01-01

    The effect of bovine respiratory syncytial virus (BRSV) and non-cytopathic bovine viral diarrhea virus (ncpBVDV) infection on selected bovine alveolar macrophage (AM) functions was investigated. Alveolar macrophages were harvested from 2- to 6-month-old calves seronegative for BRSV and BVDV and inoculated with approximately 1 median cell culture infective dose of virus per AM. Control, BRSV infected, ncpBVDV-infected and BRSV-ncpBVDV coinfected AM cultures were evaluated for Fc receptor expre...

  2. Transcription analysis on response of porcine alveolar macrophages to Haemophilus parasuis

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    Wang Yang

    2012-02-01

    Full Text Available Abstract Background Haemophilus parasuis (H. parasuis is the etiological agent of Glässer's disease in pigs. Currently, the molecular basis of this infection is largely unknown. The innate immune response is the first line of defense against the infectious disease. Systematical analysis on host innate immune response to the infection is important for understanding the pathogenesis of the infectious microorganisms. Results A total of 428 differentially expressed (DE genes were identified in the porcine alveolar macrophages (PAMs 6 days after H. parasuis infection. These genes were principally related to inflammatory response, immune response, microtubule polymerization, regulation of transcript and signal transduction. Through the pathway analysis, the significant pathways mainly concerned with cell adhesion molecules, cytokine-cytokine receptor interaction, complement and coagulation cascades, toll-like receptor signaling pathway, MAPK signaling pathway, suggesting that the host took different strategies to activate immune and inflammatory response upon H. parasuis infection. The global interactions network and two subnetworks of the proteins encoded by DE genes were analyzed by using STRING. Further immunostimulation analysis indicated that mRNA levels of S100 calcium-binding protein A4 (S100A4 and S100 calcium-binding protein A6 (S100A6 in porcine PK-15 cells increased within 48 h and were sustained after administration of lipopolysaccharide (LPS and Poly (I:C respectively. The s100a4 and s100a6 genes were found to be up-regulated significantly in lungs, spleen and lymph nodes in H. parasuis infected pigs. We firstly cloned and sequenced the porcine coronin1a gene. Phylogenetic analysis showed that poCORONIN 1A belonged to the group containing the Bos taurus sequence. Structural analysis indicated that the poCORONIN 1A contained putative domains of Trp-Asp (WD repeats signature, Trp-Asp (WD repeats profile and Trp-Asp (WD repeats circular

  3. Eradication of spontaneous metastases and activation of alveolar macrophages by intravenous injection of liposomes containing muramyl dipeptide.

    OpenAIRE

    Fidler, I. J.; Sone, S.; Fogler, W. E.; Barnes, Z L

    1981-01-01

    The multiple systemic administration of multilamellar liposomes composed of phosphatidylserine and phosphatidylcholine (molar ratio 3:7) that contained water-soluble muramyl dipeptide (MDP) activated alveolar macrophages to become tumoricidal and eradicated established spontaneous pulmonary and lymph node metastases. Spontaneously metastasizing melanoma cells were injected into the footpads of mice. After 4-5 weeks, the tumors were resected by a midfemoral amputation; 3 days later, twice-week...

  4. Inhibition of bleomycin-induced pulmonary fibrosis by nordihydroguaiaretic acid. The role of alveolar macrophage activation and mediator production.

    OpenAIRE

    Phan, S. H.; Kunkel, S L

    1986-01-01

    The role of alveolar macrophage activation and release of mediators remains unclear. In this study, this role is examined with respect to the effects of relatively selective inhibitors of arachidonate metabolism on the pathogenesis of pulmonary fibrosis. CBA/J mice were administered bleomycin (0.037 units) endotracheally to induce pulmonary fibrosis. Daily intraperitoneal injections of a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA) inhibited pulmonary fibrosis in a dose-dependent ...

  5. No involvement of alveolar macrophages in the initiation of carbon nanoparticle induced acute lung inflammation in mice

    OpenAIRE

    Chen, Shanze; Yin, Renfu; Mutze, Kathrin; Yu, Youjia; Takenaka, Shinji; Königshoff, Melanie; Stoeger, Tobias

    2016-01-01

    Background Carbonaceous nanoparticles (CNP) represent a major constituent of urban particulate air pollution, and inhalation of high CNP levels has been described to trigger a pro-inflammatory response of the lung. While several studies identified specific particle characteristics driving respiratory toxicity of low-solubility and low-toxicity particles such as CNP, the major lung cell type, which initiates and drives that response, remains still uncertain. Since alveolar macrophages (AM) are...

  6. Reactomes of porcine alveolar macrophages infected with porcine reproductive and respiratory syndrome virus.

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    Zhihua Jiang

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS has devastated pig industries worldwide for many years. It is caused by a small RNA virus (PRRSV, which targets almost exclusively pig monocytes or macrophages. In the present study, five SAGE (serial analysis of gene expression libraries derived from 0 hour mock-infected and 6, 12, 16 and 24 hours PRRSV-infected porcine alveolar macrophages (PAMs produced a total 643,255 sequenced tags with 91,807 unique tags. Differentially expressed (DE tags were then detected using the Bayesian framework followed by gene/mRNA assignment, arbitrary selection and manual annotation, which determined 699 DE genes for reactome analysis. The DAVID, KEGG and REACTOME databases assigned 573 of the DE genes into six biological systems, 60 functional categories and 504 pathways. The six systems are: cellular processes, genetic information processing, environmental information processing, metabolism, organismal systems and human diseases as defined by KEGG with modification. Self-organizing map (SOM analysis further grouped these 699 DE genes into ten clusters, reflecting their expression trends along these five time points. Based on the number one functional category in each system, cell growth and death, transcription processes, signal transductions, energy metabolism, immune system and infectious diseases formed the major reactomes of PAMs responding to PRRSV infection. Our investigation also focused on dominant pathways that had at least 20 DE genes identified, multi-pathway genes that were involved in 10 or more pathways and exclusively-expressed genes that were included in one system. Overall, our present study reported a large set of DE genes, compiled a comprehensive coverage of pathways, and revealed system-based reactomes of PAMs infected with PRRSV. We believe that our reactome data provides new insight into molecular mechanisms involved in host genetic complexity of antiviral activities against PRRSV and

  7. Nrf2 regulates PU.1 expression and activity in the alveolar macrophage.

    Science.gov (United States)

    Staitieh, Bashar S; Fan, Xian; Neveu, Wendy; Guidot, David M

    2015-05-15

    Alveolar macrophage (AM) immune function depends on the activation of the transcription factor PU.1 by granulocyte macrophage colony-stimulating factor. We have determined that chronic alcohol ingestion dampens PU.1 signaling via an unknown zinc-dependent mechanism; specifically, although PU.1 is not known to be a zinc-dependent transcription factor, zinc treatment reversed alcohol-mediated dampening of PU.1 signaling. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a zinc-dependent basic leucine zipper protein essential for antioxidant defenses, is also impaired by chronic alcohol ingestion and enhanced by zinc treatment. We hypothesized that the response of PU.1 to zinc treatment may result from the action of Nrf2 on PU.1. We first performed Nrf2/PU.1 protein coimmunoprecipitation on a rat AM cell line (NR8383) and found no evidence of protein-protein interactions. We then found evidence of increased Nrf2 binding to the PU.1 promoter region by chromatin immunoprecipitation. We next activated Nrf2 using either sulforaphane or an overexpression vector and inhibited Nrf2 with silencing RNA to determine whether Nrf2 could actively regulate PU.1. Nrf2 activation increased protein expression of both factors as well as gene expression of their respective downstream effectors, NAD(P)H dehydrogenase[quinone] 1 (NQO1) and cluster of differentiation antigen-14 (CD14). In contrast, Nrf2 silencing decreased the expression of both proteins, as well as gene expression of their effectors. Activating and inhibiting Nrf2 in primary rat AMs resulted in similar effects. Taken together, these findings suggest that Nrf2 regulates the expression and activity of PU.1 and that antioxidant response and immune activation are coordinately regulated within the AM.

  8. Cytogenetic effects of cigarette smoke on pulmonary alveolar macrophages of the rat

    International Nuclear Information System (INIS)

    This study was part of a larger investigation of the health effects resulting from different methods of exposing rats to cigarette smoke. Cytogenetic effects of cigarette smoke on rat pulmonary alveolar macrophages (PAMs) were evaluated. Fischer 344/N, male rats (4/group) were randomly assigned to 5 different exposure groups: (1) nose-only sham-exposed control, (2) whole-body sham-exposed control, (3) nose-only intermittent, (4) nose-only continuous, and (5) whole-body continuous. Sham controls were exposed to clean air. PAMs were obtained by lung lavage and chromosomal damage was measured. Multiple comparison demonstrated no significant differences between smoke-exposed groups and their respective sham-exposed controls, between the sham-exposed groups, or among the three smoke exposed groups. Highly significant smoke-induced differences in both structural and numerical aberrations were observed when data for the respective control groups and exposed groups were pooled and compared. Results from this study demonstrate the clastogenicity of cigarette smoke on rat PAM. (author)

  9. Uptake characteristics of liposomes by rat alveolar macrophages: influence of particle size and surface mannose modification.

    Science.gov (United States)

    Chono, Sumio; Tanino, Tomoharu; Seki, Toshinobu; Morimoto, Kazuhiro

    2007-01-01

    The influence of particle size and surface mannose modification on the uptake of liposomes by alveolar macrophages (AMs) was investigated in-vitro and in-vivo. Non-modified liposomes of five different particle sizes (100, 200, 400, 1000 and 2000 nm) and mannosylated liposomes with 4-aminophenyl-alpha-D-mannopyranoside (particle size 1000 nm) were prepared, and the uptake characteristics by rat AMs in-vitro and in-vivo were examined. The uptake of non-modified liposomes by rat AMs in-vitro increased with an increase in particle size over the range of 100-1000 nm, and became constant at over 1000 nm. The uptake of non-modified liposomes by AMs after pulmonary administration to rats in-vivo increased with an increase in particle size in the range 100-2000 nm. The uptake of mannosylated liposomes (particle size 1000 nm) by rat AMs both in-vitro and in-vivo was significantly greater than that of non-modified liposomes (particle size 1000 nm). The results indicate that the uptake of liposomes by rat AMs is dependent on particle size and is increased by surface mannose modification.

  10. Subcellular distribution of azithromycin and clarithromycin in rat alveolar macrophages (NR8383) in vitro.

    Science.gov (United States)

    Togami, Kohei; Chono, Sumio; Morimoto, Kazuhiro

    2013-01-01

    Azithromycin (AZM), a 15-membered ring macrolide antimicrobial agent, has an antibacterial spectrum that includes intracellular parasitic pathogens that survive or intracellularly multiply in alveolar macrophages (AMs). The subcellular distribution of AZM in AMs was evaluated in vitro in comparison with clarithromycin (CAM). AZM and CAM (50 µM) were applied to the NR8383 cells, used as an in vitro model of AMs, followed by incubation at 37°C or 4°C. The total amount of AZM in cells and subcellular distribution (cell fractionation) was determined after incubation. High level of AZM accumulation was observed in the NR8383 cells at 37°C, and the equilibrium intracellular to extracellular concentration ratio (I/E ratio) was approximately 680, which was remarkably higher than that of CAM (equilibrium I/E ratio=28). The intracellular accumulation of AZM and CAM was temperature dependent. In addition, AZM distributed to the granules fraction including organelles and soluble fraction including cytosol in the NR8383 cells, whereas CAM mainly distributed in soluble fraction. The amount of AZM in the granules fraction was markedly reduced in the presence of ammonium chloride for increase in intracellular pH. These results indicate that AZM is distributed in acidic compartment in AMs. This study suggests that high AZM accumulation in the NR8383 cells is due to the trapping and/or binding in acidic organelles, such as lysosomes.

  11. Aerosol-based efficient delivery of azithromycin to alveolar macrophages for treatment of respiratory infections.

    Science.gov (United States)

    Togami, Kohei; Chono, Sumio; Morimoto, Kazuhiro

    2013-01-01

    The efficacy of aerosol-based delivery of azithromycin (AZM) for the treatment of respiratory infections caused by pathogenic microorganisms infected in alveolar macrophages (AMs) was evaluated by comparison with oral administration. The aerosol formulation of AZM (0.2 mg/kg) was administered to rat lungs using a Liquid MicroSprayer(®). The oral formulation of AZM (50 mg/kg) was used for comparison. Time-courses of concentrations of AZM in AMs following administration were obtained, and then the therapeutic availability (TA) was calculated. In addition, the area under the concentrations of AZM in AMs - time curve/minimum inhibitory concentration at which 90% of isolates ratio (AUC/MIC90) were calculated to estimate the antibacterial effects in AMs. The TA of AZM in AMs following administration of aerosol formulation was markedly greater than that following administration of oral formulation. In addition, the AUC/MIC90 of AZM in AMs was markedly higher than the effective values. This indicates that the aerosol formulation could be useful for the treatment of respiratory infections caused by pathogenic microorganisms infected in AMs. This study suggests that aerosolized AZM is an effective pulmonary drug delivery system for the treatment of respiratory infections.

  12. Depletion of alveolar macrophages ameliorates virus-induced disease following a pulmonary coronavirus infection.

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    Stacey M Hartwig

    Full Text Available Coronaviruses cause respiratory disease in humans that can range from mild to severe. However, the pathogenesis of pulmonary coronavirus infections is poorly understood. Mouse hepatitis virus type 1 (MHV-1 is a group 2 coronavirus capable of causing severe morbidity and mortality in highly susceptible C3H/HeJ mice. We have previously shown that both CD4 and CD8 T cells play a critical role in mediating MHV-1-induced disease. Here we evaluated the role of alveolar macrophages (AM in modulating the adaptive immune response and subsequent disease. Depletion of AM using clodronate liposomes administered prior to MHV-1 infection was associated with a significant amelioration of MHV-1-induced morbidity and mortality. AM depletion resulted in a decreased number of virus-specific CD4 T cells in the lung airways. In addition, a significant increase in the frequency and total number of Tregs in the lung tissue and lung airways was observed following MHV-1 infection in mice depleted of AM. Our results indicate that AM play a critical role in modulating MHV-1-induced morbidity and mortality.

  13. Viral respiratory infection increases alveolar macrophage cytoplasmic motility in rats: role of NO.

    Science.gov (United States)

    Fukushima, T; Sekizawa, K; Yamaya, M; Okinaga, S; Satoh, M; Sasaki, H

    1995-03-01

    Ingested ferrimagnetic (Fe3O4) particles were used to estimate noninvasively the motion of organelles in alveolar macrophages (AM) in intact rats during viral respiratory infection by parainfluenza type 1 (Sendai) virus. Four days after instillation of Fe3O4 particles (3 mg/kg) into the lung, remnant field strength (RFS) was measured at the body surface immediately after magnetization of Fe3O4 particles by an externally applied magnetic field. RFS decreases with time, due to particle rotation (relaxation) which is related to cytoplasmic motility of AM. Viral infection increased the relaxation rate (lambda o per min), and increases in lambda o reached a maximum 3 days after nasal inoculation (day 3). Viral infection (day 3)-induced increases in lambda o were dose dependently inhibited by either the L-arginine analogue N-nitro-L-arginine or by methylene blue, an inhibitor of guanylate cyclase activity. Bronchoalveolar lavage fluid obtained from infected rats contained significantly higher levels of nitrite than that from control rats (P < 0.01). In in vitro experiments, AM from infected rats showed significantly higher lambda o, nitrite production, and intracellular guanosine 3',5'-cyclic monophosphate levels than those from control rats (P < 0.01). Sodium nitroprusside, known to release nitric oxide concentration dependently, increased lambda o of AM from noninfected rats in vitro. These results suggest that nitric oxide plays an important role in AM cytoplasmic motility during viral respiratory infection. PMID:7900821

  14. Three-dimensional characteristics of alveolar macrophages in vitro observed by dark field microscopy

    Science.gov (United States)

    Swarat, Dominic; Wiemann, Martin; Lipinski, Hans-Gerd

    2014-05-01

    Alveolar macrophages (AM) are cells from immune defense inside the lung. They engulf particles in vacuoles from the outer membrane. Volume and surface are important parameters to characterize the particle uptake. AM change their shape within a few seconds, therefore it is hard to obtain by confocal laser scanning microscopy, which is commonly used to generate 3D-images. So we used an intensified dark field microscopy (DFM) as an alternative method to generate contrast rich AM gray tone image slices used for 3D-reconstructions of AM cells by VTK software applications. From these 3D-reconstructions approximate volume and surface data of the AM were obtained and compared to values found in the literature. Finally, simple geometrical 3D-models of the AM were created and compared to real data. Averaged volume and surface data from the DFM images are close to values found in the literature. Furthermore, calculation of volume and surface data from DFM images could be done faster if simplified geometrical 3D-models of the cells were used.

  15. Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes

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    Rafael L. Simões

    2013-01-01

    Full Text Available Clinical and experimental observations have supported the notion that free heme released during hemorrhagic and hemolytic episodes may have a major role in lung inflammation. With alveolar macrophages (AM being the main line of defense in lung environments, the influence of free heme on AM activity and function was investigated. We observed that heme in a concentration range found during hemolytic episodes (3–30 μM elicits AM to present a proinflammatory profile, stimulating reactive oxygen species (ROS and nitric oxide (NO generation and inducing IL-1β, IL-6, and IL-10 secretion. ROS production is NADPH oxidase-dependent, being inhibited by DPI and apocynin, and involves p47 subunit phosphorylation. Furthermore, heme induces NF-κB nuclear translocation, iNOS, and also HO-1 expression. Moreover, AM stimulated with free heme show enhanced phagocytic and bactericidal activities. Taken together, the data support a dual role for heme in the inflammatory response associated with lung hemorrhage, acting as a proinflammatory molecule that can either act as both an adjuvant of the innate immunity and as an amplifier of the inflammatory response, leading tissue injury. The understanding of heme effects on pulmonary inflammatory processes can lead to the development of new strategies to ameliorate tissue damage associated with hemorrhagic episodes.

  16. Modulation of human alveolar macrophage properties by ozone exposure in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Becker, S.; Madden, M.C.; Newman, S.L.; Devlin, R.B.; Koren, H.S.

    1991-01-01

    The study investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3)(0.1-1.0 ppm for 2-4 hr). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2(PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, the authors found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2) production in response to phorbol ester was reduced after exposure of HAM to O3 while the basal O2 release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3-exposed HAM produced significantly lower levels of these cytokines when simulated with bacterial lipopolysaccharide (LPS).

  17. Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection.

    Directory of Open Access Journals (Sweden)

    Christoph Schneider

    2014-04-01

    Full Text Available Alveolar macrophages (AM are critical for defense against bacterial and fungal infections. However, a definitive role of AM in viral infections remains unclear. We here report that AM play a key role in survival to influenza and vaccinia virus infection by maintaining lung function and thereby protecting from asphyxiation. Absence of AM in GM-CSF-deficient (Csf2-/- mice or selective AM depletion in wild-type mice resulted in impaired gas exchange and fatal hypoxia associated with severe morbidity to influenza virus infection, while viral clearance was affected moderately. Virus-induced morbidity was far more severe in Csf2-/- mice lacking AM, as compared to Batf3-deficient mice lacking CD8α+ and CD103+ DCs. Csf2-/- mice showed intact anti-viral CD8+ T cell responses despite slightly impaired CD103+ DC development. Importantly, selective reconstitution of AM development in Csf2rb-/- mice by neonatal transfer of wild-type AM progenitors prevented severe morbidity and mortality, demonstrating that absence of AM alone is responsible for disease severity in mice lacking GM-CSF or its receptor. In addition, CD11c-Cre/Ppargfl/fl mice with a defect in AM but normal adaptive immunity showed increased morbidity and lung failure to influenza virus. Taken together, our results suggest a superior role of AM compared to CD103+ DCs in protection from acute influenza and vaccinia virus infection-induced morbidity and mortality.

  18. An In Vitro Investigation of Pulmonary Alveolar Macrophage Cytotoxicity Introduced by Fibrous and Grainy Mineral Dusts

    Institute of Scientific and Technical Information of China (English)

    DONG Faqin; DENG Jianjun; WU Fengchun; PU Xiaoyong; John HUANG; FENG Qiming; HE Xiaochun

    2006-01-01

    In order to study the damage mechanism of mineral dusts on the pulmonary alveolar macrophage (AM), the changes in their death ratio, malandialdthyde (MDA) content and activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) were measured, and the technique of cell culture in vitro was used to investigate the cytotoxicity of six mineral dusts (twelve crystal habits)from twelve mineral deposits. The results show that wollastonite and clinoptilolite have no AM cytotoxicity, while other fibrous and grainy mineral dusts damage pulmonary AM in various degrees.The cytotoxicity of fibrous mineral dusts was greater than that of the grainy ones, and the cytotoxicity of dusts was positively correlated with the active OH- content in dusts, but not necessarily so with its SiO2 content. The high pH values produced by dust was unfavorable for the survival of cells and the dusts with low bio-resistance were safe for cells. The content of variable valence elements in dusts might influence their cytotoxicity and the surface charge of dusts was not a stable factor for their toxicity. It is demonstrated that the shape of mineral dusts was one of the factors affecting cytotoxicity, and that the cytotoxicity of mineral dusts depends mainly on their properties.

  19. Effects of ozone exposure on lipid metabolism in human alveolar macrophages

    International Nuclear Information System (INIS)

    Alveolar macrophages (AM) store arachidonic acid (AA) which is esterified in cellular phospholipids until liberated by phospholipase A2 or C after exposure to inflammatory stimuli. Following release, there can be subsequent metabolism of AA into various potent, biological active mediators including prostaglandins and platelet activating factor (PAF). To examine the possibility that these mediators may account for some of the pathophysiologic alterations seen in the lung following O3 exposure, human AM were collected by bronchoalveolar lavage of normal subjects, plated into tissue culture dishes, and the adherent cells were incubated with 3H-AA or 3H-lysoPAF. Human AM exposed 1.0 ppm O3 for 2 hr released 65 + or - 12% more tritium, derived from 3H-AA, than paired air-exposed controls into media supernatants. In other studies using a similar O3 exposure protocol, there was also a significant increase in human AM PGE2 production (2.0 + or - 0.5 fold-increase above air-exposure values, p<0.01, n=17). In additional studies, using a similar O3 exposure protocol (1.0 ppm for 1 hr), there was also a significant increase in human AM PAF content (1.7 + or - 0.2 fold-increase above air-exposure values, p<0.02, n=5)

  20. Composition of coal dusts and their cytotoxicity on alveolar macrophages. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C.Y.; Lee, S.L.; Sheehan, C.E.; Wang, Y.

    1996-09-01

    Coal mine dust is produced from complex materials consisting of organic sedimentary strata, inorganic minerals, and trace elements. The dust varies in its chemical compositions and is capable of causing lung injury and damage when inhaled. The purpose of this study was to perform scanning electron microscopy combined with energy-dispersive spectrometry, wavelength-dispersive spectrometry, and X-ray diffraction analyses of three coal dusts, and examine their effects on rat lung alveolar macrophages (AMs) in cell culture. The coal dusts were obtained from coal surfaces of anthracite, meager, and fat coal mines. The AMs were harvested in bronchoalveolar lavage from adult male Wistar rats and were cultured in Eagle`s medium at 37 deg C. Prostaglandin E2 (PGE2) and lactate dehydrogenase (LD) released by cultured AMs were measured by radioimmunoassay and enzymatic methods, respectively, 24 hours after addition of coal dust. Cytotoxicity was evident in AM culture of all three coal dusts, which caused the release of LD and PGE2. The release was dose-dependent. In summary, our study shows that all three coal dusts exhibit cytotoxicity to AMs and suggests that the pathogenesis of coal associated with pulmonary disease may be linked to the elemental compositions and mineralogic components.

  1. Elemental analysis of lung tissue particles and intracellular iron content of alveolar macrophages in pulmonary alveolar proteinosis

    OpenAIRE

    Ohkubo Takeru; Yokoyama Akihito; Koka Masashi; Satoh Takahiro; Yanagitani Noriko; Dobashi Kunio; Matsuzaki Shinichi; Shimizu Yasuo; Ishii Yasuyuki; Kamiya Tomihiro; Mori Masatomo

    2011-01-01

    Abstract Background Pulmonary alveolar proteinosis (PAP) is a rare disease occurred by idiopathic (autoimmune) or secondary to particle inhalation. The in-air microparticle induced X-ray emission (in-air micro-PIXE) system performs elemental analysis of materials by irradiation with a proton microbeam, and allows visualization of the spatial distribution and quantitation of various elements with very low background noise. The aim of this study was to assess the secondary PAP due to inhalation...

  2. Burkholderia mallei and Burkholderia pseudomallei stimulate differential inflammatory responses from human alveolar type II cells (ATII and macrophages.

    Directory of Open Access Journals (Sweden)

    Richard eLu

    2012-12-01

    Full Text Available Alveolar type II pneumocytes (ATII and alveolar macrophages (AM play a crucial role in the lung’s innate immune response. Burkholderia pseudomallei (BP and Burkholderia mallei (BM are facultative Gram-negative bacilli that cause melioidosis and glanders, respectively. The inhalation of these pathogens can cause lethal disease and death in humans. We sought to compare the pathogenesis of and host responses to BP and BM through contact with human primary ATII cells and monocytes-derived macrophages (MDM. We hypothesized that because BP and BM induce different disease outcomes, each pathogen would induce distinct, unique host immune responses from resident pulmonary cells. Our findings showed that BP adhered readily to ATII cells compared to BM. BP, but not BM, was rapidly internalized by macrophages where it replicated to high numbers. Further, BP induced significantly higher levels of pro-inflammatory cytokine secretion from ATII cells (IL-6, IL-8 and macrophages (IL-6, TNFα at 6h post-infection compared to BM (p<0.05. Interestingly, BM induced the anti-inflammatory cytokine, IL-10, in ATII cells and macrophages at 6h post-infection, with delayed induction of inflammatory cytokines at 24h post-infection. Because BP is flagellated and produces LPS, we confirmed that it stimulated both Toll-like receptor (TLR 4 and TLR5 via NF-κb activation while the non-flagellated BM stimulated only TLR4. These data show the differences in BP and BM pathogenicity in the lung when infecting human ATII cells and macrophages and demonstrate the ability of these pathogens to elicit distinct immune responses from resident lung cells which may open new targets for therapeutic intervention to fight against these pathogens.

  3. No evidence of altered alveolar macrophage polarization, but reduced expression of TLR2, in bronchoalveolar lavage cells in sarcoidosis

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    Wikén Maria

    2010-09-01

    Full Text Available Abstract Background Sarcoidosis is a granulomatous inflammatory disease, possibly of infectious aetiology. We aimed to investigate whether the degree of functional polarization of alveolar macrophages (AMs, or Toll-like receptor (TLR expression, is associated with sarcoidosis or with distinct clinical manifestations of this disease. Methods Total BAL cells (cultured four or 24 h in medium, or stimulated 24 h with LPS from 14 patients and six healthy subjects, sorted AMs from 22 patients (Löfgren's syndrome n = 11 and 11 healthy subjects, and sorted CD4+ T cells from 26 patients (Löfgren's syndrome n = 13 and seven healthy subjects, were included. Using real-time PCR, the relative gene expression of IL-10, IL-12p35, IL-12p40, IL-23p19, CCR2, CCR7, iNOS, CXCL10, CXCL11, CXCL16, CCL18, CCL20, CD80, and CD86, and innate immune receptors TLR2, TLR4, and TLR9, was quantified in sorted AMs, and for selected genes in total BAL cells, while IL-17A was quantified in T cells. Results We did not find evidence of a difference with regard to alveolar macrophage M1/M2 polarization between sarcoidosis patients and healthy controls. TLR2 gene expression was significantly lower in sorted AMs from patients, particular in Löfgren's patients. CCL18 gene expression in AMs was significantly higher in patients compared to controls. Additionally, the IL-17A expression was lower in Löfgren's patients' CD4+ T cells. Conclusions Overall, there was no evidence for alveolar macrophage polarization in sarcoidosis. However, there was a reduced TLR2 mRNA expression in patients with Löfgren's syndrome, which may be of relevance for macrophage interactions with a postulated sarcoidosis pathogen, and for the characteristics of the ensuing T cell response.

  4. Alveolar macrophages infected with Ames or Sterne strain of Bacillus anthracis elicit differential molecular expression patterns.

    Directory of Open Access Journals (Sweden)

    Felicia D Langel

    Full Text Available Alveolar macrophages (AMs phagocytose Bacillus anthracis following inhalation and induce the production of pro-inflammatory cytokines and chemokines to mediate the activation of innate immunity. Ames, the virulent strain of B. anthracis, contains two plasmids that encode the antiphagocytic poly-γ-d-glutamic acid capsule and the lethal toxin. The attenuated Sterne strain of B. anthracis, which lacks the plasmid encoding capsule, is widely adapted as a vaccine strain. Although differences in the outcome of infection with the two strains may have originated from the presence or absence of an anti-phagocytic capsule, the disease pathogenesis following infection will be manifested via the host responses, which is not well understood. To gain understanding of the host responses at cellular level, a microarray analysis was performed using primary rhesus macaque AMs infected with either Ames or Sterne spores. Notably, 528 human orthologs were identified to be differentially expressed in AMs infected with either strain of the B. anthracis. Meta-analyses revealed genes differentially expressed in response to B. anthracis infection were also induced upon infections with multiple pathogens such as Francisella Novicida or Staphylococcus aureus. This suggests the existence of a common molecular signature in response to pathogen infections. Importantly, the microarray and protein expression data for certain cytokines, chemokines and host factors provide further insights on how cellular processes such as innate immune sensing pathways, anti-apoptosis versus apoptosis may be differentially modulated in response to the virulent or vaccine strain of B. anthracis. The reported differences may account for the marked difference in pathogenicity between these two strains.

  5. The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter

    International Nuclear Information System (INIS)

    Emerging epidemiological evidence suggests that exposure to particulate matter (PM) air pollution increases the risk of cardiovascular events but the exact mechanism by which PM has adverse effects is still unclear. Alveolar macrophages (AM) play a major role in clearing and processing inhaled PM. This comprehensive review of research findings on immunological interactions between AM and PM provides potential pathophysiological pathways that interconnect PM exposure with adverse cardiovascular effects. Coarse particles (10 μm or less, PM10) induce innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while fine (2.5 μm or less, PM2.5) and ultrafine particles (0.1 μm or less, UFP) induce via reactive oxygen species generation by transition metals and/or polyaromatic hydrocarbons. The innate immune responses are characterized by activation of transcription factors [nuclear factor (NF)-κB and activator protein-1] and the downstream proinflammatory cytokine [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α] production. In addition to the conventional opsonin-dependent phagocytosis by AM, PM can also be endocytosed by an opsonin-independent pathway via scavenger receptors. Activation of scavenger receptors negatively regulates the TLR4-NF-κB pathway. Internalized particles are subsequently subjected to adaptive immunity involving major histocompatibility complex class II (MHC II) expression, recruitment of costimulatory molecules, and the modulation of the T helper (Th) responses. AM show atypical antigen presenting cell maturation in which phagocytic activity decreases while both MHC II and costimulatory molecules remain unaltered. PM drives AM towards a Th1 profile but secondary responses in a Th1- or Th-2 up-regulated milieu drive the response in favor of a Th2 profile.

  6. The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Ryohei; Eeden, Stephan F. van, E-mail: Stephan.vanEeden@hli.ubc.ca

    2011-12-15

    Emerging epidemiological evidence suggests that exposure to particulate matter (PM) air pollution increases the risk of cardiovascular events but the exact mechanism by which PM has adverse effects is still unclear. Alveolar macrophages (AM) play a major role in clearing and processing inhaled PM. This comprehensive review of research findings on immunological interactions between AM and PM provides potential pathophysiological pathways that interconnect PM exposure with adverse cardiovascular effects. Coarse particles (10 {mu}m or less, PM{sub 10}) induce innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while fine (2.5 {mu}m or less, PM{sub 2.5}) and ultrafine particles (0.1 {mu}m or less, UFP) induce via reactive oxygen species generation by transition metals and/or polyaromatic hydrocarbons. The innate immune responses are characterized by activation of transcription factors [nuclear factor (NF)-{kappa}B and activator protein-1] and the downstream proinflammatory cytokine [interleukin (IL)-1{beta}, IL-6, and tumor necrosis factor-{alpha}] production. In addition to the conventional opsonin-dependent phagocytosis by AM, PM can also be endocytosed by an opsonin-independent pathway via scavenger receptors. Activation of scavenger receptors negatively regulates the TLR4-NF-{kappa}B pathway. Internalized particles are subsequently subjected to adaptive immunity involving major histocompatibility complex class II (MHC II) expression, recruitment of costimulatory molecules, and the modulation of the T helper (Th) responses. AM show atypical antigen presenting cell maturation in which phagocytic activity decreases while both MHC II and costimulatory molecules remain unaltered. PM drives AM towards a Th1 profile but secondary responses in a Th1- or Th-2 up-regulated milieu drive the response in favor of a Th2 profile.

  7. Glucocorticoid-Augmented Efferocytosis Inhibits Pulmonary Pneumococcal Clearance in Mice by Reducing Alveolar Macrophage Bactericidal Function.

    Science.gov (United States)

    Stolberg, Valerie R; McCubbrey, Alexandra L; Freeman, Christine M; Brown, Jeanette P; Crudgington, Sean W; Taitano, Sophina H; Saxton, Bridget L; Mancuso, Peter; Curtis, Jeffrey L

    2015-07-01

    Inhaled corticosteroids (ICS) increase community-acquired pneumonia (CAP) incidence in patients with chronic obstructive pulmonary disease (COPD) by unknown mechanisms. Apoptosis is increased in the lungs of COPD patients. Uptake of apoptotic cells (ACs) ("efferocytosis") by alveolar macrophages (AMøs) reduces their ability to combat microbes, including Streptococcus pneumoniae, the most common cause of CAP in COPD patients. Having shown that ICS significantly increase AMø efferocytosis, we hypothesized that this process, termed glucocorticoid-augmented efferocytosis, might explain the association of CAP with ICS therapy in COPD. To test this hypothesis, we studied the effects of fluticasone, AC, or both on AMøs of C57BL/6 mice in vitro and in an established model of pneumococcal pneumonia. Fluticasone plus AC significantly reduced TLR4-stimulated AMø IL-12 production, relative to either treatment alone, and decreased TNF-α, CCL3, CCL5, and keratinocyte-derived chemoattractant/CXCL1, relative to AC. Mice treated with fluticasone plus AC before infection with viable pneumococci developed significantly more lung CFUs at 48 h. However, none of the pretreatments altered inflammatory cell recruitment to the lungs at 48 h postinfection, and fluticasone plus AC less markedly reduced in vitro mediator production to heat-killed pneumococci. Fluticasone plus AC significantly reduced in vitro AMø killing of pneumococci, relative to other conditions, in part by delaying phagolysosome acidification without affecting production of reactive oxygen or nitrogen species. These results support glucocorticoid-augmented efferocytosis as a potential explanation for the epidemiological association of ICS therapy of COPD patients with increased risk for CAP, and establish murine experimental models to dissect underlying molecular mechanisms. PMID:25987742

  8. Modulation of human alveolar macrophage properties by ozone exposure in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Becker, S.; Madden, M.C.; Newman, S.L.; Devlin, R.B.; Koren, H.S. (ABB Environmental Services, Inc., Chapel Hill, NC (United States))

    1991-09-15

    The authors have investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2 (PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, we found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2-) production in response to phorbol ester was reduced after exposure of HAM to O3 while the basal O2- release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3- exposed HAM produced significantly lower levels of these cytokines when stimulated with bacterial lipopolysaccharide (LPS). Two-dimensional gel electrophoretic analysis of proteins made by HAM following in vitro exposure to O3 identified 11 proteins whose rate of synthesis was significantly altered. Thus, these studies show that exposure to O3 alters the functional competence of HAM. While there is a minimal effect on protein expression or synthesis, the responses of HAM to particulate immune complexes, to bacterial LPS, and to PMA are impaired. The release of arachidonic acid and PGE2 suggest that the effect of O3 is primarily targeted to the HAM cell membrane. These changes may ultimately result in increased susceptibility to inhaled infectious agents in the O3-exposed individual.

  9. The FGL2/fibroleukin prothrombinase is involved in alveolar macrophage activation in COPD through the MAPK pathway

    International Nuclear Information System (INIS)

    Fibrinogen-like protein 2 (FGL2)/fibroleukin has been reported to play a vital role in the pathogenesis of some critical inflammatory diseases by possessing immunomodulatory activity through the mediation of 'immune coagulation' and the regulation of maturation and proliferation of immune cells. We observed upregulated FGL2 expression in alveolar macrophages from peripheral lungs of chronic obstructive pulmonary disease (COPD) patients and found a correlation between FGL2 expression and increased macrophage activation markers (CD11b and CD14). The role of FGL2 in the activation of macrophages was confirmed by the detection of significantly decreased macrophage activation marker (CD11b, CD11c, and CD71) expression as well as the inhibition of cell migration and inflammatory cytokine (IL-8 and MMP-9) production in an LPS-induced FGL2 knockdown human monocytic leukemia cell line (THP-1). Increased FGL2 expression co-localized with upregulated phosphorylated p38 mitogen-activated protein kinase (p38-MAPK) in the lung tissues from COPD patients. Moreover, FGL2 knockdown in THP-1 cells significantly downregulated LPS-induced phosphorylation of p38-MAPK while upregulating phosphorylation of c-Jun N-terminal kinase (JNK). Thus, we demonstrate that FGL2 plays an important role in macrophage activation in the lungs of COPD patients through MAPK pathway modulation.

  10. Fibrinogen enhances the inflammatory response of alveolar macrophages to TiO2, SiO2 and carbon nanomaterials.

    Science.gov (United States)

    Marucco, Arianna; Gazzano, Elena; Ghigo, Dario; Enrico, Emanuele; Fenoglio, Ivana

    2016-01-01

    Many studies have shown that the composition of the protein corona dramatically affects the response of cells to nanomaterials (NMs). However, the role of each single protein is still largely unknown. Fibrinogen (FG), one of the most abundant plasma proteins, is believed to mediate foreign-body reactions. Since this protein is absent in cell media used in in vitro toxicological tests the possible FG-mediated effects have not yet been assessed. Here, the effect of FG on the toxicity of three different kinds of inorganic NMs (carbon, SiO2 and TiO2) on alveolar macrophages has been investigated. A set of integrated techniques (UV-vis spectroscopy, dynamic light scattering and sodium dodecyl sulphate-polyacrylamide gel electrophoresis) have been used to study the strength and the kinetics of interaction of FG with the NMs. The inflammatory response of alveolar macrophages (MH-S) exposed to the three NMs associated with FG has also been investigated. We found that FG significantly enhances the cytotoxicity (lactate dehydrogenase leakage) and the inflammatory response (increase in nitric oxide (NO) concentration and NO synthase activation) induced by SiO2, carbon and TiO2 NMs on alveolar macrophages. This effect appears related to the amount of FG interacting with the NMs. In the case of carbon NMs, the activation of fibrinolysis, likely related to the exposure of cryptic sites of FG, was also observed after 24 h. These findings underline the critical role played by FG in the toxic response to NMs.

  11. Adenovirus Vectors Block Human Immunodeficiency Virus–1 Replication in Human Alveolar Macrophages by Inhibition of the Long Terminal Repeat

    OpenAIRE

    Kaner, Robert J.; Santiago, Francisco; Rahaghi, Franck; Michaels, Elizabeth; Moore, John P.; Crystal, Ronald G.

    2009-01-01

    Heterologous viruses may transactivate or suppress human immunodeficiency virus (HIV)–1 replication. An adenovirus type 5 gene transfer vector (Ad5) HIV-1 vaccine was recently evaluated in a clinical trial, without efficacy. In this context, it is relevant to ask what effect Ad vectors have on HIV-1 replication, particularly in cells that are part of the innate immune system. Infection of HIV-1–infected human alveolar macrophages (AMs) obtained from HIV-1+ individuals with an Ad vector contai...

  12. The exhibition to ozone diminishes the adherence and increases the membrane permeability of macrophages alveolar of rate

    International Nuclear Information System (INIS)

    Ozone gas is generated photochemically in areas with high levels of automotive or industrial emissions, and causes irritation and inflammation of the airways if inhaled. Rat alveolar macrophages were obtained by lung lavage from male Sprague Dawley rats and used as a model to assess ozone induced cell damage (0,594 ppm for up to 60 minutes). Ozone exposure caused loss of cell adherence to a polystyrene substrate and increased membrane permeability, as noted by increases in specific 51Cr release and citoplasmic calcium levels. The results indicate that the cell membrane is a target for ozone damage. Elevations of cytoplasmic calcium could mediate other macrophage responses to ozone , including eicosanoid and nitric oxide production, with concomitant decreases in phagocytic ability and superoxide production. (Author)

  13. CX3CL1(+ Microparticles Mediate the Chemoattraction of Alveolar Macrophages toward Apoptotic Acute Promyelocytic Leukemic Cells

    Directory of Open Access Journals (Sweden)

    Wen-Hui Tsai

    2014-02-01

    Full Text Available Background/Aims: During the resolution phase of inflammation, release of “find-me” signals by apoptotic cells is crucial in the chemoattraction of macrophages toward apoptotic cells for subsequent phagocytosis, in which microparticles derived from apoptotic cells (apo-MPs are involved. A recent study reports that CX3CL1 is released from apoptotic cells to stimulate macrophages chemotaxis. In this study, we investigated the role of CX3CL1 in the apo-MPs in the cell-cell interaction between alveolar macrophage NR8383 cells and apoptotic all-trans retinoic acid-treated NB4 (ATRA-NB4 cells. Methods/Results: Apoptotic ATRA-NB4 cells and their conditioning medium (CM enhanced the chemoattraction of NR8383 cells as well as their phagocytosis activity in engulfing apoptotic ATRA-NB4 cells. The levels of CX3CL1(+ apo-MPs and CX3CL1 were rapidly elevated in the CM of ATRA-NB4 cell culture after induction of apoptosis. Both exogenous CX3CL1 and apo-MPs enhanced the transmigration of NR8383 cells toward apoptotic ATRA-NB4 cells. This pro-transmigratory activity was able to be partially inhibited either by blocking the CX3CR1 (CX3CL1 receptor of NR8383 cells with its specific antibody or by blocking the surface CX3CL1 of apo-MPs with its specific antibody before incubating these apo-MPs with NR8383 cells. Conclusion: CX3CL1(+ apo-MPs released by apoptotic cells mediate the chemotactic transmigration of alveolar macrophages.

  14. Neutrophil and Alveolar Macrophage-Mediated Innate Immune Control of Legionella pneumophila Lung Infection via TNF and ROS.

    Science.gov (United States)

    Ziltener, Pascal; Reinheckel, Thomas; Oxenius, Annette

    2016-04-01

    Legionella pneumophila is a facultative intracellular bacterium that lives in aquatic environments where it parasitizes amoeba. However, upon inhalation of contaminated aerosols it can infect and replicate in human alveolar macrophages, which can result in Legionnaires' disease, a severe form of pneumonia. Upon experimental airway infection of mice, L. pneumophila is rapidly controlled by innate immune mechanisms. Here we identified, on a cell-type specific level, the key innate effector functions responsible for rapid control of infection. In addition to the well-characterized NLRC4-NAIP5 flagellin recognition pathway, tumor necrosis factor (TNF) and reactive oxygen species (ROS) are also essential for effective innate immune control of L. pneumophila. While ROS are essential for the bactericidal activity of neutrophils, alveolar macrophages (AM) rely on neutrophil and monocyte-derived TNF signaling via TNFR1 to restrict bacterial replication. This TNF-mediated antibacterial mechanism depends on the acidification of lysosomes and their fusion with L. pneumophila containing vacuoles (LCVs), as well as caspases with a minor contribution from cysteine-type cathepsins or calpains, and is independent of NLRC4, caspase-1, caspase-11 and NOX2. This study highlights the differential utilization of innate effector pathways to curtail intracellular bacterial replication in specific host cells upon L. pneumophila airway infection. PMID:27105352

  15. The induction of nuclear abnormalities in the alveolar macrophages of mouse lung after inhalation of 239PuO2

    International Nuclear Information System (INIS)

    Effects of inhaled 239PuO2 on the free-cell population of the lungs of CBA/H mice have been studied using broncho-alveolar lavage following initial alveolar depositions (IADs) of 209 to 2800 Bq. The numbers of pulmonary alveolar macrophages (PAM) were quantified using a radioactive tracer technique. The number of PAM declined soon after exposure; the extent of the depression and the time taken to reach the nadir were both dose-dependent. Numbers eventually returned to normal but, with high IADs, only after 3 months. The number of binucleate PAM and those with micronuclei increased following relatively low IADs in a dose-dependent manner. Micronucleate PAM were the most sensitive indicator of cellular damage as a result of 239PuO2 inhalation, providing a short-term assessment of radiation damage to lung cells at doses known to produce lung tumors. The results also provide further evidence that mitosis in PAM, or in their precursor cells, does occur within the lung. (author)

  16. Application of the alkaline comet assay to rat alveolar macrophages after homogeneous or heterogeneous irradiation: a biological dosimetry method

    International Nuclear Information System (INIS)

    The alkaline comet assay, also called alkaline single cell gel electrophoresis, is a simple technique to assess single strand breaks, double strand breaks and alkali sites. It is based on the ability of broken DNA to migrate more easily in an electric field than normal DNA. This method is well adapted for the assessment of the ionising radiations effects on single cells. The aim of this study is to develop a biological dosimetry method to estimate the dose delivered to the respiratory tract by an homogeneous (60Co) or an heterogeneous (radon) irradiation. The animal model chosen is the rat because it has been validated for the study of the carcinogenic role of radon in man. Alveolar macrophages have been selected for there homogeneous distribution in the deep lung. After an in vivo thoracic 60Co gamma irradiation or a radon inhalation, it can be considered that these cells received a dose which is representative from the whole dose received by the lung. The comet assay is performed on alveolar macrophages recovered by broncho-alveolar lavage, and comet moment is measured with an epi-fluorescence microscope coupled to an image acquisition and analysis computing system. The results show the residence of a dose - comet moment relationship after in vivo 60Co gamma and radon irradiations. The technique used enabled us to show differences between homogeneous and heterogeneous irradiations in term of comet moments distributions. Although these results are promising, this technique has to be improved for the detection of biological effects induced by low doses of irradiation in order to detect potential effects of indoor radon exposure. (authors)

  17. Involvement of protein kinase C, phospholipase C, and protein tyrosine kinase pathways in oxygen radical generation by asbestos-stimulated alveolar macrophage.

    OpenAIRE

    Lim, Y.; Kim, S. H.; Kim, K A; Oh, M W; Lee, K. H.

    1997-01-01

    Although asbestos stimulates oxygen radical generation in alveolar macrophages, the exact mechanism is still not clear. The purpose of this study was to compare the ability of three asbestos fibers (amosite, chrysotile, and crocidolite) to generate oxygen radicals in macrophages and examine the mechanism of this action. All asbestos fibers were able to induce chemiluminescence but chrysotile induced maximal chemiluminescence at higher concentrations than amosite and crocidolite. Protein kinas...

  18. Electron microscope study on the relationship between macrophages of the alevolar space and spheroid alveolar epithelial cells on mice after injection of squid-ink (sepia-melanin solution into the trachea

    Directory of Open Access Journals (Sweden)

    Suwa,Kiichi

    1977-02-01

    Full Text Available The relationship between alveolar macrophages and spheroid alveolar epithelial cells was studied with the electron microscope after injection of squid-ink solution into the trachea of the mouse. At 20 hours after injection of squid-ink solution slight degeneration was evident in alveolar macrophages with sepia-melanin particles being phagocytized with partial digestion by lysosmes. Furthermore, hardly any changes were seen in mitochondria and inclusion bodies of the spheroid alveolar epithelial cells. In contrast, at one week after injection of squid-ink solution, almost all alveolar macrophages were degenerated with destruction of the ectoplasm in which the ingested sepia-melanin particles were digested by lysosomes into fine particles, and the mitochondria of spheroid alveolar epithelial cells were degenerated and the inclusion bodies were hardly formed. At three weeks after injection of squid-ink solution, alveolar macrophages as well as speroid alveolar epithelial cells showed almost complete recovery of functional structure. As the phagocyte in the alveolar space, neutrophile leucocytes were also observed in addition to the so-called alveolar macrophage.

  19. Pulmonary alveolar proteinosis

    OpenAIRE

    Crestani, B; Epaud, R.; Aubier, M.; M-C. Dombret; Taille, C.; M-P. Debray; Danel, C.; R. Borie

    2011-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 9...

  20. 64. Study on the DNA damage induced by coal tar pitch fume extracts in rat alveolar macrophage and it's mechanism

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The carcinogenic mechanism of coal tar pitch (CTP) as a recognized carcinogen has been studying. It is widely believed that the carcinogenicity of CTP is based on the genotoxicity of CTP. In the process of carcinogenesis caused by extrinsic chemical substance, the DNA damage mainly occurred in the initiation phase. UP to now, the most sensitive detecting endpoint for DNA damage is to detect DNA single strand breaks. The single cell gel electrophoresis has been rapidly becoming a widely used analytical procedure during the last few years, which can detect DNA strand breaks. The method is a fast, relatively inexpensive, easy to perform, non-radioactive, and very sensitive method. This method suits to different tests in vitro or in vivo. Virtually any eukaryotic cell, which could be made into single cell suspensions, can be processed for analysis of DNA damage using the single cell gel electrophoresis. The aim of the study is to investigate the role of DNA damage induced by CTP fume in rat AM, to examine the changes of ROS, MDA and SOD, and to explore the mechanism of DNA damage by CTP fume. The present study is in favor of studying the mechanism of mutagenesis and carcinogenesis induced by CTP. Method: The healthy male Wistar rats were anesthetized intraperitoneally with 40 mg pentobarbital sodium per kilogram of body weight. The animals were exanguinated by excising femoral, and collected the rat alveolar macrophage by Joseph's method. The concentration of AM had been regulated to 1.5×106 cell/ml. AMs, which had been cultured in 24-well culture plate, were divided into 4 groups. These cells were exposured to 5.0 μg/ml extracts of coal tar pitch fume, and contacted with 500 μM, 1 000 μM, and 2 000 μM of GSH respectively. These cells were divided into 4 groups. After incubation 24 hours, the indexes that had been used above were measured. Results: ①The DNA strand breaks induced by coal tar pitch fume extracts: After undergoing electrophoresis, the

  1. Macrophage-stimulating protein differently affects human alveolar macrophages from smoker and non-smoker patients: evaluation of respiratory burst, cytokine release and NF-kappaB pathway.

    Science.gov (United States)

    Gunella, Gabriele; Bardelli, Claudio; Amoruso, Angela; Viano, Ilario; Balbo, Piero; Brunelleschi, Sandra

    2006-06-01

    Macrophage activation is a key feature of inflammatory reactions occurring during bacterial infections, immune responses and tissue injury. We previously demonstrated that human macrophages of different origin express the tyrosine kinase receptor recepteur d'origine nantaise, the human receptor for MSP (RON) and produce superoxide anion (O(2)(-)) when challenged with macrophage-stimulating protein (MSP), the endogenous ligand for RON. This study was aimed to evaluate the role of MSP in alveolar macrophages (AM) isolated from healthy volunteers and patients with interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis), either smokers or non-smokers, by evaluating the respiratory burst, cytokine release and nuclear factor-kappa B (NF-kappaB) activation. MSP effects were compared with those induced by known AM stimuli, for example, phorbol myristate acetate, N-formyl-methionyl-leucyl-phenylalanine, lipopolysaccharide.MSP evokes O(2)(-) production, cytokine release and NF-kappaB activation in a concentration-dependent manner. By evaluating the respiratory burst, we demonstrate a significantly increased O(2)(-) production in AM from healthy smokers or smokers with pulmonary fibrosis, as compared to non-smokers, thus suggesting MSP as an enhancer of cigarette smoke toxicity. Besides inducing interleukin-1 beta (IL-1beta) and interleukin-10 (IL-10) production, MSP triggers an enhanced tumor necrosis factor-alpha release, especially in healthy and pulmonary fibrosis smokers. On the contrary, MSP-induced IL-10 release is higher in AM from healthy non-smokers. MSP activates the transcription factor NF-kappaB; this effect is more potent in healthy and fibrosis smokers (2.5-fold increase in p50 subunit translocation). This effect is receptor-mediated, as it is prevented by a monoclonal anti-human MSP antibody. The higher effectiveness of MSP in AM from healthy smokers and patients with pulmonary fibrosis is suggestive of its role in these clinical conditions

  2. Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF α mediators

    International Nuclear Information System (INIS)

    Uranium compounds are widely used in the nuclear fuel cycle, military and many other diverse industrial processes. Health risks associated with uranium exposure include nephrotoxicity, cancer, respiratory, and immune disorders. Macrophages present in body tissues are the main cell type involved in the internalization of uranium particles. To better understand the pathological effects associated with depleted uranium (DU) inhalation, we examined the metabolic activity, phagocytosis, genotoxicity and inflammation on DU-exposed rat alveolar macrophages (12.5–200 μM). Stability and dissolution of DU could differ depending on the dissolvent and in turn alter its biological action. We dissolved DU in sodium bicarbonate (NaHCO3 100 mM) and in what we consider a more physiological vehicle resembling human internal media: sodium chloride (NaCl 0.9%). We demonstrate that uranyl nitrate in NaCl solubilizes, enters the cell, and elicits its cytotoxic effect similarly to when it is diluted in NaHCO3. We show that irrespective of the dissolvent employed, uranyl nitrate impairs cell metabolism, and at low doses induces both phagocytosis and generation of superoxide anion (O2−). At high doses it provokes the secretion of TNFα and through all the range of doses tested, apoptosis. We herein suggest that at DU low doses O2− may act as the principal mediator of DNA damage while at higher doses the signaling pathway mediated by O2− may be blocked, prevailing damage to DNA by the TNFα route. The study of macrophage functions after uranyl nitrate treatment could provide insights into the pathophysiology of uranium‐related diseases. -- Highlights: ► Uranyl nitrate effect on cultured macrophages is linked to the doses and independent of its solubility. ► At low doses uranyl nitrate induces generation of superoxide anion. ► At high doses uranyl nitrate provokes secretion of TNFα. ► Uranyl nitrate induces apoptosis through all the range of doses tested.

  3. Role of lysosomal enzymes released by alveolar macrophages in the pathogenesis of the acute phase of hypersensitivity pneumonitis

    Directory of Open Access Journals (Sweden)

    J. L. Pérez-Arellano

    1995-01-01

    Full Text Available Hydrolytic enzymes are the major constituents of alveolar macrophages (AM and have been shown to be involved in many aspects of the inflammatory pulmonary response. The aim of this study was to evaluate the role of lysosomal enzymes in the acute phase of hypersensitivity pneumonitis (HPs. An experimental study on AM lysosomal enzymes of an HP-guinea-pig model was performed. The results obtained both in vivo and in vitro suggest that intracellular enzymatic activity decrease is, at least partly, due to release of lysosomal enzymes into the medium. A positive but slight correlation was found between extracellular lysosomal activity and four parameters of lung lesion (lung index, bronchoalveolar fluid total (BALF protein concentration, BALF LDH and BALF alkaline phosphatase activities. All the above findings suggest that the AM release of lysosomal enzymes during HP is a factor involved, although possibly not the only one, in the pulmonary lesions appearing in this disease.

  4. Functional consequences for primary human alveolar macrophages following treatment with long, but not short, multiwalled carbon nanotubes

    Directory of Open Access Journals (Sweden)

    Sweeney S

    2015-04-01

    Full Text Available Sinbad Sweeney, Davide Grandolfo, Pakatip Ruenraroengsak, Teresa D TetleyLung Cell Biology, Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London, London, UKPurpose: Multiwalled carbon nanotubes (MWCNTs are a potential human health hazard, primarily via inhalation. In the lung, alveolar macrophages (AMs provide the first line of immune cellular defense against inhaled materials. We hypothesized that, 1 and 5 days after treating AMs with short (0.6 µm in length; MWCNT-0.6 µm and long (20 µm in length; MWCNT-20 µm MWCNTs for 24 hours, AMs would exhibit increased markers of adverse bioreactivity (cytokine release and reactive oxygen species generation while also having a modified functional ability (phagocytosis and migration.Methods: Primary human AMs were treated with short and long MWCNTs for 24 hours, 1 and 5 days after which toxicity end points, including cell death, reactive oxygen species generation, and inflammatory mediator release, were measured. AM functional end points involving phagocytic ability and migratory capacity were also measured.Results: AM viability was significantly decreased at 1 and 5 days after treatment with MWCNT-20 µm, while superoxide levels and inflammatory mediator release were significantly increased. At the same time, there was reduced phagocytosis and migratory capacity alongside increased expression of MARCO; this coincided with frustrated phagocytosis observed by scanning electron microscopy. In contrast, the adverse bioreactivity of the shorter MWCNT-0.6 µm with AMs (and any resulting reduction in AM functional ability was substantially less marked or absent altogether.Conclusion: This study shows that after 24-hour treatment with long, but not short, MWCNTs, AM function is severely affected up to 5 days after the initial exposure. This has potentially significant pathophysiological consequences for individuals who may be intentionally (via therapeutic

  5. Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

    Science.gov (United States)

    Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

    1993-01-01

    It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components.

  6. SP-D counteracts GM-CSF-mediated increase of granuloma formation by alveolar macrophages in lysinuric protein intolerance

    Directory of Open Access Journals (Sweden)

    Grasemann Hartmut

    2009-12-01

    Full Text Available Abstract Background Pulmonary alveolar proteinosis (PAP is a syndrome with multiple etiologies and is often deadly in lysinuric protein intolerance (LPI. At present, PAP is treated by whole lung lavage or with granulocyte/monocyte colony stimulating factor (GM-CSF; however, the effectiveness of GM-CSF in treating LPI associated PAP is uncertain. We hypothesized that GM-CSF and surfactant protein D (SP-D would enhance the clearance of proteins and dying cells that are typically present in the airways of PAP lungs. Methods Cells and cell-free supernatant of therapeutic bronchoalveolar lavage fluid (BALF of a two-year-old patient with LPI were isolated on multiple occasions. Diagnostic BALF samples from an age-matched patient with bronchitis or adult PAP patients were used as controls. SP-D and total protein content of the supernatants were determined by BCA assays and Western blots, respectively. Cholesterol content was determined by a calorimetic assay or Oil Red O staining of cytospin preparations. The cells and surfactant lipids were also analyzed by transmission electron microscopy. Uptake of Alexa-647 conjugated BSA and DiI-labelled apoptotic Jurkat T-cells by BAL cells were studied separately in the presence or absence of SP-D (1 μg/ml and/or GM-CSF (10 ng/ml, ex vivo. Specimens were analyzed by light and fluorescence microscopy. Results Here we show that large amounts of cholesterol, and large numbers of cholesterol crystals, dying cells, and lipid-laden foamy alveolar macrophages were present in the airways of the LPI patient. Although SP-D is present, its bioavailability is low in the airways. SP-D was partially degraded and entrapped in the unusual surfactant lipid tubules with circular lattice, in vivo. We also show that supplementing SP-D and GM-CSF increases the uptake of protein and dying cells by healthy LPI alveolar macrophages, ex vivo. Serendipitously, we found that these cells spontaneously generated granulomas, ex vivo, and GM

  7. Single-Cell Mechanics Provides an Effective Means To Probe in Vivo Interactions between Alveolar Macrophages and Silver Nanoparticles.

    Science.gov (United States)

    Liu, Ying X; Karsai, Arpad; Anderson, Donald S; Silva, Rona M; Uyeminami, Dale L; Van Winkle, Laura S; Pinkerton, Kent E; Liu, Gang-yu

    2015-12-10

    Single-cell mechanics, derived from atomic force microscopy-based technology, provides a new and effective means to investigate nanomaterial-cell interactions upon in vivo exposure. Lung macrophages represent initial and important responses upon introducing nanoparticles into the respiratory tract, as well as particle clearance with time. Cellular mechanics has previously proven effective to probe in vitro nanomaterial-cell interactions. This study extends technology further to probe the interactions between primary alveolar macrophages (AM) and silver nanoparticles (AgNPs) upon in vivo exposure. Two types of AgNPs, 20 and 110 nm, were instilled to rat lung at 0.5 mg AgNPs/kg body weight, and allowed 24 h interaction. The consequences of these interactions were investigated by harvesting the primary AMs while maintaining their biological status. Cellular mechanics measurements revealed the diverse responses among AM cells, due to variations in AgNP uptake and oxidative dissolving into Ag(+). Three major responses are evident: zero to low uptake that does not alter cellular mechanics, intracellular accumulation of AgNPs trigger cytoskeleton rearrangement resulting in the stiffening of mechanics, and damage of cytoskeleton that softens the mechanical profile. These effects were confirmed using confocal imaging of F-actin and measurements of reactive oxygen species production. More detailed intracellular interactions will also be discussed on the basis of this study in conjunction with prior knowledge of AgNP toxicity.

  8. Long-Term Persistence of Donor Alveolar Macrophages in Human Lung Transplant Recipients That Influences Donor-Specific Immune Responses.

    Science.gov (United States)

    Nayak, D K; Zhou, F; Xu, M; Huang, J; Tsuji, M; Hachem, R; Mohanakumar, T

    2016-08-01

    Steady-state alveolar macrophages (AMs) are long-lived lung-resident macrophages with sentinel function. Evidence suggests that AM precursors originate during embryogenesis and populate lungs without replenishment by circulating leukocytes. However, their presence and persistence are unclear following human lung transplantation (LTx). Our goal was to examine donor AM longevity and evaluate whether AMs of recipient origin seed the transplanted lungs. Origin of AMs was accessed using donor-recipient HLA mismatches. We demonstrate that 94-100% of AMs present in bronchoalveolar lavage (BAL) were donor derived and, importantly, AMs of recipient origin were not detected. Further, analysis of BAL cells up to 3.5 years post-LTx revealed that the majority of AMs (>87%) was donor derived. Elicitation of de novo donor-specific antibody (DSA) is a major post-LTx complication and a risk factor for development of chronic rejection. The donor AMs responded to anti-HLA framework antibody (Ab) with secretion of inflammatory cytokines. Further, in an experimental murine model, we demonstrate that adoptive transfer of allogeneic AMs stimulated humoral and cellular immune responses to alloantigen and lung-associated self-antigens and led to bronchiolar obstruction. Therefore, donor-derived AMs play an essential role in the DSA-induced inflammatory cascade leading to obliterative airway disease of the transplanted lungs. PMID:27062199

  9. Immortalized MH-S cells lack defining features of primary alveolar macrophages and do not support mouse pneumovirus replication.

    Science.gov (United States)

    Brenner, Todd A; Rice, Tyler A; Anderson, Erik D; Percopo, Caroline M; Rosenberg, Helene F

    2016-04-01

    The SV-40-transformed MH-S cell line maintains some, but not all, features of primary alveolar macrophages (AMs) from BALB/c mice. We show here that MH-S cells produce inflammatory cytokines IL-6 and CXCL10 in response to challenge with Gram-positive Lactobacillus reuteri, and to TLR2 and NOD2 ligands Pam3CSK4 and MDP, respectively. In contrast, although wild-type AMs are infected in vivo by pneumonia virus of mice (PVM), no virus replication was detected in MH-S cells. Interestingly, the surface immunophenotype of MH-S cells (CD11c(+)Siglec F(-)) differs from that of wild-type AMs (CD11c(+) Siglec F(+)) and is similar to that of immature AMs isolated from granulocyte macrophage-colony stimulating factor (GM-CSF) gene-deleted mice; AMs from GM-CSF(-/-) mice also support PVM replication. However, MH-S cells do not express the GM-CSF receptor alpha chain (CD116) and do not respond to GM-CSF. Due to these unusual features, MH-S cells should be used with caution as experimental models of AMs. PMID:26916143

  10. Effects of Bilirubin on Alveolar Macrophages in Rats with Emphysema and Expression of iNOS and NO in Them

    Institute of Scientific and Technical Information of China (English)

    李建强; 赵卉; 宋满景; 徐永健; 张珍祥

    2004-01-01

    To explore the effects of bilirubin on alveolar macrophages (AM) and expression of iNOS and NO in them in emphysema model, the rats were pretreated with bilirubin before exposed to smoke. AM were isolated from bronchoalveolar lavage fluid (BALF) and cultured. Pathological microscopic examination of AM and immunohistochemical analysis of iNOS were performed. Nitric oxide (NO) content in the samples was determined by nitrate reductase technique. The results showed both alveoli and alveolar septum appeared normal in size and shape in normal group. AM showed kidney-shaped nucleus and were rich in Golgi complexes and primary lysosomes in the cytoplasm. The inner membrane of mitochondrion was continuous. Most cristae of the mitochondria were intact. In model group, the alveoli were expanded, ruptured and bullaes were formed. Both the population and sizes of AM increased significantly. Secondary lysosomes were rich in the cytoplasm. Deformation and pyknosis of the nucleus, swelling of the mitochondrions and rupture of the inner mitochondrial membrane could also be seen. At high magnification, most of the mitochondrial cristae were broken, or completely lost at certain points. In bilirubin group, alveoli partly expanded and the population of AM also increased, with morphological changes being slighter than that in model group. Both NO contents and expression of iNOS in model group were higher than those in normal group (P<0.05). In bilirubin group the two indice were lower than those in model group (P<0.05). Our findings suggested that high expression of iNOS and high NO content in AM accelerate the development of emphysema associated with smoking in rats. Bilirubin may exert protective effects on AM and retards the development of emphysema in rats.

  11. Decreased Apoptotic Rate of Alveolar Macrophages of Patients with Idiopathic Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Fotios Drakopanagiotakis

    2012-01-01

    and control group. No difference was found between the respiratory function parameters of the two treatment groups after six months. A positive correlation was found between the number of bcl-2 positive stained macrophages and DLCO after treatment. Conclusions. The decreased apoptotic rate of AM of patients with IPF is not associated with decreased expression of apoptosis mediators involved in the external or internal apoptotic pathway.

  12. Uranyl nitrate-exposed rat alveolar macrophages cell death: Influence of superoxide anion and TNF α mediators

    Energy Technology Data Exchange (ETDEWEB)

    Orona, N.S. [School of Science and Technology, National University of General Martín, Avda Gral Paz 5445 (1650) San Martín, Buenos Aires (Argentina); Tasat, D.R., E-mail: deborah.tasat@unsam.edu.ar [School of Science and Technology, National University of General Martín, Avda Gral Paz 5445 (1650) San Martín, Buenos Aires (Argentina); School of Dentistry, University of Buenos Aires, M. T. de Alvear 2142 (1122), Buenos Aires (Argentina)

    2012-06-15

    Uranium compounds are widely used in the nuclear fuel cycle, military and many other diverse industrial processes. Health risks associated with uranium exposure include nephrotoxicity, cancer, respiratory, and immune disorders. Macrophages present in body tissues are the main cell type involved in the internalization of uranium particles. To better understand the pathological effects associated with depleted uranium (DU) inhalation, we examined the metabolic activity, phagocytosis, genotoxicity and inflammation on DU-exposed rat alveolar macrophages (12.5–200 μM). Stability and dissolution of DU could differ depending on the dissolvent and in turn alter its biological action. We dissolved DU in sodium bicarbonate (NaHCO{sub 3} 100 mM) and in what we consider a more physiological vehicle resembling human internal media: sodium chloride (NaCl 0.9%). We demonstrate that uranyl nitrate in NaCl solubilizes, enters the cell, and elicits its cytotoxic effect similarly to when it is diluted in NaHCO{sub 3}. We show that irrespective of the dissolvent employed, uranyl nitrate impairs cell metabolism, and at low doses induces both phagocytosis and generation of superoxide anion (O{sub 2}{sup −}). At high doses it provokes the secretion of TNFα and through all the range of doses tested, apoptosis. We herein suggest that at DU low doses O{sub 2}{sup −} may act as the principal mediator of DNA damage while at higher doses the signaling pathway mediated by O{sub 2}{sup −} may be blocked, prevailing damage to DNA by the TNFα route. The study of macrophage functions after uranyl nitrate treatment could provide insights into the pathophysiology of uranium‐related diseases. -- Highlights: ► Uranyl nitrate effect on cultured macrophages is linked to the doses and independent of its solubility. ► At low doses uranyl nitrate induces generation of superoxide anion. ► At high doses uranyl nitrate provokes secretion of TNFα. ► Uranyl nitrate induces apoptosis through

  13. Syntaxin 7 and VAMP-7 are Soluble N-Ethylmaleimide–sensitive Factor Attachment Protein Receptors Required for Late Endosome–Lysosome and Homotypic Lysosome Fusion in Alveolar Macrophages

    OpenAIRE

    Ward, Diane McVey; Pevsner, Jonathan; Scullion, Matthew A.; Vaughn, Michael; Kaplan, Jerry

    2000-01-01

    Endocytosis in alveolar macrophages can be reversibly inhibited, permitting the isolation of endocytic vesicles at defined stages of maturation. Using an in vitro fusion assay, we determined that each isolated endosome population was capable of homotypic fusion. All vesicle populations were also capable of heterotypic fusion in a temporally specific manner; early endosomes, isolated 4 min after internalization, could fuse with endosomes isolated 8 min after internalization but not with 12-min...

  14. Toll-like receptor 5 (TLR5), IL-1β secretion, and asparagine endopeptidase are critical factors for alveolar macrophage phagocytosis and bacterial killing.

    OpenAIRE

    Descamps, Delphyne; Mathieu, Le Gars; Balloy, Viviane; Diane, Barbier; Sophia, Maschalidi; Mira, Tohme; Chignard, Michel; Ramphal, Reuben; Bénédicte, Manoury; Sallenave, Jean-Michel

    2012-01-01

    A deficit in early clearance of Pseudomonas aeruginosa (P. aeruginosa) is crucial in nosocomial pneumonia and in chronic lung infections. Few studies have addressed the role of Toll-like receptors (TLRs), which are early pathogen associated molecular pattern receptors, in pathogen uptake and clearance by alveolar macrophages (AMs). Here, we report that TLR5 engagement is crucial for bacterial clearance by AMs in vitro and in vivo because unflagellated P. aeruginosa or different mutants defect...

  15. Study on alveolar macrophage injure caused by uranium dust and its protection

    International Nuclear Information System (INIS)

    Dog's alveolar microphage (AM) obtained by lavage was cultured in vitro. The effects of uranium dust, quartz dust on peroxidation of AM and the effects of magnoliavinin C and VE on bio-membrane was observed. In addition the anti-oxidation effect of VE on the whole body was observed by means of experimental silicosis caused by single dust exposure to trachea. The results demonstrate that two kinds of dust all can induce membrane lipid peroxidation, magnoliavinin C and VE have marked anti-oxidation effect. The administration of VE in vivo demonstrates that VE has effect of inhibiting membrane unsaturated fatty acid peroxidation induced by these two kinds of dust in the ears stage of dust exposure and blocking the chain reaction of free radical so as to retard the pathological developing for silicosis. However it's effect is less than the combining effect of VE and phosphohydroxypipe quinoline. (6 tabs., 12 figs.)

  16. Suppression and recovery of the alveolar macrophage phagocytic system during continuous exposure to 0. 5 ppm ozone

    Energy Technology Data Exchange (ETDEWEB)

    Gilmour, M.I.; Hmieleski, R.R.; Stafford, E.A.; Jakab, G.J. (Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD (USA))

    1991-05-01

    Short-term exposures to ozone (O3) are known to impair pulmonary antibacterial defenses and alveolar macrophage (AM) phagocytosis in a dose-related manner. To determine the effect of prolonged O3 exposure, Swiss mice were exposed continuously to 0.5 ppm O3. At 1, 3, 7, and 14 days, intrapulmonary killing was assessed by inhalation challenge with Staphylococcus aureus or Proteus mirabilis and by comparing the number of viable bacteria remaining in the lungs at 4 h between O3-exposed and control animals. To evaluate the effects of O3 on the functional capacity of the AMs, Fc-receptor mediated phagocytosis was assessed. Ozone exposure impaired the intrapulmonary killing of S. aureus at 1 and 3 days; however, with prolonged exposure, the bactericidal capacity of the lungs returned to normal. This trend of an initial suppression followed by recovery was reflected in the phagocytic capacity of the AMs. In contrast to S. aureus, when P. mirabilis was used as the challenge organism, O3 exposure had no suppressive effect on pulmonary bactericidal activity, which correlated with an increase in the phagocytic cell population in the lungs. Morphologic examination of the lavaged macrophages showed that after 1 day of O3 exposure, the AMs were more foamy, and contained significantly more vacuoles. There was also a significant increase in binucleated cells at 3 days. These studies demonstrate that continuous exposure to O3 modulates AM-dependent lung defenses and points to the importance of the challenge organism and exposure protocol in establishing the adverse effect of O3.

  17. Label-free quantitative phosphoproteomic analysis reveals differentially regulated proteins and pathway in PRRSV-infected pulmonary alveolar macrophages.

    Science.gov (United States)

    Luo, Rui; Fang, Liurong; Jin, Hui; Wang, Dang; An, Kang; Xu, Ningzhi; Chen, Huanchun; Xiao, Shaobo

    2014-03-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an important pathogen of swine worldwide and causes significant economic losses. Through regulating the host proteins phosphorylation, PRRSV was found to manipulate the activities of several signaling molecules to regulate innate immune responses. However, the role of protein phosphorylation during PRRSV infection and the signal pathways responsible for it are relatively unknown. Here liquid chromatography-tandem mass spectrometry for label-free quantitative phosphoproteomics was applied to systematically investigate the global phosphorylation events in PRRSV-infected pulmonary alveolar macrophages. In total, we identified 2125 unique phosphosites, of which the phosphorylation level of 292 phosphosites on 242 proteins and 373 phosphosites on 249 proteins was significantly altered at 12 and 36 h pi, respectively. The phosphoproteomics data were analyzed using ingenuity pathways analysis to identify defined canonical pathways and functional networks. Pathway analysis revealed that PRRSV-induced inflammatory cytokines production was probably due to the activation of mitogen-activated protein kinase and NF-κB signal pathway, which were regulated by several protein kinases during virus infection. Interacting network analysis indicated that altered phosphoproteins were involved in cellular assembly and organization, protein synthesis, molecular transport, and signal transduction in PRRSV infected cells. These pathways and functional networks analysis could provide direct insights into the biological significance of phosphorylation events modulated by PRRSV and may help us elucidate the pathogenic mechanisms of PRRSV infection. PMID:24533505

  18. Interleukin-33 Drives Activation of Alveolar Macrophages and Airway Inflammation in a Mouse Model of Acute Exacerbation of Chronic Asthma

    Directory of Open Access Journals (Sweden)

    Melissa M. Bunting

    2013-01-01

    Full Text Available We investigated the role of interleukin-33 (IL-33 in airway inflammation in an experimental model of an acute exacerbation of chronic asthma, which reproduces many of the features of the human disease. Systemically sensitized female BALB/c mice were challenged with a low mass concentration of aerosolized ovalbumin for 4 weeks to induce chronic asthmatic inflammation and then received a single moderate-level challenge to trigger acute airway inflammation simulating an asthmatic exacerbation. The inflammatory response and expression of cytokines and activation markers by alveolar macrophages (AM were assessed, as was the effect of pretreatment with a neutralizing antibody to IL-33. Compared to chronically challenged mice, AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, together with enhanced expression of proinflammatory cytokines and of cell surface proteins associated with antigen presentation. In parallel, there was markedly increased expression of both mRNA and immunoreactivity for IL-33 in the airways. Neutralization of IL-33 significantly decreased both airway inflammation and the expression of proinflammatory cytokines by AM. Collectively, these data indicate that in this model of an acute exacerbation of chronic asthma, IL-33 drives activation of AM and has an important role in the pathogenesis of airway inflammation.

  19. Differential response to dexamethasone on the TXB2 release in guinea-pig alveolar macrophages induced by zymosan and cytokines

    Directory of Open Access Journals (Sweden)

    M. E. Salgueiro

    1997-01-01

    Full Text Available Glucocorticosteroids reduce the production of inflammatory mediators but this effect may depend on the stimulus. We have compared the time course of the effect of dexamethasone on the thromboxane B2 (TXB2 release induced by cytokine stimulation and zymosan in guinea-pig alveolar macrophages. Interleukin-1β (IL-1β, tumour necrosis factor-α (TNF-α and opsonized zymosan (OZ, all stimulate TXB2 release. High concentrations of dexamethasone (1–10 μM inhibit the TXB2 production induced by both cytokines and OZ, but the time course of this response is different. Four hours of incubation with dexamethasone reduce the basal TXB2 release and that induced by IL-1β and TNF-α, but do not modify the TXB2 release induced by OZ. However, this stimulus was reduced after 24 h incubation. Our results suggest that the antiinflammatory activity of glucocorticosteroids shows some dependence on stimulus and, therefore, may have more than one mechanism involved.

  20. Detection and qualitative identification of mineral fibers and particles in alveolar macrophages of BAL fluid by SEM and EDXA.

    Science.gov (United States)

    Perna, F; Iavarone, M; Skrimpas, S; Mazzarella, G; Sanduzzi, A

    2002-01-01

    Inorganic dust inhalation diseases represent one of the most important chapters in respiratory medicine because of their diagnostic, therapeutic, legal, ecological and social implications. While, in fact, toxic substances inhalation may be easily related to particular occupations, it is more difficult to recognize the potential damage represented by occasional and fortuitous exposition due to pollution of one's living environment. The aim of this study was to suggest a useful investigative method for detecting the presence of mineral substances (dusts and fibers) in the lung in pulmonary fibrosis of uncertain origin. We used scanning electron microscopy (SEM) and semi-quantitative energy-dispersive x-ray microanalysis (EDXA) on broncholaveolar lavage (BAL) and sputum samples of 10 patients, all males, aged 41-66 years, smokers, affected by interstitial lung disease. Two subjects had a negative professional anamnesis while the other 8 declared a potential exposition to inorganic toxic dusts: 2 subjects were involved in the production of asbestos-containing building materials, 2 were miners, 1 a ceramic worker, and 3 insulating materials handlers. Data are reported on the detection of asbestos bodies, vitreous fibers and silica content of alveolar macrophages in BAL fluid. PMID:12619383

  1. Microarray analysis of the effect of Streptococcus equi subsp. zooepidemicus M-like protein in infecting porcine pulmonary alveolar macrophage.

    Directory of Open Access Journals (Sweden)

    Zhe Ma

    Full Text Available Streptococcus equi subsp. zooepidemicus (S. zooepidemicus, which belongs to Lancefield group C streptococci, is an important pathogen of domesticated species, causing septicemia, meningitis and mammitis. M-like protein (SzP is an important virulence factor of S. zooepidemicus and contributes to bacterial infection and antiphagocytosis. To increase our knowledge of the mechanism of SzP in infection, we profiled the response of porcine pulmonary alveolar macrophage (PAM to infection with S. zooepidemicus ATCC35246 wild strain (WD and SzP-knockout strain (KO using the Roche NimbleGen Porcine Genome Expression Array. We found SzP contributed to differential expression of 446 genes, with upregulation of 134 genes and downregulation of 312 genes. Gene Ontology category and KEGG pathway were analyzed for relationships among differentially expressed genes. These genes were represented in a variety of functional categories, including genes involved in immune response, regulation of chemokine production, signal transduction and regulation of apoptosis. The reliability of the data obtained from the microarray was verified by performing quantitative real-time PCR on 12 representative genes. The data will contribute to understanding of SzP mediated mechanisms of S. zooepidemicus pathogenesis.

  2. Uranium induces TNFα secretion and MAPK activation in a rat alveolar macrophage cell line

    International Nuclear Information System (INIS)

    Uranium is a toxic heavy metal found mainly in the nuclear industry, but it is also used in the manufacturing of military munitions. Inhalation studies using animal models have demonstrated that long-term exposure to uranium can lead to the development of neoplasia and fibrosis at the pulmonary level. Because it has been demonstrated that such effects are often associated with inflammation, the effect of uranium on TNFα, IL-1β, and IL-10 synthesis by macrophages was assessed in vitro using the NR8383 cell line. Our results show that a significant TNFα secretion was induced by uranium but not by other metals such as gadolinium. However, IL-1β and IL-10 secretions were unaffected by uranium treatment. TNFα secretion was detectable since 50 μM of uranium and was maximal after 24 h of exposure. Determination of the mechanisms of uranium-induced TNFα production was assessed through the evaluation of protein kinases activation. Our results showed that uranium treatment induced c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) activation. The use of pharmacological inhibitors suggested that both p38 MAPK and protein kinase C (PKC) participate in the signal transduction of uranium-induced TNFα secretion. The regulation of TNFα secretion involves TNFα mRNA accumulation at least through the stabilization of TNFα mRNA, but p38 MAPK did not appear to be involved in this stabilization. However, this observation does not exclude regulation of TNFα synthesis at the transcriptional level, which remains to be demonstrated. Taking together, these results suggest that uranium can induce TNFα secretion by macrophages, thus contributing to a better understanding of the pathological effect of uranium on the lung

  3. SPI-1-encoded type III secretion system of Salmonella enterica is required for the suppression of porcine alveolar macrophage cytokine expression

    Directory of Open Access Journals (Sweden)

    Pavlova Barbora

    2011-01-01

    Full Text Available Abstract Genes localized at Salmonella pathogenicity island-1 (SPI-1 are involved in Salmonella enterica invasion of host non-professional phagocytes. Interestingly, in macrophages, SPI-1-encoded proteins, in addition to invasion, induce cell death via activation of caspase-1 which also cleaves proIL-1β and proIL-18, precursors of 2 proinflammatory cytokines. In this study we were therefore interested in whether SPI-1-encoded type III secretion system (T3SS may influence proinflammatory response of macrophages. To test this hypothesis, we infected primary porcine alveolar macrophages with wild-type S. Typhimurium and S. Enteritidis and their isogenic SPI-1 deletion mutants. ΔSPI1 mutants of both serovars invaded approx. 5 times less efficiently than the wild-type strains and despite this, macrophages responded to the infection with ΔSPI1 mutants by increased expression of proinflammatory cytokines IL-1β, IL-8, TNFα, IL-23α and GM-CSF. Identical macrophage responses to that induced by the ΔSPI1 mutants were also observed to the infection with sipB but not the sipA mutant. The hilA mutant exhibited an intermediate phenotype between the ΔSPI1 mutant and the wild-type S. Enteritidis. Our results showed that the SPI-1-encoded T3SS is required not only for cell invasion but in macrophages also for the suppression of early proinflammatory cytokine expression.

  4. Influence of particle size on drug delivery to rat alveolar macrophages following pulmonary administration of ciprofloxacin incorporated into liposomes.

    Science.gov (United States)

    Chono, Sumio; Tanino, Tomoharu; Seki, Toshinobu; Morimoto, Kazuhiro

    2006-09-01

    In order to confirm the efficacy of ciprofloxacin (CPFX) incorporated into liposomes (CPFX-liposomes) for treatment of respiratory intracellular parasite infections, the influence of particle size on drug delivery to rat alveolar macrophages (AMs) following pulmonary administration of CPFX-liposomes was investigated. CPFX-liposomes were prepared with hydrogenated soybean phosphatidylcholine (HSPC), cholesterol (CH) and dicetylphosphate (DCP) in a lipid molar ratio of 7/2/1 by the hydration method and then adjusted to five different particle sizes (100, 200, 400, 1000 and 2000 nm). In the pharmacokinetic experiment, the delivery efficiency of CPFX to rat AMs following pulmonary administration of CPFX-liposomes increased with the increase in the particle size over the range 100-1000 nm and became constant at over 1000 nm. The concentrations of CPFX in rat AMs until 24 h after pulmonary administration of CPFX-liposomes with a particle size of 1000 nm were higher than the minimum inhibitory concentration of CPFX against various intracellular parasites. In a cytotoxic test, no release of lactate dehydrogenase (LDH) from rat lung tissues by pulmonary administration of CPFX-liposomes with a particle size of 1000 nm was observed. These findings indicate that efficient delivery of CPFX to AMs by CPFX-liposomes with a particle size of 1000 nm induces an excellent antibacterial effect without any cytotoxic effects on lung tissues. Therefore, CPFX-liposomes may be useful in the development of drug delivery systems for the treatment of respiratory infections caused by intracellular parasites, such as Mycobacterium tuberculosis, Chlamydia pneumoniae and Listeria monocytogenes.

  5. Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

    International Nuclear Information System (INIS)

    Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs. On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-α levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later

  6. Differential cell reaction upon Toll-like receptor 4 and 9 activation in human alveolar and lung interstitial macrophages

    Directory of Open Access Journals (Sweden)

    Meyerhans Andreas

    2010-09-01

    Full Text Available Abstract Background Investigations on pulmonary macrophages (MΦ mostly focus on alveolar MΦ (AM as a well-defined cell population. Characteristics of MΦ in the interstitium, referred to as lung interstitial MΦ (IM, are rather ill-defined. In this study we therefore aimed to elucidate differences between AM and IM obtained from human lung tissue. Methods Human AM and IM were isolated from human non-tumor lung tissue from patients undergoing lung resection. Cell morphology was visualized using either light, electron or confocal microscopy. Phagocytic activity was analyzed by flow cytometry as well as confocal microscopy. Surface marker expression was measured by flow cytometry. Toll-like receptor (TLR expression patterns as well as cytokine expression upon TLR4 or TLR9 stimulation were assessed by real time RT-PCR and cytokine protein production was measured using a fluorescent bead-based immunoassay. Results IM were found to be smaller and morphologically more heterogeneous than AM, whereas phagocytic activity was similar in both cell types. HLA-DR expression was markedly higher in IM compared to AM. Although analysis of TLR expression profiles revealed no differences between the two cell populations, AM and IM clearly varied in cell reaction upon activation. Both MΦ populations were markedly activated by LPS as well as DNA isolated from attenuated mycobacterial strains (M. bovis H37Ra and BCG. Whereas AM expressed higher amounts of inflammatory cytokines upon activation, IM were more efficient in producing immunoregulatory cytokines, such as IL10, IL1ra, and IL6. Conclusion AM appear to be more effective as a non-specific first line of defence against inhaled pathogens, whereas IM show a more pronounced regulatory function. These dissimilarities should be taken into consideration in future studies on the role of human lung MΦ in the inflammatory response.

  7. In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts

    International Nuclear Information System (INIS)

    Asbestos-induced mutagenicity in the lung may involve reactive oxygen/nitrogen species (ROS/RNS) released by alveolar macrophages. With the aim of proposing an alternative in vitro mutagenesis test, a co culture system of rat alveolar macrophages (NR8383) and transgenic Big Blue Rat 2 embryonic fibroblasts was developed and tested with a crocidolite sample. Crocidolite exposure induced no detectable increase in ROS production from NR8383, contrasting with the oxidative burst that occurred following a brief exposure (1 hour) to zymosan, a known macrophage activator. In separated co cultures, crocidolite and zymosan induced different changes in the gene expressions involved in cellular inflammation in NR8383 and Big Blue. In particular, both particles induced up-regulation of iNOS expression in Big Blue, suggesting the formation of potentially genotoxic nitrogen species. However, crocidolite exposure in separated or mixed co cultures induced no mutagenic effects whereas an increase in Big Blue mutants was detected after exposure to zymosan in mixed co cultures. NR8383 activation by crocidolite is probably insufficient to induce in vitro mutagenic events. The mutagenesis assay based on the co culture of NR8383 and Big Blue cannot be used as an alternative in vitro method to assess the mutagenic properties of asbestos fibres.

  8. In Vitro Study of Mutagenesis Induced by Crocidolite-Exposed Alveolar Macrophages NR8383 in Cocultured Big Blue Rat2 Embryonic Fibroblasts

    Directory of Open Access Journals (Sweden)

    Yves Guichard

    2010-01-01

    Full Text Available Asbestos-induced mutagenicity in the lung may involve reactive oxygen/nitrogen species (ROS/RNS released by alveolar macrophages. With the aim of proposing an alternative in vitro mutagenesis test, a coculture system of rat alveolar macrophages (NR8383 and transgenic Big Blue Rat2 embryonic fibroblasts was developed and tested with a crocidolite sample. Crocidolite exposure induced no detectable increase in ROS production from NR8383, contrasting with the oxidative burst that occurred following a brief exposure (1 hour to zymosan, a known macrophage activator. In separated cocultures, crocidolite and zymosan induced different changes in the gene expressions involved in cellular inflammation in NR8383 and Big Blue. In particular, both particles induced up-regulation of iNOS expression in Big Blue, suggesting the formation of potentially genotoxic nitrogen species. However, crocidolite exposure in separated or mixed cocultures induced no mutagenic effects whereas an increase in Big Blue mutants was detected after exposure to zymosan in mixed cocultures. NR8383 activation by crocidolite is probably insufficient to induce in vitro mutagenic events. The mutagenesis assay based on the coculture of NR8383 and Big Blue cannot be used as an alternative in vitro method to assess the mutagenic properties of asbestos fibres.

  9. Studies on the biological behaviour of uranium-plutonium mixed oxide aerosols: Inhalation experiments with rats and in vitro studies with alveolar macrophages

    International Nuclear Information System (INIS)

    The retention of spherical and of irregularly shaped (U, Pu) mixed oxides in rat lung was analyzed after inhalation and intratracheal instillation. Their biological behaviour was relatively independent of particle shape and application route with only a few percent of radioactivity being transferred to other organs. In vivo and in vitro uptake and intracellular distribution in rat and bovine alveolar macrophages were analyzed as dependent on various parameters. In addition, detailed electron microscopic studies were performed demonstrating particles within membrane limited vacuoles as well as lying free in the cytoplasm. Under in vitro conditions the uptake process was finished after a few hours. After differential centrifugation of lung or macrophage homogenates the particles sedimented in the first (1000 g) fraction. (orig.)

  10. Preincubation of macrophages alveolar of rate with vitamin C or E attenuate the damage to the plasmatic membrane caused by exhibition to ozone

    International Nuclear Information System (INIS)

    The damaging effects of a 60 minute ozone exposure (0.594 ppm) on the cell membrane of rat alveolar macrophages was assessed by measuring specific release of 51Cr label from the cells. Preincubation of the macrophages in the presence of vitamin C (sodium ascorbate) or vitamine E (DL α tocoferol) prior the ozone exposure significantly diminished 51Cr release. The protective effect of vitamin E was dose dependent. A proposal accounting for the protective effect of vitamins E and C on the cell membrane is presented, and our findings are discussed in relation to recent reports showing that antioxidant supplementation contributes to preserve pulmonary function in ozone-exposed normal and asthmatic volunteers. (Author)

  11. STAT1 Antisense Oligonucleotides Attenuate the Proinflammatory Cytokine Release of Alveolar Macrophages in Bleomycin-Induced Fibrosis

    Institute of Scientific and Technical Information of China (English)

    Xianming Fan; Zengli Wang

    2005-01-01

    To investigate the effect of signal transducers and activators of transcription 1 (STAT1) antisense oligonucleotides (ASON) on concentrations of TNF-α, IL-8, NO secreted by alveolar macrophages (AMs) in bleomycin-induced rat pulmonary fibrosis, five adult female Wistar rats were intratracheally instilled with bleomycin. After 7 days, the rats were killed by right ventricle of heart exsanguinations under ketamine anaesthesia and bronchoalveolar lavage (BAL) was performed to obtain AMs. AMs were divided into four groups, treated with STAT1 ASON, STAT1 sense oligonucleotides (SON), dexamethasone (DEX) and medium alone (control), respectively. AMs and media were collected after culture for 36 h. The mRNA and protein expressions of STAT1 and ICAM-1 in AMs were detected by RT-PCR and ELISA, respectively. The concentrations of TNF-α, IL-8, NO in cultured medium were detected.The STAT1 mRNA expression by AMs in the STAT1 ASON group was lower than those of AMs in the STAT1 SON group, the DEX group and the control group (p < 0.05). Moreover, the STAT1 mRNA expression by AMs in the DEX group was also lower than those of AMs in the STAT1 SON group and the control group (p < 0.05), but the STAT1 mRNA expression by AMs in the STAT1 SON group was not different from that of the control group (p >0.05). The protein expressions of STAT1 and ICAM-1 and the mRNA expression of ICAM-1 showed similar changes to the STAT1 mRNA expression by AMs. The concentrations of TNF-α, IL-8, NO in cultured medium from STAT1 ASON group were lower than those from STAT1 SON, DEX and the control groups (p < 0.05). Moreover,the concentrations of TNF-α, IL-8, NO in cultured medium from DEX group were also lower than those from the control and STAT1 SON group (p < 0.05), but no difference between STAT1 SON group and the control (p > 0.05).The results suggest that STAT1 ASON could inhibit the secretion of TNF-α, IL-8, NO in AMs, and STAT1 could become a target of treating pulmonary fibrosis.

  12. Salmonella Typhimurium induces SPI-1 and SPI-2 regulated and strain dependent downregulation of MHC II expression on porcine alveolar macrophages.

    Science.gov (United States)

    Van Parys, Alexander; Boyen, Filip; Verbrugghe, Elin; Leyman, Bregje; Bram, Flahou; Haesebrouck, Freddy; Pasmans, Frank

    2012-06-13

    Foodborne salmonellosis is one of the most important bacterial zoonotic diseases worldwide. Salmonella Typhimurium is the serovar most frequently isolated from persistently infected slaughter pigs in Europe. Circumvention of the host's immune system by Salmonella might contribute to persistent infection of pigs. In the present study, we found that Salmonella Typhimurium strain 112910a specifically downregulated MHC II, but not MHC I, expression on porcine alveolar macrophages in a Salmonella pathogenicity island (SPI)-1 and SPI-2 dependent way. Salmonella induced downregulation of MHC II expression and intracellular proliferation of Salmonella in macrophages were significantly impaired after opsonization with Salmonella specific antibodies prior to inoculation. Furthermore, the capacity to downregulate MHC II expression on macrophages differed significantly among Salmonella strains, independently of strain specific differences in invasion capacity, Salmonella induced cytotoxicity and altered macrophage activation status. The fact that strain specific differences in MHC II downregulation did not correlate with the extent of in vitro SPI-1 or SPI-2 gene expression indicates that other factors are involved in MHC II downregulation as well. Since Salmonella strain dependent interference with the pig's immune response through downregulation of MHC II expression might indicate that certain Salmonella strains are more likely to escape serological detection, our findings are of major interest for Salmonella monitoring programs primarily based on serology.

  13. Syntaxin 7 and VAMP-7 are soluble N-ethylmaleimide-sensitive factor attachment protein receptors required for late endosome-lysosome and homotypic lysosome fusion in alveolar macrophages.

    Science.gov (United States)

    Ward, D M; Pevsner, J; Scullion, M A; Vaughn, M; Kaplan, J

    2000-07-01

    Endocytosis in alveolar macrophages can be reversibly inhibited, permitting the isolation of endocytic vesicles at defined stages of maturation. Using an in vitro fusion assay, we determined that each isolated endosome population was capable of homotypic fusion. All vesicle populations were also capable of heterotypic fusion in a temporally specific manner; early endosomes, isolated 4 min after internalization, could fuse with endosomes isolated 8 min after internalization but not with 12-min endosomes or lysosomes. Lysosomes fuse with 12-min endosomes but not with earlier endosomes. Using homogenous populations of endosomes, we have identified Syntaxin 7 as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) required for late endosome-lysosome and homotypic lysosome fusion in vitro. A bacterially expressed human Syntaxin 7 lacking the transmembrane domain inhibited homotypic late endosome and lysosome fusion as well as heterotypic late endosome-lysosome fusion. Affinity-purified antibodies directed against Syntaxin 7 also inhibited lysosome fusion in vitro but had no affect on homotypic early endosome fusion. Previous work suggested that human VAMP-7 (vesicle-associated membrane protein-7) was a SNARE required for late endosome-lysosome fusion. A bacterially expressed human VAMP-7 lacking the transmembrane domain inhibited both late endosome-lysosome fusion and homotypic lysosome fusion in vitro. These studies indicate that: 1) fusion along the endocytic pathway is a highly regulated process, and 2) two SNARE molecules, Syntaxin 7 and human VAMP-7, are involved in fusion of vesicles in the late endocytic pathway in alveolar macrophages.

  14. Characterization of part of the toxic effects due to alpha irradiation and to the physico-chemical properties of some actinides. An in vitro study on the alveolar macrophage

    International Nuclear Information System (INIS)

    The aim of this work was to characterize the specific effects due to radiotoxicity of α irradiation and the chemical toxicity of actinides. This was performed on alveolar macrophages extracted from rats and primates by pulmonary lavage. This was done by an in vitro study using either α irradiation from electrodeposited sources, or soluble actinides and lanthanides added to the culture medium. Necrosis and apoptosis induction were quantified after vital staining. For each treatment, cells were studied 1 or 7 days after plating. After either α irradiation or exposure to elements, the main route of death induced was apoptosis. After α irradiation, alveolar macrophages are very radioresistant cells. The observed D0 was between 30 and 100 Gy, depending on the species studied and the time in culture at exposure. In fact, alveolar macrophages irradiated after 1 week in culture have show less radioresistance than those treated after 1 day. The chemical toxicity of Uranium and Neptunium was independent both of time in culture at exposure and the animal species. The threshold we observed were respectively at 5 10-4 and 3 10-6 M. Moreover, within the concentrations studied, Thorium have not shown any toxicity towards alveolar macrophages. 1 day after plating macrophages, lanthanides exerts a higher chemical toxicity than actinides (threshold : 5 10-6 M, Gadolinium, 5 10-5 M, Cerium). These toxicities decreases more than 10 times after exposure 7 days after plating or for primates cells. This phenomenon seems to be due to cell harvesting and/or to cell adaptation to culture. Preliminary results show an impairment of cytokines production, which could be specific of the toxic studied. This was observed at concentrations which appeared non toxic as regards to apoptosis induction. The use of primates alveolar macrophages allow us to extrapolate some of the obtained results to Human. (author)

  15. Stimulation of neoplastic mouse lung cell proliferation by alveolar macrophage-derived, insulin-like growth factor-1 can be blocked by inhibiting MEK and PI3K activation

    Directory of Open Access Journals (Sweden)

    Malkinson Alvin M

    2011-06-01

    Full Text Available Abstract Background Worldwide, lung cancer kills more people than breast, colon and prostate cancer combined. Alterations in macrophage number and function during lung tumorigenesis suggest that these immune effector cells stimulate lung cancer growth. Evidence from cancer models in other tissues suggests that cancer cells actively recruit growth factor-producing macrophages through a reciprocal signaling pathway. While the levels of lung macrophages increase during tumor progression in mouse models of lung cancer, and high pulmonary macrophage content correlates with a poor prognosis in human non-small cell lung cancer, the specific role of alveolar macrophages in lung tumorigenesis is not clear. Methods After culturing either an immortalized lung macrophage cell line or primary murine alveolar macrophages from naïve and lung-tumor bearing mice with primary tumor isolates and immortalized cell lines, the effects on epithelial proliferation and cellular kinase activation were determined. Insulin-like growth factor-1 (IGF-1 was quantified by ELISA, and macrophage conditioned media IGF-1 levels manipulated by IL-4 treatment, immuno-depletion and siRNA transfection. Results Primary macrophages from both naïve and lung-tumor bearing mice stimulated epithelial cell proliferation. The lungs of tumor-bearing mice contained 3.5-times more IGF-1 than naïve littermates, and media conditioned by freshly isolated tumor-educated macrophages contained more IGF-1 than media conditioned by naïve macrophages; IL-4 stimulated IGF-1 production by both macrophage subsets. The ability of macrophage conditioned media to stimulate neoplastic proliferation correlated with media IGF-1 levels, and recombinant IGF-1 alone was sufficient to induce epithelial proliferation in all cell lines evaluated. Macrophage-conditioned media and IGF-1 stimulated lung tumor cell growth in an additive manner, while EGF had no effect. Macrophage-derived factors increased p-Erk1/2, p

  16. Macrophage Metalloelastase: Stretching Therapeutic Opportunities

    Institute of Scientific and Technical Information of China (English)

    Jeannie Q. He; Menno van Lookeren Campagne

    2009-01-01

    While tissue macrophages are at the first line of microbial host defense, they are also convenient hideouts for pathogens escaping immune attack. Houghton et al. discovered that alveolar macrophage mobilizes macrophage metalloelastase to destroy bacteria present inside the cell.

  17. Innate immune response of alveolar macrophage to house dust mite allergen is mediated through TLR2/-4 co-activation.

    Directory of Open Access Journals (Sweden)

    Chia-Fang Liu

    Full Text Available House dust mite, Dermatophagoides pteronyssinus (Der p, is one of the major allergens responsible for allergic asthma. However, the putative receptors involved in the signalization of Der p to the innate immune cells are still poorly defined as well as the impact of their activation on the outcome of the allergen-induced cell response. We previously reported that the HDM activation of mouse alveolar macrophages (AM involves the TLR4/CD14 cell surface receptor complex. Here using a TLR ligand screening essay, we demonstrate that HDM protein extract engages the TLR2, in addition to the TLR4, in engineered TLR-transfected HEK cells but also in the MH-S mouse alveolar macrophage cell line model. Moreover we found that the concomitant recruitment of the MH-S cell's TLR2 and TLR4 receptors by the HDM extract activates the MyD88-dependent signaling pathway and leads to the secretion of the NF-κB regulated pro-inflammatory factors NO and TNF-α. However unlike with the canonical TLR4 ligand (i.e. the bacterial LPS mobilization of TLR4 by the HDM extract induces a reduced production of the IL-12 pro-inflammatory cytokine and fails to trigger the expression of the T-bet transcription factor. Finally we demonstrated that HDM extract down-regulates LPS induced IL-12 and T-bet expression through a TLR2 dependent mechanism. Therefore, we propose that the simultaneous engagement of the TLR2 and TLR4 receptors by the HDM extract results in a cross regulated original activation pattern of the AM which may contribute to the Th2 polarization of the allergen-induced immune response. The deciphering of these cross-regulation networks is of prime importance to open the way for original therapeutic strategies taking advantage of these receptors and their associated signaling pathways to treat allergic asthma.

  18. Syntaxin 7 and VAMP-7 are Soluble N-Ethylmaleimide–sensitive Factor Attachment Protein Receptors Required for Late Endosome–Lysosome and Homotypic Lysosome Fusion in Alveolar Macrophages

    Science.gov (United States)

    Ward, Diane McVey; Pevsner, Jonathan; Scullion, Matthew A.; Vaughn, Michael; Kaplan, Jerry

    2000-01-01

    Endocytosis in alveolar macrophages can be reversibly inhibited, permitting the isolation of endocytic vesicles at defined stages of maturation. Using an in vitro fusion assay, we determined that each isolated endosome population was capable of homotypic fusion. All vesicle populations were also capable of heterotypic fusion in a temporally specific manner; early endosomes, isolated 4 min after internalization, could fuse with endosomes isolated 8 min after internalization but not with 12-min endosomes or lysosomes. Lysosomes fuse with 12-min endosomes but not with earlier endosomes. Using homogenous populations of endosomes, we have identified Syntaxin 7 as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) required for late endosome–lysosome and homotypic lysosome fusion in vitro. A bacterially expressed human Syntaxin 7 lacking the transmembrane domain inhibited homotypic late endosome and lysosome fusion as well as heterotypic late endosome–lysosome fusion. Affinity-purified antibodies directed against Syntaxin 7 also inhibited lysosome fusion in vitro but had no affect on homotypic early endosome fusion. Previous work suggested that human VAMP-7 (vesicle-associated membrane protein-7) was a SNARE required for late endosome–lysosome fusion. A bacterially expressed human VAMP-7 lacking the transmembrane domain inhibited both late endosome–lysosome fusion and homotypic lysosome fusion in vitro. These studies indicate that: 1) fusion along the endocytic pathway is a highly regulated process, and 2) two SNARE molecules, Syntaxin 7 and human VAMP-7, are involved in fusion of vesicles in the late endocytic pathway in alveolar macrophages. PMID:10888671

  19. EFFECTS OF ALVEOLAR MACROPHAGE CONDITIONED MEDIA FROM INTERSTITIAL LUNG DISEASEPATIENTS ON THE PROCOLLAGEN mRNA EXPRESSION IN HUMAN LUNG FIBROBLASTS

    Institute of Scientific and Technical Information of China (English)

    郭子健; 朱元珏; 刘秉慈; 朱亚玲; 赵文理; 陈勇

    1996-01-01

    Progressive inflammation and fibrosis are the central processez in the pathogenesis of pulmonary fibrosis. It is believed that macrophages in areas of chronically inflamed lung play a key role in fibrotic response. Therefore, we investigated the effects of alveolar macrophage (Amφ) conditioned media from interstitial lung disease (ILD) patients on lung fibroblast proliferation and procollagen mRNA expression, After stimulating with Amφ conditioned media from ILD pasients, the fibroblast proliferation increased 71.4% compared with the control, but for media from bronchial carcinoma (BC) patients, it just increased 14.3%. There is a significant dffference between the two groups (P<0. 05). The procollagen αl(I) mRNA in fibroblasts stimulated with Amφ conditioned media from ILD patients was increased 21.3% α1(Ⅲ)was 37.2 higher than control (P<0. 05). It increased 6. 8% and 12.8% fof media from BC patients respectively, but there was no difference when compared to the control. We considered that Amφ from ILD patients might be in an activated state and could release some growth factors to stimulate fibroblast proliferation and promote collagen DNA expression,

  20. In-Depth Global Analysis of Transcript Abundance Levels in Porcine Alveolar Macrophages Following Infection with Porcine Reproductive and Respiratory Syndrome Virus

    Directory of Open Access Journals (Sweden)

    Laura C. Miller

    2010-01-01

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV is a major pathogen of swine worldwide and causes considerable economic loss. Identifying specific cell signaling or activation pathways that associate with variation in PRRSV replication and macrophage function may lead to identification of novel gene targets for the control of PRRSV infection. Serial Analysis of Gene Expression (SAGE was used to create and survey the transcriptome of in vitro mock-infected and PRRSV strain VR-2332-infected porcine alveolar macrophages (PAM at 0, 6, 12, 16, and 24 hours after infection. The transcriptome data indicated changes in transcript abundance occurring in PRRSV-infected PAMs over time after infection with more than 590 unique tags with significantly altered transcript abundance levels identified (P<.01. Strikingly, innate immune genes (whose transcript abundances are typically altered in response to other pathogens or insults including IL-8, CCL4, and IL-1β showed no or very little change at any time point following infection.

  1. Internalization of SiO₂ nanoparticles by alveolar macrophages and lung epithelial cells and its modulation by the lung surfactant substitute Curosurf.

    Science.gov (United States)

    Vranic, Sandra; Garcia-Verdugo, Ignacio; Darnis, Cécile; Sallenave, Jean-Michel; Boggetto, Nicole; Marano, Francelyne; Boland, Sonja; Baeza-Squiban, Armelle

    2013-05-01

    Because of an increasing exposure to environmental and occupational nanoparticles (NPs), the potential risk of these materials for human health should be better assessed. Since one of the main routes of entry of NPs is via the lungs, it is of paramount importance to further characterize their impact on the respiratory system. Here, we have studied the uptake of fluorescently labeled SiO₂ NPs (50 and 100 nm) by epithelial cells (NCI-H292) and alveolar macrophages (MHS) in the presence or absence of pulmonary surfactant. The quantification of NP uptake was performed by measuring cell-associated fluorescence using flow cytometry and spectrometric techniques in order to identify the most suitable methodology. Internalization was shown to be time and dose dependent, and differences in terms of uptake were noted between epithelial cells and macrophages. In the light of our observations, we conclude that flow cytometry is a more reliable technique for the study of NP internalization, and importantly, that the hydrophobic fraction of lung surfactant is critical for downregulating NP uptake in both cell types. PMID:23288678

  2. L-Arginine is not the limiting factor for nitric oxide synthesis by human alveolar macrophages in vitro

    NARCIS (Netherlands)

    Muijsers, RBR; ten Hacken, NHT; Van Ark, [No Value; Folkerts, G; Nijkamp, FP; Postma, DS

    2001-01-01

    Unlike murine mononuclear phagocytes, human macrophages do not release high amounts of nitric oxide (NO) in vitro despite the presence of nitric oxide synthase (NOS). To determine whether this limited NO synthesis in vitro is due to limited availability of the NOS substrate L-arginine, and putative

  3. Avaliação da função de macrófagos alveolares em cavalos clinicamente sadios Evaluation of alveolar macrophage function in healthy horses

    Directory of Open Access Journals (Sweden)

    E. Mori

    2001-04-01

    Full Text Available Devido à importância dos macrófagos alveolares (MA nos mecanismos de defesa pulmonar, foram realizados estudos para avaliar a atividade desses fagócitos em cavalos hígidos. Foram realizados lavados broncoalveolares (LBA em cinco cavalos clinicamente sadios. A citologia foi realizada pela citocentrifugação das amostras e posterior confecção de lâminas coradas pelo método de Rosenfeld. Todas as amostras do LBA foram centrifugadas e a concentração celular foi ajustada para 2×10(6 células/ml, para a mensuração da atividade macrofágica (testes de espraiamento, fagocitose e liberação de peróxido de hidrogênio. A contagem diferencial das células presentes no LBA demonstrou a predominância de macrófagos (59,0± 6,9%. Os resultados obtidos nos testes de mensuração da atividade macrofágica foram: índice de espraiamento 25,1± 19,7%, índice de fagocitose 89,4± 6,2% e liberação de peróxido de hidrogênio 1,6± 0,3nmoles/2×10(5 células (sem PMA - phorbol 12-myristate 13-acetate e 1,8± 0,4nmoles/2×10(5 células (com PMA. Os resultados demonstraram um padrão de atividade para MA de cavalos hígidos, os quais apresentaram índices de ativação mesmo sem elicitação prévia, indicando que as técnicas utilizadas foram adequadas para tal propósito.Due to the importance of alveolar macrophages (AM in pulmonary defense mechanisms, studies were performed in order to evaluate the activity of these cells. Bronchoalveolar lavages (BAL were obtained from five healthy horses, and cytology was performed on glass slides after cytocentrifugation of the samples. Slides were stained by Rosenfeld. All BAL samples were centrifuged and cell concentration was adjusted to 2×10(6 cells/ml, for the measurement of AM activity (spreading, phagocytosis and hydrogen peroxide release tests. Differential counting of the BAL cells demonstrated that macrophages were the predominant type of cell (59.0± 6.9%. Measurement of AM activity presented the

  4. Endothelin receptor-antagonists suppress lipopolysaccharide-induced cytokine release from alveolar macrophages of non-smokers, smokers and COPD subjects.

    Science.gov (United States)

    Gerlach, Kathrin; Köhler-Bachmann, Stefanie; Jungck, David; Körber, Sandra; Yanik, Sarah; Knoop, Heiko; Wehde, Deborah; Rheinländer, Sonja; Walther, Jörg W; Kronsbein, Juliane; Knobloch, Jürgen; Koch, Andrea

    2015-12-01

    Smoking-induced COPD is characterized by chronic airway inflammation, which becomes enhanced by bacterial infections resulting in accelerated disease progression called exacerbation. Alveolar macrophages (AM) release endothelin-1 (ET-1), IL-6, CCL-2 and MMP-9, all of which are linked to COPD pathogenesis and exacerbation. ET-1 signals via ETA- and ETB-receptors (ETAR, ETBR). This is blocked by endothelin receptor antagonists (ERAs), like bosentan, which targets both receptors, ETAR-selective ambrisentan and ETBR-specific BQ788. Therefore, ERAs could have anti-inflammatory potential, which might be useful in COPD and other inflammatory lung diseases. We hypothesized that ERAs suppress cytokine release from AM of smokers and COPD subjects induced by lipopolysaccharide (LPS), the most important immunogen of gram-negative bacteria. AM were isolated from the broncho-alveolar lavage (BAL) of n=29 subjects (11 non-smokers, 10 current smokers without COPD, 8 smokers with COPD), cultivated and stimulated with LPS in the presence or absence of ERAs. Cytokines were measured by ELISA. Endothelin receptor expression was investigated by RT-PCR and western blot. AM expressed ETAR and ETBR mRNA, but only ETBR protein was detected. LPS and ET-1 both induced IL-6, CCL-2 and MMP-9. LPS-induced IL-6 release was increased in COPD versus non-smokers and smokers. Bosentan, ambrisentan and BQ788 all partially reduced all cytokines without differences between cohorts. Specific ETBR inhibition was most effective. LPS induced ET-1, which was exclusively blocked by BQ788. In conclusion, LPS induces ET-1 release in AM, which in turn leads to CCL-2, IL-6 and MMP-9 expression rendering AM sensitive for ERAs. ERAs could have anti-inflammatory potential in smoking-induced COPD.

  5. Recruited alveolar macrophages, in response to airway epithelial-derived monocyte chemoattractant protein 1/CCl2, regulate airway inflammation and remodeling in allergic asthma.

    Science.gov (United States)

    Lee, Yong Gyu; Jeong, Jong Jin; Nyenhuis, Sharmilee; Berdyshev, Evgeny; Chung, Sangwoon; Ranjan, Ravi; Karpurapu, Manjula; Deng, Jing; Qian, Feng; Kelly, Elizabeth A B; Jarjour, Nizar N; Ackerman, Steven J; Natarajan, Viswanathan; Christman, John W; Park, Gye Young

    2015-06-01

    Although alveolar macrophages (AMs) from patients with asthma are known to be functionally different from those of healthy individuals, the mechanism by which this transformation occurs has not been fully elucidated in asthma. The goal of this study was to define the mechanisms that control AM phenotypic and functional transformation in response to acute allergic airway inflammation. The phenotype and functional characteristics of AMs obtained from human subjects with asthma after subsegmental bronchoprovocation with allergen was studied. Using macrophage-depleted mice, the role and trafficking of AM populations was determined using an acute allergic lung inflammation model. We observed that depletion of AMs in a mouse allergic asthma model attenuates Th2-type allergic lung inflammation and its consequent airway remodeling. In both human and mouse, endobronchial challenge with allergen induced a marked increase in monocyte chemotactic proteins (MCPs) in bronchoalveolar fluid, concomitant with the rapid appearance of a monocyte-derived population of AMs. Furthermore, airway allergen challenge of allergic subjects with mild asthma skewed the pattern of AM gene expression toward high levels of the receptor for MCP1 (CCR2/MCP1R) and expression of M2 phenotypic proteins, whereas most proinflammatory genes were highly suppressed. CCL2/MCP-1 gene expression was prominent in bronchial epithelial cells in a mouse allergic asthma model, and in vitro studies indicate that bronchial epithelial cells produced abundant MCP-1 in response to house dust mite allergen. Thus, our study indicates that bronchial allergen challenge induces the recruitment of blood monocytes along a chemotactic gradient generated by allergen-exposed bronchial epithelial cells. PMID:25360868

  6. Motion and twisting of magnetic particles ingested by alveolar macrophages in non-smokers and smokers: Implementation of viscoelasticity

    International Nuclear Information System (INIS)

    Ferrimagnetic iron oxide particles were inhaled by 17 healthy volunteers (9 non-smokers, 8 smokers), and the retained particles were magnetized and detected by a SQUID. Stochastic particle transport due to cytoskeletal reorganizations within macrophages (relaxation) and directed particle motion in a weak magnetic twisting field were investigated with respect to viscous and elastic properties of the cytoskeleton. Relaxation and cytoskeletal stiffness were not influenced by cigarette smoking. Relaxation and particle twisting revealed a non-Newtonian viscosity with a pure viscous and a viscoelastic compartment. Viscous and elastic data obtained from relaxation correlated with particle twisting, indicating that the proposed simple model is a reasonable approximation of cytoskeletal mechanical properties

  7. Efficient drug targeting to rat alveolar macrophages by pulmonary administration of ciprofloxacin incorporated into mannosylated liposomes for treatment of respiratory intracellular parasitic infections.

    Science.gov (United States)

    Chono, Sumio; Tanino, Tomoharu; Seki, Toshinobu; Morimoto, Kazuhiro

    2008-04-01

    The efficacy of pulmonary administration of ciprofloxacin (CPFX) incorporated into mannosylated liposomes (mannosylated CPFX-liposomes) for the treatment of respiratory intracellular parasitic infections was evaluated. In brief, mannosylated CPFX-liposomes with 4-aminophenyl-a-d-mannopyranoside (particle size: 1000 nm) were prepared, and the drug targeting to alveolar macrophages (AMs) following pulmonary administration was examined in rats. Furthermore, the antibacterial and mutant prevention effects of mannosylated CPFX-liposomes in AMs were evaluated by pharmacokinetic/pharmacodynamic (PK/PD) analysis. The targeting efficiency of CPFX to rat AMs following pulmonary administration of mannosylated CPFX-liposomes was significantly greater than that of CPFX incorporated into unmodified liposomes (unmodified CPFX-liposomes; particle size: 1000 nm). According to PK/PD analysis, the mannosylated CPFX-liposomes exhibited potent antibacterial effects against many bacteria although unmodified CPFX-liposomes were ineffective against several types of bacteria, and the probability of microbial mutation by mannosylated CPFX-liposomes was extremely low. The present study indicates that mannosylated CPFX-liposomes as pulmonary administration system could be useful for the treatment of respiratory intracellular parasitic infections.

  8. Distribution characteristics of clarithromycin and azithromycin, macrolide antimicrobial agents used for treatment of respiratory infections, in lung epithelial lining fluid and alveolar macrophages.

    Science.gov (United States)

    Togami, Kohei; Chono, Sumio; Morimoto, Kazuhiro

    2011-10-01

    The distribution characteristics of clarithromycin (CAM) and azithromycin (AZM), macrolide antimicrobial agents, in lung epithelial lining fluid (ELF) and alveolar macrophages (AMs) were evaluated. In the in vivo animal experiments, the time-courses of the concentrations of CAM and AZM in ELF and AMs following oral administration (50 mg/kg) to rats were markedly higher than those in plasma, and the area under the drug concentration-time curve (AUC) ratios of ELF/plasma of CAM and AZM were 12 and 2.2, and the AUC ratios of AMs/ELF were 37 and 291, respectively. In the in vitro transport experiments, the basolateral-to-apical transport of CAM and AZM through model lung epithelial cell (Calu-3) monolayers were greater than the apical-to-basolateral transport. MDR1 substrates reduced the basolateral-to-apical transport of CAM and AZM. In the in vitro uptake experiments, the intracellular concentrations of CAM and AZM in cultured AMs (NR8383) were greater than the extracellular concentrations. The uptake of CAM and AZM by NR8383 was inhibited by ATP depletors. These data suggest that the high distribution of CAM and AZM to AMs is due to the sustained distribution to ELF via MDR1 as well as the high uptake by the AMs themselves via active transport mechanisms.

  9. Efficient drug delivery to alveolar macrophages and lung epithelial lining fluid following pulmonary administration of liposomal ciprofloxacin in rats with pneumonia and estimation of its antibacterial effects.

    Science.gov (United States)

    Chono, Sumio; Tanino, Tomoharu; Seki, Toshinobu; Morimoto, Kazuhiro

    2008-10-01

    The efficacy of pulmonary administration of liposomal ciprofloxacin (CPFX) in pneumonia was evaluated. In brief, the pharmacokinetics following pulmonary administration of liposomal CPFX (particle size, 1,000 nm; dose, 200 microg/kg) were examined in rats with lipopolysaccharide-induced pneumonia as an experimental pneumonia model. Furthermore, the antibacterial effects of liposomal CPFX against the pneumonic causative organisms were estimated by pharmacokinetic/pharmacodynamic (PK/PD) analysis. The time-courses of the concentration of CPFX in alveolar macrophages (AMs) and lung epithelial lining fluid (ELF) following pulmonary administration of liposomal CPFX to rats with pneumonia were markedly higher than that following the administration of free CPFX (200 microg/kg). The time course of the concentrations of CPFX in plasma following pulmonary administration of liposomal CPFX was markedly lower than that in AMs and ELF. These results indicate that pulmonary administration of liposomal CPFX was more effective in delivering CPFX to AMs and ELF compared with free CPFX, and it avoids distribution of CPFX to the blood. According to PK/PD analysis, the liposomal CPFX exhibited potent antibacterial effects against the causative organisms of pneumonia. This study indicates that pulmonary administration of CPFX could be an effective technique for the treatment of pneumonia.

  10. Distribution characteristics of telithromycin, a novel ketolide antimicrobial agent applied for treatment of respiratory infection, in lung epithelial lining fluid and alveolar macrophages.

    Science.gov (United States)

    Togami, Kohei; Chono, Sumio; Seki, Toshinobu; Morimoto, Kazuhiro

    2009-01-01

    The distribution characteristics of telithromycin (TEL), a novel ketolide antimicrobial agent, in lung epithelial fluid (ELF) and alveolar macrophages (AMs) were evaluated. In vivo animal experiments, the time-courses of the concentrations of TEL in ELF and AMs following oral administration of TEL solution (50 mg/4 mL/kg) to rats were markedly higher than in plasma, and areas under drug concentration-time curve (AUC) ratios of ELF/plasma and AMs/plasma were 2.4 and 65.3, respectively. In vitro transport experiments, the basolateral-to-apical transport of TEL through model lung epithelial cell (Calu-3) monolayers was greater than apical-to-basolateral transport. Rhodamine123 and verapamil, MDR1 substrates, reduced the basolateral-to-apical transport of TEL. In vitro uptake experiments, the intracellular equilibrated concentration of TEL in cultured AMs (NR8383) was approximately 40 times the extracellular concentration. The uptake of TEL by NR8383 was inhibited by rotenone and FCCP, ATP depletors and was temperature-dependent. These data suggest that the high distribution of TEL to AMs is due to the sustained distribution to ELF via MDR1 as well as the high uptake by AMs themselves via active transport mechanisms.

  11. Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo

    Directory of Open Access Journals (Sweden)

    Ping Zhou, Shanli Zhai, Xiang Zhou, Ping Lin, Tengfei Jiang, Xueying Hu, Yunbo Jiang, Bin Wu, Qingde Zhang, Xuewen Xu, Jin-ping Li, Bang Liu

    2011-01-01

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV infects mainly the porcine alveolar macrophages (PAMs and causes porcine reproductive and respiratory syndrome (PRRS. Previous studies have analyzed the global gene expression profiles of lung tissue in vivo and PAMs in vitro following infection with PRRSV, however, transcriptome-wide understanding of the interaction between highly pathogenic PRRSV (HP-PRRSV and PAMs in vivo has not yet been established. In this study, we employed Affymetrix microarrays to investigate the gene expression patterns of PAMs isolated from Tongcheng piglets (a Chinese indigenous breed after infection with HP-PRRSV. During the infection, Tongcheng piglets exhibited typical clinical signs, e.g. fever, asthma, coughing, anorexia, lethargy and convulsion, but displayed mild regional lung damage at 5 and 7 dpi. Microarray analysis revealed that HP-PRRSV infection has affected PAMs in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. Several potential antiviral strategies might be employed in PAMs, including upregulating IFN-induced genes and increasing intracellular zinc ion concentration. And inhibition of the complement system likely attenuated the lung damage during HP-PRRSV infection. Transcriptomic analysis of PAMs in vivo could lead to a better understanding of the HP-PRRSV-host interaction, and to the identification of novel antiviral therapies and genetic components of swine tolerance/susceptibility to HP-PRRS.

  12. Susceptibility to Aspergillus Infections in Rats with Chronic Obstructive Pulmonary Disease via Deficiency Function of Alveolar Macrophages and Impaired Activation of TLR2.

    Science.gov (United States)

    Wu, Yuting; Xu, Hong; Li, Li; Yuan, Weifeng; Zhang, Deming; Huang, Wenjie

    2016-08-01

    Clinical evidence indicates that patients with severe chronic obstructive pulmonary disease (COPD) are more susceptible to Aspergillus. However, the exact mechanisms underlying this effect are not known. In this study, we used cigarette smoke exposure to generate COPD rat model. colony-forming units (CFU) count assessment and phagocytosis were applied to evaluate the defense function of COPD rats against Aspergillus challenge. ELISA, western blotting, and GST-Rac1 pull-down assays were conducted to determine the expressions of cytokines and TLR2-associated signaling pathway. Our data showed that Aspergillus burdens increased, phagocytosis of Aspergillus as well as the expressions of inflammatory cytokines from alveolar macrophages (AMs) were impaired in COPD rats compared with normal rats. Though TLR2 signaling-related proteins were induced in response to the stimulation of Aspergillus or Pam3csk4 (TLR2 agonist), the activation of TLR2-associated signaling pathway was apparently interfered in rats with COPD, compared to that in normal rats. Taken together, our study demonstrated that COPD caused the deficiency of AMs function and impaired the activation of TLR2/PI3K/Rac 1 signaling pathway, leading to invasion of Aspergillus infection, which also provides a future basis for the infection control in COPD patients. PMID:27312383

  13. Murine iPSC-Derived Macrophages as a Tool for Disease Modeling of Hereditary Pulmonary Alveolar Proteinosis due to Csf2rb Deficiency

    Directory of Open Access Journals (Sweden)

    Adele Mucci

    2016-08-01

    Full Text Available Induced pluripotent stem cells (iPSCs represent an innovative source for the standardized in vitro generation of macrophages (Mφ. We here describe a robust and efficient protocol to obtain mature and functional Mφ from healthy as well as disease-specific murine iPSCs. With regard to morphology, surface phenotype, and function, our iPSC-derived Mφ (iPSC-Mφ closely resemble their counterparts generated in vitro from bone marrow cells. Moreover, when we investigated the feasibility of our differentiation system to serve as a model for rare congenital diseases associated with Mφ malfunction, we were able to faithfully recapitulate the pathognomonic defects in GM-CSF signaling and Mφ function present in hereditary pulmonary alveolar proteinosis (herPAP. Thus, our studies may help to overcome the limitations placed on research into certain rare disease entities by the lack of an adequate supply of disease-specific primary cells, and may aid the development of novel therapeutic approaches for herPAP patients.

  14. Toll-like receptor 5 (TLR5), IL-1β secretion, and asparagine endopeptidase are critical factors for alveolar macrophage phagocytosis and bacterial killing.

    Science.gov (United States)

    Descamps, Delphyne; Le Gars, Mathieu; Balloy, Viviane; Barbier, Diane; Maschalidi, Sophia; Tohme, Mira; Chignard, Michel; Ramphal, Reuben; Manoury, Bénédicte; Sallenave, Jean-Michel

    2012-01-31

    A deficit in early clearance of Pseudomonas aeruginosa (P. aeruginosa) is crucial in nosocomial pneumonia and in chronic lung infections. Few studies have addressed the role of Toll-like receptors (TLRs), which are early pathogen associated molecular pattern receptors, in pathogen uptake and clearance by alveolar macrophages (AMs). Here, we report that TLR5 engagement is crucial for bacterial clearance by AMs in vitro and in vivo because unflagellated P. aeruginosa or different mutants defective in TLR5 activation were resistant to AM phagocytosis and killing. In addition, the clearance of PAK (a wild-type P. aeruginosa strain) by primary AMs was causally associated with increased IL-1β release, which was dramatically reduced with PAK mutants or in WT PAK-infected primary TLR5(-/-) AMs, demonstrating the dependence of IL-1β production on TLR5. We showed that this IL-1β production was important in endosomal pH acidification and in inducing the killing of bacteria by AMs through asparagine endopeptidase (AEP), a key endosomal cysteine protease. In agreement, AMs from IL-1R1(-/-) and AEP(-/-) mice were unable to kill P. aeruginosa. Altogether, these findings demonstrate that TLR5 engagement plays a major role in P. aeruginosa internalization and in triggering IL-1β formation. PMID:22307620

  15. Role of transforming growth factor-β1 in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Irma Lemaire

    1996-01-01

    Full Text Available Activation of alveolar macrophages (AM for tumour necrosis factor production is suppressed initially during the inflammatory response to fibrogenic dusts. We investigated the mechanisms involved in TNF suppression, notably the role of other AM-derived mediators including prostaglandin E2 (PGE2, transforming growth factor-β1 (TGF-β1, and interleukin 6 (IL-6. The action of PGE2 and TGF-β1, on AM was different. At physiologically relevant doses (25–300 pg/ml, PGE2 did not cause significant inhibition of Hpopolysaccharide (Lps-induced TNF release by AM in vitro but stimulated IL-6 (up to six fold, an inhibitor of AM-derived TNT. In contrast, TGF-β1 (0.5–50 ng/ml inhibited both LPS-induced TNT and IL-6 release by 50% but had no effect on PGE2 production by AM. To determine the respective contribution of these different inhibitors in TNF suppression, AM from rats exposed to fibrogenic asbestos for weeks were treated with neutralizing antibody against TGF-β1 or indomethacin, an inhibitor of PGE2 synthesis. Treatment of rat AM with anti-TGF-β1 but not indomethacin, abrogated the observed TNT suppression. These results suggest that an autocrine, TGF-β1-dependent mechanism is involved in the down-regulation of TNF production by rat AM from animals with lung fibrosis.

  16. Pulmonary alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    B. Crestani

    2011-06-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic “crazy paving” pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy or anti-GM-CSF antibodies (rituximab and plasmapheresis are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement.

  17. Alveolar macrophage kinetics after inhalation of 239PuO2 by CBA/Ca mice: Changes in synthesis of DNA

    International Nuclear Information System (INIS)

    For workers in the nuclear industry, the primary route for the entry of radioactive materials into the body is by inhalation, and the rate of clearance of particles from the pulmonary region of the lung is an important factor in determining radiation dose. It is the function of alveolar macrophages (AM) to maintain the sterility of the lung and to remove insoluble particles from the respiratory surfaces and airways. The AM population is not static, and under normal conditions the loss of macrophages from the alvoli via the conducting airways is balanced by renewal. In this investigation the effects of inhaled 239PuO2 (plutonium dioxide) particles on the synthesis of DNA by AM were studied at times up to 77 days after exposure. We also measured the number of cells recovered by bronchoalveolar lavage and the incidence of AM with nuclear aberrations. The latter provides a sensitive indicator of the effects of radiation. One of the earliest effects observed after exposure to 239PuO2 is a reduction in the number of AM recovered by lavage. This reduction is associated with a 3-fold reduction in the proportion of AM undergoing DNA synthesis at early times after exposure. The overall mean pulse labeling index of AM recovered from sham-exposed mice is 1.68%, and no trends is observed with time. At later times after exposure there is a concurrent increase both in the number of AM recovered by lavage and the proportion of AM in the S-phase of the cell cycle. This repopulation of the AM pool is associated with an increase in the incidence of AM with nuclear aberrations. The results of this study are consistent with the theory of an intrapulmonary pool of proliferating macrophages. The depletion of the AM pool and the latency in the induction of nuclear aberrations after exposure to 239PuO2 can be attributed to a radiation-induced inhibition of cell division in addition to interphase death of AM. 57 refs., 4 figs

  18. The evidential value of intra-alveolar haemosiderin-macrophages in cases of sudden infant death syndrome (SIDS).

    Science.gov (United States)

    Kernbach-Wighton, G; Albalooshi, Y; Madea, B

    2012-10-10

    Intra-alveolar deposits of haemosiderin have repeatedly been brought into connection with some diagnostic value, such as markers for previous imposed suffocation, smothering due to Munchausen syndrome by proxy or sudden infant death syndrome (SIDS). This study is based on 104 SIDS cases and 14 controls (causes of death, e.g. inflammatory changes, internal haemorrhages, asphyxia, blunt force trauma or acute toxicity). The SIDS group comprised 44 females (aged 7 days to 12 months) and 60 males (aged 12 days to 16 months 8 days) with the ages of the controls ranging from 2 months 3 days to 47 months. Routine histology samples from the lungs were stained with Prussian blue and haemosiderin foci were counted in 20 hpf for each lung lobe by a pathologist blinded to the cause of death. Results were assigned to one of five categories for haemosiderin positivity. Data were analysed by the Levene-test revealing identical variances in both groups and with a two-sample t-test showing the mean values for haemosiderin counts not being significantly different between SIDS and control groups. Although the sizes of both samples differed considerably it is our opinion that the haemosiderin counts did not show sufficient diagnostic value. This outcome supports the latest results of other comparable investigations. Furthermore, it highlights the necessity to assess carefully positive haemosiderin findings to avoid false suspicion. PMID:22704554

  19. Use of Induced Pluripotent Stem Cells to Recapitulate Pulmonary Alveolar Proteinosis Pathogenesis

    OpenAIRE

    Suzuki, Takuji; Mayhew, Christopher; Sallese, Anthony; Chalk, Claudia; Carey, Brenna C.; Malik, Punam; Wood, Robert E.; Trapnell, Bruce C.

    2014-01-01

    Rationale: In patients with pulmonary alveolar proteinosis (PAP) syndrome, disruption of granulocyte/macrophage colony–stimulating factor (GM-CSF) signaling is associated with pathogenic surfactant accumulation from impaired clearance in alveolar macrophages.

  20. Pulmonary alveolar proteinosis in a cat

    OpenAIRE

    Szatmári, Viktor; Teske, Erik; Peter G. J. Nikkels; Griese, Matthias; de Jong, Pim A.; Grinwis, Guy; Theegarten, Dirk; Veraa, Stefanie; van Steenbeek, Frank G.; Drent, Marjolein; Bonella, Francesco

    2015-01-01

    BACKGROUND: Pulmonary alveolar proteinosis is an extremely rare lung disease in animals and humans. It is characterized by the deposition of a large amount of phospholipoproteinaceous material in the alveoli. There are several possible etiologies, both congenital and acquired. Alveolar macrophages play an important role in the clearance of surfactant. This is the first report of pulmonary alveolar proteinosis in the feline species. CASE PRESENTATION: Pulmonary alveolar proteinosis was diagnos...

  1. Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies

    International Nuclear Information System (INIS)

    In order to better understand how ambient air particulate matter (PM) affect lung health, the two main airway cell types likely to interact with inhaled particles, alveolar macrophages (AM) and airway epithelial cells have been exposed to particles in vitro and followed for endpoints of inflammation, and oxidant stress. Separation of Chapel Hill PM 10 into fine and coarse size particles revealed that the main proinflammatory response (TNF, IL-6, COX-2) in AM was driven by material present in the coarse PM, containing 90-95% of the stimulatory material in PM10. The particles did not affect expression of hemoxygenase-1 (HO-1), a sensitive marker of oxidant stress. Primary cultures of normal human bronchial epithelial cells (NHBE) also responded to the coarse fraction with higher levels of IL-8 and COX-2, than induced by fine or ultrafine PM. All size PM induced oxidant stress in NHBE, while fine PM induced the highest levels of HO-1 expression. The production of cytokines in AM by both coarse and fine particles was blocked by the toll like receptor 4 (TLR4) antagonist E5531 involved in the recognition of LPS and Gram negative bacteria. The NHBE were found to recognize coarse and fine PM through TLR2, a receptor with preference for recognition of Gram positive bacteria. Compared to ambient PM, diesel PM induced only a minimal cytokine response in both AM and NHBE. Instead, diesel suppressed LPS-induced TNF and IL-8 release in AM. Both coarse and fine ambient air PM were also found to inhibit LPS-induced TNF release while silica, volcanic ash or carbon black had no inhibitory effect. Diesel particles did not affect cytokine mRNA induction nor protein accumulation but interfered with the release of cytokine from the cells. Ambient coarse and fine PM, on the other hand, inhibited both mRNA induction and protein production. Exposure to coarse and fine PM decreased the expression of TLR4 in the macrophages. Particle-induced decrease in TLR4 and hyporesponsiveness to LPS

  2. Inhibitory Effect of Oxymatrine on Quartz-induced Secretion of TNF-α by the Pulmonary Alveolar Macrophages in the Fibroblast Proliferation

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To study the inhibitory effect of oxymatrine (OM) on quartz-induced secretion of TNF-α in the fibroblast proliferation, a given amount of quartz powder and OM of different concentrations were put into the media of pure culture containing macrophages. After 24 h of the culture, the TNF-α in the media was measured by double-antibody sandwich ELISA. The TNF-α (10 ng/mL) and OM of different concentrations were added into the media containing the fibroblasts of the 4th generations from neonate rats. The γ values of cAMP and cGMP in fibroblasts were determined by the radioimmunoassay and the concentrations of cAMP and cGMP were calculated according to standard curve.The intracellular Ca2+ was determined by flow cytometry and cell proliferation was detected by MTT.Our results showed that at the concentrations between 200 μg/mL-1600 μg/mL, OM inhibited the secretion of TNF-α by alveolar macrophages (AM) in a dose-dependent manner. Especially, there were significant differences, to various degrees, in the inhibitory effect of OM between the concentration range of 800 μg/mL-1600 μg/mL and the concentration of 10 ng/mL TNF-α. When compared with 10 ng/mL TNF-α, OM of different concentrations could dose-independently increased the level of intracellular cAMP and decreased the level of cGMP, thereby raising the ratio of cAMP/cGMP and lowering the concentrations of intracellular Ca2+. Moreover, OM of 800 μg/mL had the strongest inhibitory effect on cell proliferation and at this concentration, the cAMP/cGMP was highest and Ca2+was at the lowest level. We are led to conclude that OM can antagonize the damaging effect of quartz on the membrane of AM and the effect of TNF-α promoting the proliferation of fibroblasts. It achieves its inhibitory effect on the promoting effect of TNF-α on fibroblast proliferation by elevating the cAMP level and decreasing the release of Ca2+.

  3. Single-Walled Carbon Nanotube (SWCNT-induced interstitial fibrosis in the lungs of rats is associated with increased levels of PDGF mRNA and the formation of unique intercellular carbon structures that bridge alveolar macrophages In Situ

    Directory of Open Access Journals (Sweden)

    Bermudez Edilberto

    2006-11-01

    Full Text Available Abstract Background Nanotechnology is a rapidly advancing industry with many new products already available to the public. Therefore, it is essential to gain an understanding of the possible health risks associated with exposure to nanomaterials and to identify biomarkers of exposure. In this study, we investigated the fibrogenic potential of SWCNT synthesized by chemical vapor deposition using cobalt (Co and molybdenum (Mo as catalysts. Following a single oropharyngeal aspiration of SWCNT in rats, we evaluated lung histopathology, cell proliferation, and growth factor mRNAs at 1 and 21 days post-exposure. Comparisons were made to vehicle alone (saline containing a biocompatible nonionic surfactant, inert carbon black (CB nanoparticles, or vanadium pentoxide (V2O5 as a known inducer of fibrosis. Results SWCNT or CB caused no overt inflammatory response at 1 or 21 days post-exposure as determined by histopathology and evaluation of cells (>95% macrophages in bronchoalveolar lavage (BAL fluid. However, SWCNT induced the formation of small, focal interstitial fibrotic lesions within the alveolar region of the lung at 21 days. A small fraction of alveolar macrophages harvested by BAL from the lungs of SWCNT-exposed rats at 21 days were bridged by unique intercellular carbon structures that extended into the cytoplasm of each macrophage. These "carbon bridge" structures between macrophages were also observed in situ in the lungs of SWCNT-exposed rats. No carbon bridges were observed in CB-exposed rats. SWCNT caused cell proliferation only at sites of fibrotic lesion formation as measured by bromodeoxyuridine uptake into alveolar cells. SWCNT increased platelet-derived growth factor (PDGF-A, PDGF-B, and PDGF-C mRNA levels significantly at 1 day as measured by Taqman quantitative real-time RT-PCR. At 21 days, SWCNT did not increase any mRNAs evaluated, while V2O5 significantly increased mRNAs encoding PDGF-A, -B, and -C chains, PDGF-Rα, osteopontin

  4. ROS production and gene expression in alveolar macrophages exposed to PM(2.5) from Baghdad, Iraq: Seasonal trends and impact of chemical composition.

    Science.gov (United States)

    Hamad, Samera H; Schauer, James J; Antkiewicz, Dagmara S; Shafer, Martin M; Kadhim, Ahmed Kh

    2016-02-01

    The objective of this study was to assess the impact of changes in atmospheric particulate matter (PM) composition on oxidative stress markers in an in-vitro alveolar macrophage (AM) model. Fifty-three PM2.5 samples were collected during a year-long PM sampling campaign in Baghdad, Iraq, a semi-arid region of the country. Monthly composites were analyzed for chemical composition and for biological activity using in-vitro measurements of ROS production and gene expression in the AM model. Twelve genes that were differentially expressed upon PM exposure were identified and their co-associations with the composition of PM2.5 were examined. Ten of those genes were up-regulated in January and April composites; samples which also exhibited high ROS activity and relatively high PM mass concentration. ROS production was statistically correlated with total PM2.5 mass, levoglucosan (a wood burning tracer) and several trace elements of the PM (especially V and Ni, which are associated with oil combustion). The expression of several cytokine genes was found to be moderately associated with PM mass, crustal materials (indication of dusty days or dust storms) and certain metals (e.g. V, Fe and Ni) in the PM. Thus, the ROS activity association with PM2.5, may, in part, be driven by redox-active metals. The antioxidant response genes (Nqo1 and Hmox1) were moderately associated with polyaromatic hydrocarbons (PAHs) and showed a good correlation (r-Pearson of >0.7) with metals linked to vehicle-related emissions (i.e. Cu, Zn and Sb). Examining these associations in a larger sample pool (e.g. daily samples) would improve the power of the analysis and may strengthen the implication of these chemicals in the oxidative stress of biological systems, which could aid in the development of new metrics of PM toxicity. PMID:26618301

  5. Matrine displayed antiviral activity in porcine alveolar macrophages co-infected by porcine reproductive and respiratory syndrome virus and porcine circovirus type 2.

    Science.gov (United States)

    Sun, Na; Sun, Panpan; Lv, Haipeng; Sun, Yaogui; Guo, Jianhua; Wang, Zhirui; Luo, Tiantian; Wang, Shaoyu; Li, Hongquan

    2016-04-15

    The co-infection of porcine reproductive respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) is quite common in clinical settings and no effective treatment to the co-infection is available. In this study, we established the porcine alveolar macrophages (PAM) cells model co-infected with PRRSV/PCV2 with modification in vitro, and investigated the antiviral activity of Matrine on this cell model and further evaluated the effect of Matrine on virus-induced TLR3,4/NF-κB/TNF-α pathway. The results demonstrated PAM cells inoculated with PRRSV followed by PCV2 2 h later enhanced PRRSV and PCV2 replications. Matrine treatment suppressed both PRRSV and PCV2 infection at 12 h post infection. Furthermore, PRRSV/PCV2 co- infection induced IκBα degradation and phosphorylation as well as the translocation of NF-κB from the cytoplasm to the nucleus indicating that PRRSV/PCV2 co-infection induced NF-κB activation. Matrine treatment significantly down-regulated the expression of TLR3, TLR4 and TNF-α although it, to some extent, suppressed p-IκBα expression, suggesting that TLR3,4/NF-κB/TNF-α pathway play an important role of Matrine in combating PRRSV/PCV2 co-infection. It is concluded that Matrine possesses activity against PRRSV/PCV2 co-infection in vitro and suppression of the TLR3,4/NF-κB/TNF-α pathway as an important underlying molecular mechanism. These findings warrant Matrine to be further explored for its antiviral activity in clinical settings.

  6. Pulmonary Alveolar Proteinosis

    Directory of Open Access Journals (Sweden)

    Sandeep M Patel

    2012-01-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a disease of alveolar accumulation of phospholipoproteinaceous material that results in gas exchange impairment leading to dyspnea and alveolar infiltrates. There are three forms of PAP: congenital, acquired and idiopathic; of which the latter two are predominant in the adult population. Previous case studies have found that the acquired form can be secondary to various autoimmune, infectious, malignant and environmental etiologies. Recent advances in the understanding of the pathophysiology of PAP demonstrate that the idiopathic form is due to antigranulocyte macrophage-colony stimulating factor antibodies. Therapeutic targets that replace granulocyte macrophage colony stimulating factor or remove these antibodies are being actively developed. The current standard of care is to perform whole lung lavage on these patients to clear the alveolar space to help improve respiratory physiology. A case of PAP is reported, followed by a literature review on the diagnosis and management of this rare condition with the aim of increasing awareness among physicians when treating patients who present with alveolar infiltrates.

  7. The effect of infection order of porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus on dually infected swine alveolar macrophages

    Directory of Open Access Journals (Sweden)

    Tsai Yi-Chieh

    2012-09-01

    Full Text Available Abstract Background Concurrent infection with porcine circovirus type 2 (PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV is known as one of the major causes for porcine respiratory disease complex (PRDC. Dual infection with PCV2 and PRRSV is consistently to have more severe clinical presentations and pulmonary lesions than infection with PCV2 alone or PRRSV alone. However, it is not known if dual infections with PCV2 and PRRSV in different infection order may lead to different clinical symptoms in the host. To mimic the possible field conditions, swine alveolar macrophages (AMs were inoculated with PCV2 and PRRSV in vitro simultaneously or with one virus 18 h earlier than the other. The cell viability, cytopathic effects, antigen-containing rates, phagocytotic and microbial killing capabilities, cytokine profiles (IL-8, TNF-α, and IFN-α and FasL transcripts were determined, analyzed, and compared to prove the hypothesis. Results A marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level was revealed in AMs inoculated with PCV2 and PRRSV simultaneously and in AMs inoculated with PCV2 first then PRRSV 18 h later, but not in AMs inoculated with PRRSV first then PCV2 18 h later. Transient decrease in phagocytosis but constant reduction in microbicidal capability in AMs in the group inoculated with PCV2 alone and constant decrease in phagocytosis and microbicidal capability in AMs in all PRRSV-inoculated groups were noted. The levels of IL-8, TNF-α, IFN-α, and FasL transcripts in AMs in all groups with dual inoculation of PCV2 and PRRSV were significantly increased regardless of the infection orders as compared with infection by PCV2 alone or PRRSV alone. Conclusions Swine AMs infected with PCV2 first then PRRSV later or infected with PCV2 and PRRSV simultaneously displayed marked reduction in PRRSV antigen-containing rate, cytopathic effect, and TNF-α expression level. The different

  8. Effects of different experimental approaches on the expression of microRNA of alveolar macrophages in rats with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Yu-ting WU

    2016-08-01

    Full Text Available Objective  To compare the different expressions of miRNAs of alveolar macrophages (AM in two chronic obstructive pulmonary disease (COPD models of rat induced by smudging alone or combined with lipopolysaccharide (LPS infusion. Methods  Sixty female Wistar rats were randomly assigned into 4 groups: control group Ⅰ, control group Ⅱ, COPD model group Ⅰ(cigarette smoke exposure alone, CS and COPD model group Ⅱ(cigarette smoke exposure + LPS infusion, CS+LPS. COPD rat models were evaluated by chest CT, lung function test and histopathological examination of lungs. The primary AM were acquired and the RNAs were then extracted after carrying out bronchoalveolar lavage. Three pairs of samples were used for detection of miRNAs expression by the method of miRNA microarray chip. The difference was verified by qRT-PCR analysis on another 5 pairs of samples. Data analysis was performed to find out the significantly differential miRNAs expression profiles in COPD rat models. Results  The chest CT, lung function test and histopathological examination verified the COPD in rats of CS and CS+LPS groups. Compared with control group Ⅰ, the expressions of let-7b-3p, miR-376c-3p and miR-675-5p were down-regulated in CS group with no miRNAs up-regulated. Compared with control group Ⅱ, the expressions of let-7b-3p and miR-675-5p were down-regulated, while the expressions of 11 miRNAs were obviously up-regulated in CS+LPS group as miR-200b-3p, miR665, miR-344b-1-3p, miR-34c-5p, miR-34b-5p, miR-99b-5p, miR-129-1-3p, miR-3557-5p, miR-331-5p, miR-493-5p and miR-200a3p. Conclusions  COPD rat models are established successfully both with CS and CS+LPS. The results of chest CT, lung function test and histopathological examination have shown no significant difference between the two approaches. However, the expressions of miRNAs of AM are significantly different. DOI: 10.11855/j.issn.0577-7402.2016.07.05

  9. Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples.

    Science.gov (United States)

    Dullin, Christian; dal Monego, Simeone; Larsson, Emanuel; Mohammadi, Sara; Krenkel, Martin; Garrovo, Chiara; Biffi, Stefania; Lorenzon, Andrea; Markus, Andrea; Napp, Joanna; Salditt, Tim; Accardo, Agostino; Alves, Frauke; Tromba, Giuliana

    2015-01-01

    Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites. PMID:25537601

  10. Macrophage-epithelial interactions in pulmonary alveoli.

    Science.gov (United States)

    Bhattacharya, Jahar; Westphalen, Kristin

    2016-07-01

    Alveolar macrophages have been investigated for years by approaches involving macrophage extraction from the lung by bronchoalveolar lavage, or by cell removal from lung tissue. Since extracted macrophages are studied outside their natural milieu, there is little understanding of the extent to which alveolar macrophages interact with the epithelium, or with one another to generate the lung's innate immune response to pathogen challenge. Here, we review new evidence of macrophage-epithelial interactions in the lung, and we address the emerging understanding that the alveolar epithelium plays an important role in orchestrating the macrophage-driven immune response. PMID:27170185

  11. Anionic Pulmonary Surfactant Phospholipids Inhibit Inflammatory Responses from Alveolar Macrophages and U937 Cells by Binding the Lipopolysaccharide-interacting Proteins CD14 and MD-2*♦

    OpenAIRE

    Kuronuma, Koji; Mitsuzawa, Hiroaki; Takeda, Katsuyuki; Nishitani, Chiaki; Chan, Edward D.; Kuroki, Yoshio; Nakamura, Mari; Voelker, Dennis R.

    2009-01-01

    Lipopolysaccharide (LPS), derived from Gram-negative bacteria, is a major cause of acute lung injury and respiratory distress syndrome. Pulmonary surfactant is secreted as a complex mixture of lipids and proteins onto the alveolar surface of the lung. Surfactant phospholipids are essential in reducing surface tension at the air-liquid interface and preventing alveolar collapse at the end of the respiratory cycle. In the present study, we determined that palmitoyl-oleoyl-phosphatidylglycerol a...

  12. Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples

    Energy Technology Data Exchange (ETDEWEB)

    Dullin, Christian, E-mail: christian.dullin@med.uni-goettingen.de [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Monego, Simeone dal [Cluster in Biomedicine, AREA Science Park Basovizza, Trieste (Italy); Larsson, Emanuel [Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste) (Italy); University of Trieste, Trieste (Italy); Linköping University, SE-581 83 Linkoeping (Sweden); Mohammadi, Sara [Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste) (Italy); Krenkel, Martin [University of Göttingen, Göttingen (Germany); Garrovo, Chiara; Biffi, Stefania [IRCCS Burlo Garofolo, Trieste (Italy); Lorenzon, Andrea [Cluster in Biomedicine, AREA Science Park Basovizza, Trieste (Italy); Markus, Andrea [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Napp, Joanna [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Max Planck Institute for Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen (Germany); University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Salditt, Tim [University of Göttingen, Göttingen (Germany); Accardo, Agostino [University of Trieste, Trieste (Italy); Alves, Frauke [University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Max Planck Institute for Experimental Medicine, Hermann-Rein-Strasse 3, 37075 Göttingen (Germany); University Medical Center Göttingen, Robert Koch Strasse 40, 37075 Göttingen (Germany); Tromba, Giuliana [Elettra Sincrotrone Trieste, Strada Statale 14, km 163.5 in AREA Science Park, 34149 Basovizza (Trieste) (Italy)

    2015-01-01

    This study presents an approach to increase the sensitivity of lung computed tomography (CT) imaging by utilizing in-line phase contrast CT in combination with single-distance phase-retrieval algorithms and a dedicated image-processing regime. As demonstrated here, functional CT imaging can be achieved for the assessment of both structural alterations in asthmatic mouse lung tissue and the accumulation pattern of instilled barium-sulfate-labelled macrophages in comparison with healthy controls. Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites.

  13. Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples

    International Nuclear Information System (INIS)

    This study presents an approach to increase the sensitivity of lung computed tomography (CT) imaging by utilizing in-line phase contrast CT in combination with single-distance phase-retrieval algorithms and a dedicated image-processing regime. As demonstrated here, functional CT imaging can be achieved for the assessment of both structural alterations in asthmatic mouse lung tissue and the accumulation pattern of instilled barium-sulfate-labelled macrophages in comparison with healthy controls. Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites

  14. Particle-induced indentation of the alveolar epithelium caused by surface tension forces

    OpenAIRE

    Mijailovich, S. M.; Kojic, M.; Tsuda, A.

    2010-01-01

    Physical contact between an inhaled particle and alveolar epithelium at the moment of particle deposition must have substantial effects on subsequent cellular functions of neighboring cells, such as alveolar type-I, type-II pneumocytes, alveolar macrophage, as well as afferent sensory nerve cells, extending their dendrites toward the alveolar septal surface. The forces driving this physical insult are born at the surface of the alveolar air-liquid layer. The role of alveolar surfactant submer...

  15. Primary pulmonary alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    Šarac Sanja

    2012-01-01

    Full Text Available Introduction. Pulmonary alveolar proteinosis is an uncommon disease characterized by the accumulation of surfactant proteins and phospholipids within the alveolar spaces. Acquired disease can be idiopathic (primary and secondary. The prevalence of acquired pulmonary alveolar proteinosis is about 0.37 per 100,000 persons. Common symptoms are dyspnea and cough. Chest X-ray shows bilateral perihilar infiltrates. Open-lung biopsy is the gold standard for the diagnosis. Treatment includes whole-lung lavage, application of granulocyte-macrophage colonystimulating factor and lung transplantation. Case report. We reported a 51 year-old man with primary form of the disease. It was the second case of this extremely rare disease in the past 30 years in our clinic. The symptoms were longlasting dry cough, fever and physical deterioration. Chest Xray revealed bilateral pulmonary infiltrates; computed tomography showed patchy ground-glass opacification with interlobular thickening. The diagnosis was established by open lung biopsy. Additional tests were performed to exclude secondary form of the disease. Conclusion. We presented a rare clinical entity with typical clinical features and clinical and radiological course of the disease, in order to improve differential diagnostic approach to patients with bilateral lung infiltrations. In patients with pulmonary alveolar proteinosis timely diagnosis and adequate treatment can improve a prognosis.

  16. Autoimmune pulmonary alveolar proteinosis co-existing with breast cancer: a case report

    OpenAIRE

    Sawai, Toyomitsu; Umeyama, Yasuhiro; Yoshioka, Sumako; Matsuo, Nobuko; Suyama, Naofumi; Kohno, Shigeru

    2014-01-01

    Introduction Pulmonary alveolar proteinosis is a rare pulmonary disease characterized by excessive alveolar accumulation of surfactant due to defective alveolar clearance by macrophages. There are only a few published case reports of pulmonary alveolar proteinosis occurring in association with solid cancers. To the best of our knowledge, there are no previously reported cases of pulmonary alveolar proteinosis associated with breast cancer. Case presentation A 48-year-old Asian woman, a nonsmo...

  17. The Molecular Basis of Pulmonary Alveolar Proteinosis

    OpenAIRE

    Carey, Brenna; Trapnell, Bruce C.

    2010-01-01

    Pulmonary alveolar proteinosis (PAP) comprises a heterogenous group of diseases characterized by abnormal surfactant accumulation resulting in respiratory insufficiency, and defects in alveolar macrophage- and neutrophil-mediated host defense. Basic, clinical and translational research over the past two decades have raised PAP from obscurity, identifying the molecular pathogenesis in over 90% of cases as a spectrum of diseases involving the disruption of GM-CSF signaling. Autoimmune PAP repre...

  18. Pulmonary alveolar proteinosis: diagnostic and therapeutic challenges

    OpenAIRE

    Campo Ilaria; Kadija Zamir; Mariani Francesca; Paracchini Elena; Rodi Giuseppe; Mojoli Francesco; Braschi Antonio; Luisetti Maurizio

    2012-01-01

    Abstract Pulmonary Alveolar Proteinosis (PAP) is a rare syndrome characterized by pulmonary surfactant accumulation within the alveolar spaces. It occurs with a reported prevalence of 0.1 per 100,000 individuals and in distinct clinical forms: autoimmune (previously referred to as the idiopathic form, represents the vast majority of PAP cases, and is associated with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) auto-antibodies; GMAbs), secondary (is a consequence of underlying dis...

  19. Lung Transplant Recipient with Pulmonary Alveolar Proteinosis

    OpenAIRE

    Tokman, Sofya; Hahn, M. Frances; Abdelrazek, Hesham; Panchabhai, Tanmay S.; Patel, Vipul J.; Walia, Rajat; Omar, Ashraf

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and ...

  20. Efeitos do estresse agudo de contenção, do estresse crônico de natação e da administração de glutamina sobre a liberação de superóxido por macrófagos alveolares de ratos Effects of acute restraint stress, chronic swim stress and glutamine administration on the release of superoxide from alveolar macrophages of rats

    Directory of Open Access Journals (Sweden)

    Elizabeth do Nascimento

    2007-08-01

    Full Text Available OBJETIVO: Avaliar a liberação de ânion superóxido por macrófagos alveolares em ratos submetidos ou não ao estresse agudo, ao exercício físico de natação e à suplementação com glutamina. MÉTODOS: Quarenta e dois ratos machos da linhagem Wistar com idade em torno de 62 (desvio-padrão=3 dias de idade foram divididos em grupos controle, treino, estresse e glutamina. Após a intervenção, macrófagos alveolares foram coletados e estimulados com acetato de formol miristato para a avaliação da liberação de ânion superóxido. RESULTADOS: Em comparação à primeira hora (controle=26,2, desvio-padrão=4,2; treino=28,7, desvio-padrão=5,1; estresse=20,3, desvio-padrão=4,4; glutamina=26,2, desvio-padrão=4,2, houve aumento (pOBJECTIVE: To assess the release of superoxide anion from alveolar macrophages of rats submitted or not to acute restraint stress, forced swimming and glutamine supplementation. METHODS: Forty-two male Wistar rats aging roughly 62 days (standard deviation=3 were randomly divided into four groups: control, training, stress and glutamine. After the intervention, alveolar macrophages were collected and stimulated with phorbol myristate acetate to assess the release of superoxide anion. RESULTS: When compared with the first hour (control=26.2, standard deviation=4.2; training=28.7, standard deviation=5.1; stress=20.3 , standard deviation=4.4; glutamine=26.2, standard deviation=4.2, the release of superoxide increased (p<0.001 in all experimental groups in the second hour (control=38.4, standard deviation=4.9; training=40.7, standard deviation=6.1; stress=30.2, standard deviation=5.6; glutamine=39.2, standard deviation=5.2 of observation. Training and glutamine supplementation did not induce differences in the release of superoxide from alveolar macrophages when compared with the control group. Only the rats submitted to stress showed a reduction in the release of superoxide in both the first (20.3, standard deviation

  1. Lung Collagens Perpetuate Pulmonary Fibrosis via CD204 and M2 Macrophage Activation

    OpenAIRE

    Stahl, Mirjam; Schupp, Jonas; Jäger, Benedikt; Schmid, Michael; Zissel, Gernot; Müller-Quernheim, Joachim; Prasse, Antje

    2013-01-01

    Idiopathic pulmonary fibrosis is characterized by abundant collagen production and accumulation of alternatively activated macrophages (M2) in the lower respiratory tract. Mechanisms as to how alveolar macrophages are activated by collagen breakdown products are unknown. Alveolar macrophages were obtained by bronchoalveolar lavage from 30 patients with idiopathic pulmonary fibrosis (IPF) and 37 healthy donors (HD). Alveolar macrophages were cultured in the presence of collagen type I, III, IV...

  2. Evaluation of alveolar macrophage function after experimental infection with equine herpesvirus-1 in horses Avaliação da função dos macrófagos alveolares após infecção experimental em cavalos por herpesvírus eqüino tipo 1

    Directory of Open Access Journals (Sweden)

    E. Mori

    2003-06-01

    Full Text Available The role of the pulmonary alveolar macrophages (PAM in the lung defense mechanism was evaluated in horses infected with equine hespesvirus-1 (EHV-1. Five adult horses were exposed to 10(6.6 TCID50 EHV-1 by intranasal instillation. Cytology of bronchoalveolar lavage (BAL was performed using cytocentrifugation of samples and slides stained by Rosenfeld. Cell concentration was adjusted to 2´10(6 cells/ml, for the measurement of macrophage activity - spreading, phagocytosis of zymosan particles and release of hydrogen peroxide (H2O2. All animals were positive in virus isolation on the second, third and fifth days post-inoculation (DPI. Seroconversion was observed on the 14th DPI. Lymphocytosis was observed by BAL cytology on the 16th DPI. Measurement of macrophage activity demonstrated a marked increase in the spreading rate, on the 23rd and 30th DPI. Phagocytosis was decreased on the second DPI, and returned to levels similar to those observed before inoculation on the 23rd DPI. The amount of H2O2 released by PAM declined on day 2, but, by day 16, they returned to values similar to those observed before inoculation. The decline in PAM activity in the acute phase of disease is indirect evidence that these cells have an important role in lung defense mechanisms against this agent.O papel dos macrófagos alveolares (MA nos mecanismos de defesa pulmonar foi estudado em cavalos infectados pelo herpesvírus eqüino tipo 1 (EHV-1. Cinco cavalos adultos foram inoculados com 10(6,6 TCID50 do EHV-1, por instilação intranasal. A citologia do lavado broncoalveolar (LBA foi feita usando-se citocentrifugação das amostras e confecção de lâminas coradas por Rosenfeld. A concentração celular foi ajustada para 2´10(6 células/ml, para mensuração da atividade macrofágica - espraiamento, fagocitose de partículas de zymosan e liberação de peróxido de hidrogênio (H2O2. Observou-se soroconversão no 14º dia pós-inoculação (DPI e isolamento viral

  3. Unsuspected pulmonary alveolar proteinosis in a patient with acquired immunodeficiency syndrome: a case report

    OpenAIRE

    Niazi Masooma; DeLaCruz Angel E; Tejwani Dimple; Diaz-Fuentes Gilda

    2011-01-01

    Abstract Introduction Diffuse lung infiltrates are a common finding in patients with acquired immunodeficiency syndrome and causes range from infectious processes to malignancies or interstitial lung diseases. Pulmonary alveolar proteinosis is a rare pulmonary disorder rarely reported in patients infected with human immunodeficiency virus. Secondary pulmonary alveolar proteinosis is associated with conditions involving functional impairment or reduced numbers of alveolar macrophages. It can b...

  4. Serial bronchoscopic lung lavage in pulmonary alveolar proteinosis under local anesthesia.

    Science.gov (United States)

    Davis, K Rennis; Vadakkan, D Thomas; Krishnakumar, E V; Anas, A Muhammed

    2015-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by alveolar accumulation of surfactant composed of proteins and lipids due to defective surfactant clearance by alveolar macrophages. Mainstay of treatment is whole lung lavage, which requires general anesthesia. Herein, we report a case of primary PAP, successfully treated with serial bronchoscopic lung lavages under local anesthesia. PMID:25814803

  5. Serial bronchoscopic lung lavage in pulmonary alveolar proteinosis under local anesthesia

    OpenAIRE

    K Rennis Davis; D Thomas Vadakkan; Krishnakumar, E. V.; A Muhammed Anas

    2015-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease, characterized by alveolar accumulation of surfactant composed of proteins and lipids due to defective surfactant clearance by alveolar macrophages. Mainstay of treatment is whole lung lavage, which requires general anesthesia. Herein, we report a case of primary PAP, successfully treated with serial bronchoscopic lung lavages under local anesthesia.

  6. Serial bronchoscopic lung lavage in pulmonary alveolar proteinosis under local anesthesia

    Directory of Open Access Journals (Sweden)

    K Rennis Davis

    2015-01-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a rare disease, characterized by alveolar accumulation of surfactant composed of proteins and lipids due to defective surfactant clearance by alveolar macrophages. Mainstay of treatment is whole lung lavage, which requires general anesthesia. Herein, we report a case of primary PAP, successfully treated with serial bronchoscopic lung lavages under local anesthesia.

  7. Pulmonary alveolar proteinosis

    Science.gov (United States)

    Alveolar proteinosis; Pulmonary alveolar phospholipoproteinosis ... In some cases, the cause of pulmonary alveolar proteinosis is unknown. In others, it occurs with lung infection or an immune problem. It also can occur with cancers of the blood system, ...

  8. Allergic Lung Inflammation Reduces Tissue Invasion and Enhances Survival from Pulmonary Pneumococcal Infection in Mice, Which Correlates with Increased Expression of Transforming Growth Factor β1 and SiglecF(low) Alveolar Macrophages.

    Science.gov (United States)

    Sanfilippo, Alan M; Furuya, Yoichi; Roberts, Sean; Salmon, Sharon L; Metzger, Dennis W

    2015-07-01

    Asthma is generally thought to confer an increased risk for invasive pneumococcal disease (IPD) in humans. However, recent reports suggest that mortality rates from IPD are unaffected in patients with asthma and that chronic obstructive pulmonary disease (COPD), a condition similar to asthma, protects against the development of complicated pneumonia. To clarify the effects of asthma on the subsequent susceptibility to pneumococcal infection, ovalbumin (OVA)-induced allergic lung inflammation (ALI) was induced in mice followed by intranasal infection with A66.1 serotype 3 Streptococcus pneumoniae. Surprisingly, mice with ALI were significantly more resistant to lethal infection than non-ALI mice. The heightened resistance observed following ALI correlated with enhanced early clearance of pneumococci from the lung, decreased bacterial invasion from the airway into the lung tissue, a blunted inflammatory cytokine and neutrophil response to infection, and enhanced expression of transforming growth factor β1 (TGF-β1). Neutrophil depletion prior to infection had no effect on enhanced early bacterial clearance or resistance to IPD in mice with ALI. Although eosinophils recruited into the lung during ALI appeared to be capable of phagocytizing bacteria, neutralization of interleukin-5 (IL-5) to inhibit eosinophil recruitment likewise had no effect on early clearance or survival following infection. However, enhanced resistance was associated with an increase in levels of clodronate-sensitive, phagocytic SiglecF(low) alveolar macrophages within the airways following ALI. These findings suggest that, while the risk of developing IPD may actually be decreased in patients with acute asthma, additional clinical data are needed to better understand the risk of IPD in patients with different asthma phenotypes. PMID:25964474

  9. Effects of lipopolysaccharide on cytokines secreted by alveolar macrophages in aged rats%脂多糖对衰老大鼠肺泡巨噬细胞分泌细胞因子的影响

    Institute of Scientific and Technical Information of China (English)

    刘焕星; 姜智; 贾玉珍

    2007-01-01

    目的 探讨脂多糖(lipopolysaccharide,LPS)对衰老大鼠模型肺泡巨噬细胞(alveolar macrophage,AM)产生细胞因子的影响. 方法 ①将24只Wistar大鼠随机均分为2组,任取其中1组用D-半乳糖[D-galactose,D-gal,20 mg/(kg·d)]腹腔注射,连续6周制备衰老大鼠模型;另1组青年大鼠作为对照;②应用支气管肺泡灌洗和细胞贴壁的方法获取AM,用瑞氏染色鉴定纯度、台盼蓝染色测定活细胞数;③将各组获取的AM再随机均分为LPS刺激组及阴性对照组,其中LPS刺激组细胞在贴壁 2 h后加入含10 mg/L LPS的1640培养液,24 h后用酶联免疫吸附法(enzyma linked immunosorsent assay,ELISA)分别测定细胞上清液中肿瘤坏死因子-α(tumor necrosis factor-α,TNF- α)和内皮素(endolthelin,ET-1)的含量. 结果 (1)青年、老年大鼠LPS刺激组TNF-α、ET-1均高于对照组;(2)老年LPS刺激组肺泡灌洗液上清中TNF-α[ (31.32±2.38) pg/ml]高于青年LPS刺激组[(25.48±3.52) pg/ml, P《0.05];老年LPS刺激组ET-1[(3.91±0.11) pg/ml] 高于青年LPS刺激组[(3.17±0.11) pg/ml, P《0.05]. 结论 老年大鼠对LPS刺激的反应程度大于青年组,AM在炎症反应中起重要的作用.

  10. Lung Transplant Recipient with Pulmonary Alveolar Proteinosis

    Directory of Open Access Journals (Sweden)

    Sofya Tokman

    2016-01-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF, and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus.

  11. Lung Transplant Recipient with Pulmonary Alveolar Proteinosis.

    Science.gov (United States)

    Tokman, Sofya; Hahn, M Frances; Abdelrazek, Hesham; Panchabhai, Tanmay S; Patel, Vipul J; Walia, Rajat; Omar, Ashraf

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus. PMID:27213073

  12. Expression of RBD-2 in alveolar macrophages of diabetic rats regulated by LPS%脂多糖LPS对糖尿病大鼠肺泡巨噬细胞RBD-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    张伟义; 朱涛

    2011-01-01

    目的 以肺泡巨噬细胞为研究对象,现察脂多糖(lipopolysaccharide,LPS)刺激下RBD-2(大鼠β防御素-2,Rat β-defensins-2)在正常大鼠及糖尿病大鼠肺泡巨噬细胞表达的变化.方法 以健康雄性SD大鼠制备糖尿病模型.32只大鼠随机分为四组:正常对照组(A组)、耱尿病组(B组)、LPS组(C组)和糖尿病+LPS组(D组),每组均为8只.分离培养大鼠肺泡巨噬细胞,通过RT-PCR以及Western blotting分别检测RBD-2的RNA及蛋白质表达水平,同时通过Real Time PCR检测大鼠肺泡巨噬细胞的TLR-2以及TLR-4的mRNA的表达.结果 大鼠耱尿病模型构建成功.RT-PCR以及Western blotting结果显示,与正常组相比,糖尿病组、正常组+LPS组、糖尿病十脂多糖组的RBD-2 mRNA以及蛋白质表达水平依次增加,差异显著(P<0.05).Real Time PCR结果显示,与正常组相比,糖尿病组、正常组+ LPS组、糖尿病十脂多糖组的TLR-4 mRNA的表达水平依次增加,差异显著(P<0.05),而TLR-2差异则不明显.结论 LPS刺激后糖尿病大鼠肺泡巨噬细胞RBD-2表达增加较糖尿病组更为显著,说明RBD-2变化对于增强糖尿病机体的非特异性免疫能力具有明显的帮助,同时糖尿病大鼠肺泡巨噬细胞RBD-2表达较正常组增高,说明处于耱尿病时期的大鼠机体处于炎症状态,并且这一通路的表达受体主要是TLR-4受体.%Objective To observe the expression of rat β-defensin 2 (RBD-2) in alveolar macrophages of diabetic rats after lipopolysaccharide (LPS) stimulation. Methods Healthy SD rats were used to construct the diabetic models. Then they were randomly divided into four groups. Group A: the control group; Group B; the diabetic group; Group C; the LPS stimulated group; Group D; the diabetic group with LPS infection. Rat alveolar macrophages were captured and cultured. The RT-PCR and Western blotting method were utilized to detect the mRNA and protein level of RBD-2. The Real Time PCR

  13. Macrophage reprogramming by mycolic acid promotes a tolerogenic response in experimental asthma

    NARCIS (Netherlands)

    Korf, Johanna E.; Pynaert, Gwenda; Tournoy, Kurt; Boonefaes, Tom; Van Oosterhout, Antoon; Ginneberge, Daisy; Haegeman, Anuschka; Verschoor, Jan A.; De Baetselier, Patrick; Grooten, Johan

    2006-01-01

    Rationale: Mycolic acid (MA) constitutes a major and distinguishing cell wall biolipid from Mycobacterium tuberculosis. MA interferes with the lipid homeostasis of alveolar macrophages, inducing differentiation into foamy macrophages exhibiting increased proinflammatory function. Objectives: We veri

  14. Mechanisms of macrophage accumulation in the lungs of asbestos-exposed subjects

    International Nuclear Information System (INIS)

    Chronic asbestos exposure is associated with the accumulation of mononuclear phagocytes in the lower respiratory tract. This process can be both protective and injurious, since macrophages can aid in asbestos clearance yet also modulate structural derangements of the alveolar walls. To understand why macrophages accumulate in the lungs of asbestos-exposed persons, 2 possible mechanisms were evaluated using alveolar macrophages from subjects with histories of chronic high exposure to airborne asbestos: enhanced recruitment of blood monocytes to the lung, and an increased rate of replication of macrophages in situ. Monoclonal antibody analysis with antibodies that detect surface antigens on the majority of circulating blood monocytes but only on a minority of mature alveolar macrophages demonstrated that an increased proportion of alveolar macrophages of asbestos workers expressed monocyte lineage antigens, suggesting the presence of young newly recruited macrophages and thus enhanced recruitment. Culture of the alveolar macrophages from these subjects with [3H]thymidine followed by autoradiography demonstrated an increased proportion of alveolar macrophages synthesizing DNA, suggesting the macrophages are replicating at an increased rate in situ. These observations are consistent with the concept that both enhanced recruitment of blood monocytes and increased local proliferation of alveolar macrophages contribute to the accumulation mononuclear phagocytes in the lung of persons with chronic asbestos exposure

  15. Rare Lung Diseases II: Pulmonary Alveolar Proteinosis

    Directory of Open Access Journals (Sweden)

    Stephen C Juvet

    2008-01-01

    Full Text Available The present article is the second in a series on rare lung diseases. It focuses on pulmonary alveolar proteinosis (PAP, a disorder in which lipoproteinaceous material accumulates in the alveolar space. PAP was first described in 1958, and for many years the nature of the material accumulating in the lungs was unknown. Major insights into PAP have been made in the past decade, and these have led to the notion that PAP is an autoimmume disorder in which autoantibodies interfere with signalling through the granulocyte-macrophage colony-stimulating factor receptor, leading to macrophage and neutrophil dysfunction. This has spurred new therapeutic approaches to this disorder. The discussion of PAP will begin with a case report, then will highlight the classification of PAP and review recent insights into the pathogenesis of PAP. The approach to therapy and the prognosis of PAP will also be discussed.

  16. 不同毒力结核杆菌对感染小鼠肺泡巨噬细胞铁蛋白及铁转运蛋白表达的影响%Effect on expression of macrophages ferroportin and ferritin in mouse alveolar macrophages by mycobacterium tuberculosis

    Institute of Scientific and Technical Information of China (English)

    庄睿; 李文娟; 梁晨; 樊超; 张万江; 王霞; 张锋; 宝音; 章乐; 吴芳; 吴江东; 张春军; 张辉

    2014-01-01

    目的:探讨不同毒力的结核杆菌分别感染小鼠肺泡巨噬细胞后铁蛋白( Fn)和铁转运蛋白( FPN)表达量及其时相性变化。方法:利用制备的结核杆菌国际标准强毒株H37Rv株(以下简称H37Rv株)和卡介苗菌株(以下简称BCG)菌悬液,分别经小鼠尾静脉注射,建立各组小鼠感染模型。各组小鼠感染模型建立成功后,分别于第1、3、5、7、9、11、13、15天,进行肺泡灌洗,收集小鼠肺泡灌洗液,获取各组小鼠肺泡巨噬细胞。应用ELISA方法检测各组感染组小鼠肺泡巨噬细胞中Fn和FPN的表达含量;应用Western blot技术检测上述时间点各组感染的小鼠肺泡巨噬细胞内Fn的表达量。结果:用ELISA方法和Western blot技术检测各组小鼠肺泡巨噬细胞内Fn表达,结果显示:于模型建成后第7、9、11天,H37Rv株组与BCG组的小鼠肺泡巨噬细胞内Fn表达量明显减低,并且于第7天时表达量最低,差异有统计学意义(P<0.05)。利用ELISA方法检测各组小鼠肺泡巨噬细胞内FNP的表达,结果显示:不同毒力的结核杆菌菌株感染小鼠肺泡巨噬细胞后,各感染组内小鼠肺泡巨噬细胞FPN随处理时间延长表达逐渐降低;于感染第5天开始下降明显,第7、9天最低。 H37 Rv株组和BCG组表达接近,于第5、7、9天明显低于正常对照组FPN的表达量,差异有统计学意义( P<0.05)。结论:结核杆菌感染导致巨噬细胞内Fn与FPN的表达均降低,并且感染巨噬细胞Fn和FPN的表达与结核杆菌的毒力强弱关系无相关性。%Objective:To discuss the change of ferritin ( Fn) and ferroportin expression quantity and time-related feature in the alveolar macrophages of mice , infected with different virulence of Mycobacterium Tuberculosis infected .Methods:The prepared bacte-ria of H37Rv or BCG were injected intravenously into the mice tails .On the day 1, 3, 5, 7

  17. NOD2 stimulation enhances the innate immunity against Mycobacterium tuberculosis in human alveolar macrophages%NOD2信号对人肺泡巨噬细胞抗结核分枝杆菌活性的影响及机制研究

    Institute of Scientific and Technical Information of China (English)

    阳大庆; 石丽萍; 张普山

    2015-01-01

    Objective To evaluate the role of nucleotide‐binding oligomerization domain 2(NOD2) stimulation in innate immuni‐ty against M ycobacterium tuberculosis .Methods Plate counting as used to evaluate the effect of resisting M ycobacterium tubercu‐losis in human alveolar macrophages .Intracellular NOD2 expression were detected by flow cytometry .Quantitative real‐time PCR was performed to determine the NOD2 ,inducible nitric oxide synthase(iNOS) ,and DEF4B mRNA expression levels using the com‐parative threshold cycle method of relative quantitation .Reactive oxygen species(ROS) were detected by the DFCH probe .Results NOD2 stimulation enhanced the control of intracellular mycobacterial growth in human alveolar macrophages .Although ROS con‐centration did not changed ,the secretion of Nitro Oxygen and the expression of cathelicidin DEFB4 were significantly increased fol‐lowing NOD2 stimulation in human alveolar macrophages .Conclusion NOD2 stimulation may be involved in the early innate con‐trol of Mycobacterium tuberculosis primary infections inducing the generation of Nitro Oxygen and the peptides cathelicidin DEFB4 .%目的:研究核苷酸结合寡聚化结构域2(NOD2)信号在天然抗结核免疫中的作用。方法平板计数法评价NOD2信号对人肺泡巨噬细胞杀结核分枝杆菌效应的影响;流式细胞术和聚合酶链反应(PCR)检测NOD2的表达;实时荧光定量PCR检测一氧化氮合成酶(iNOS)和DEF4B mRNA的表达水平;还原型二氯荧光素(DFCH)探针法测定活性氧(ROS)水平。结果NOD2信号增强了人肺泡巨噬细胞对结核分枝杆菌 H37RV的杀灭。NOD2信号刺激后,人肺泡巨噬细胞中一氧化氮(NO )的分泌和DEF4B的表达均有所增加,但ROS水平变化不明显。结论 NOD2可能通过诱导NO和抗菌肽DEF4B的产生参与了早期的抗结核感染免疫。

  18. Pulmonary alveolar proteinosis and superinfection with pulmonary tuberculosis in a case

    OpenAIRE

    Tekgül, Serpil; Bilaceroglu, Semra; Ozkaya, Sevket; Coskun, Ayse; Komurcuoglu, Berna; Cirak, Ali Kadri

    2011-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare and diffuse lung process, characterized by the presence of alveolar spaces filled with amorphous eosinophilic material. Impaired macrophage function and impaired host defence due to abnormalities of surfactant proteins may favor the growth of microorganisms. The association of alveolar proteinosis with mycobacterial infections is rarely reported. The PAP and superinfection with pulmonary tuberculosis is defined by radiologic and histopathologic i...

  19. Therapeutic Whole-Lung Lavage for Pulmonary Alveolar Proteinosis: A Procedural Update.

    Science.gov (United States)

    Abdelmalak, Basem B; Khanna, Ashish K; Culver, Daniel A; Popovich, Marc J

    2015-07-01

    Pulmonary alveolar proteinosis is a disease caused by increased accumulation and impaired clearance of surfactant by alveolar macrophages. This narrative review summarizes the role of therapeutic whole-lung lavage in the management of pulmonary alveolar proteinosis. We describe the preprocedural evaluation, indications, and anesthetic considerations, along with step-by step technical aspects of the procedure, postoperative recovery, potential complications, and long-term outcomes. PMID:26165897

  20. Effects of ischemia on lung macrophages.

    Directory of Open Access Journals (Sweden)

    Aigul Moldobaeva

    Full Text Available Angiogenesis after pulmonary ischemia is initiated by reactive O(2 species and is dependent on CXC chemokine growth factors, and its magnitude is correlated with the number of lavaged macrophages. After complete obstruction of the left pulmonary artery in mice, the left lung is isolated from the peripheral circulation until 5-7 days later, when a new systemic vasculature invades the lung parenchyma. Consequently, this model offers a unique opportunity to study the differentiation and/or proliferation of monocyte-derived cells within the lung. In this study, we questioned whether macrophage subpopulations were differentially expressed and which subset contributed to growth factor release. We characterized the change in number of all macrophages (MHCII(int, CD11C+, alveolar macrophages (MHCII(int, CD11C+, CD11B- and mature lung macrophages (MHCII(int, CD11C+, CD11B+ in left lungs from mice immediately (0 h or 24 h after left pulmonary artery ligation (LPAL. In left lung homogenates, only lung macrophages increased 24 h after LPAL (vs. 0 h; p<0.05. No changes in proliferation were seen in any subset by PCNA expression (0 h vs. 24 h lungs. When the number of monocytic cells was reduced with clodronate liposomes, systemic blood flow to the left lung 14 days after LPAL decreased by 42% (p<0.01 compared to vehicle controls. Furthermore, when alveolar macrophages and lung macrophages were sorted and studied in vitro, only lung macrophages secreted the chemokine MIP-2α (ELISA. These data suggest that ischemic stress within the lung contributes to the differentiation of immature monocytes to lung macrophages within the first 24 h after LPAL. Lung macrophages but not alveolar macrophages increase and secrete the proangiogenic chemokine MIP-2α. Overall, an increase in the number of lung macrophages appears to be critical for neovascularization in the lung, since clodronate treatment decreased their number and attenuated functional angiogenesis.

  1. Secondary pulmonary alveolar proteinosis in hematologic malignancies.

    Science.gov (United States)

    Chaulagain, Chakra P; Pilichowska, Monika; Brinckerhoff, Laurence; Tabba, Maher; Erban, John K

    2014-12-01

    Pulmonary alveolar proteinosis (PAP), characterized by deposition of intra-alveolar PAS positive protein and lipid rich material, is a rare cause of progressive respiratory failure first described by Rosen et al. in 1958. The intra-alveolar lipoproteinaceous material was subsequently proven to have been derived from pulmonary surfactant in 1980 by Singh et al. Levinson et al. also reported in 1958 the case of 19-year-old female with panmyelosis afflicted with a diffuse pulmonary disease characterized by filling of the alveoli with amorphous material described as "intra-alveolar coagulum". This is probably the first reported case of PAP in relation to hematologic malignancy. Much progress has been made on PAP first described by Rosen which is currently classified as idiopathic or primary or autoimmune PAP. Idiopathic PAP occurs as a result of auto-antibodies directed against granulocyte-macrophage colony stimulating factor (GM-CSF) impeding the surfactant clearing function of alveolar macrophages leading to progressive respiratory failure. Whole lung lavage and GM-CSF therapy has improved outcomes in patients with idiopathic PAP. Despite major advancement in the management of hematologic malignancy and its complications, little is known about the type of PAP first described by Levinson and now known as secondary PAP; a term also used when PAP occurs due to other causes such as occupational dusts. In this article we review and analyze the limited literature available in secondary PAP due to hematologic malignancies and present a case of PAP associated with chronic lymphocytic leukemia successfully treated with bendamustine and rituximab. PMID:25300566

  2. Pulmonary alveolar proteinosis

    OpenAIRE

    Patel, Sandeep M; Sekiguchi, Hiroshi; Jordan P Reynolds; Krowka, Michael J.

    2012-01-01

    Pulmonary alveolar proteinosis (PAP) is a disease of alveolar accumulation of phospholipoproteinaceous material that results in gas exchange impairment leading to dyspnea and alveolar infiltrates. There are three forms of PAP: congenital, acquired and idiopathic; of which the latter two are predominant in the adult population. Previous case studies have found that the acquired form can be secondary to various autoimmune, infectious, malignant and environmental etiologies. Recent advances in t...

  3. Pulmonary Alveolar Proteinosis

    OpenAIRE

    Patel, Sandeep M; Hiroshi Sekiguchi; Jordan P Reynolds; Krowka, Michael J.

    2012-01-01

    Pulmonary alveolar proteinosis (PAP) is a disease of alveolar accumulation of phospholipoproteinaceous material that results in gas exchange impairment leading to dyspnea and alveolar infiltrates. There are three forms of PAP: congenital, acquired and idiopathic; of which the latter two are predominant in the adult population. Previous case studies have found that the acquired form can be secondary to various autoimmune, infectious, malignant and environmental etiologies. Recent advances in t...

  4. Primary pulmonary alveolar proteinosis

    OpenAIRE

    Šarac Sanja; Milić Rade; Zolotarevski Lidija; Aćimović Slobodan; Tomić Ilija; Plavec Goran

    2012-01-01

    Introduction. Pulmonary alveolar proteinosis is an uncommon disease characterized by the accumulation of surfactant proteins and phospholipids within the alveolar spaces. Acquired disease can be idiopathic (primary) and secondary. The prevalence of acquired pulmonary alveolar proteinosis is about 0.37 per 100,000 persons. Common symptoms are dyspnea and cough. Chest X-ray shows bilateral perihilar infiltrates. Open-lung biopsy is the gold standard for the diagnosis. Treatment includes w...

  5. Extensive pulmonary alveolar microlithiasis

    OpenAIRE

    Rittayamai, Nuttapol; Muangman, Nisa; Ruangchira-Urai, Ruchira

    2013-01-01

    Pulmonary alveolar microlithiasis is a rare pulmonary disorder that is caused by abnormal sodium-dependent phosphate co-transporter from the mutation of SLC34A2 gene, leading to accumulation of microliths in the alveoli. We report the extensive pulmonary alveolar microlithiasis in an elderly woman who presented with progressive dyspnea for 2 months. Chest radiograph revealed diffuse pulmonary calcification. Tissue histopathology from open lung biopsy demonstrated widespread intra-alveolar lam...

  6. Macrophage-Derived Biomarkers of Idiopathic Pulmonary Fibrosis

    OpenAIRE

    P. Rottoli; Muller-Quernheim, J.; C. Olivieri; Bargagli, E.; Prasse, A.

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a severe, rapidly progressive diffuse lung disease. Several pathogenetic mechanisms have been hypothesized on the basis of the fibrotic lung damage occurring in this disease, and a potential profibrotic role of activated alveolar macrophages and their mediators in the pathogenesis of IPF was recently documented. This paper focuses on recent literature on potential biomarkers of IPF derived from activated alveolar macrophages. Biomarker discovery and clin...

  7. Anti-GM-CSF antibodies in paediatric pulmonary alveolar proteinosis

    OpenAIRE

    Latzin, P; Tredano, M.; Wust, Y; J. de Blic; Nicolai, T; Bewig, B; Stanzel, F.; Kohler, D.; Bahuau, M.; Griese, M

    2005-01-01

    Background: Auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) may be central to the pathogenesis of adult sporadic pulmonary alveolar proteinosis (PAP). The role of anti-GM-CSF auto-antibodies in paediatric forms of PAP is as yet unclear.

  8. Effects of immunosuppressive agent on mRNA expression of anti-aspergillus infection-associated receptors on alveolar macrophage%免疫抑制剂对小鼠肺泡巨噬细胞抗曲霉感染相关受体mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    荣令; 周新; 何牡丹; 李峰

    2009-01-01

    目的 探讨免疫抑制剂对小鼠肺泡巨噬细胞抗曲霉感染相关受体mRNA表达的影响.方法 30只昆明小鼠随机分为2组:正常对照组(6只)和免疫抑制组(24只,环磷酰胺150 mg/kg腹腔注射).免疫抑制组小鼠注射环磷酰胺后4 h、8 h、16 h及24 h,分别随机取6只进行支气管肺泡灌洗,收集肺泡巨噬细胞.正常对照组小鼠注射生理盐水24 h后处死,收集肺泡巨噬细胞.使用逆转录-聚合酶链反应检测小鼠肺泡巨噬细胞Toll样受体2(TLR2)、TLR4、树突状细胞相关C型凝集素1(Dectine-1)mRNA表达变化.结果 与正常对照组比较,腹腔注射环磷酰胺4 h后,TLR2 mRNA表达即出现显著下降(P<0.01);在腹腔注射环磷酰胺8 h后TLR4 mRNA表达出现显著下降(P<0.01);Dectine-1 mRNA在腹腔注射环磷酰胺后无明显变化.结论 免疫抑制剂环磷酰胺能够下调肺泡巨噬细胞抗曲霉感染相关受体TRL2和TLR4 mRNA的表达,对Dectine-1 mRNA的表达未见明显影响.%Objective To investigate the effects of immunosuppressive agent on mRNA expression of anti-aspergillus infection-associated receptors on alveolar macrophage.Methods Thirty Kunming mice were randomly divided into two groups:normal control group(n=6)and immunocompromise group(150 mg/kg cyclophosphamide,intraperitoneal injection,n=24).Six mice were randomly taken to collect alveolar macrophage by bronchoalveolar lavage from immunocompromise group at time of 4,8,12 and 24 hours after immunosuppression.Mice in normal control group were sacrificed to collect alveolar macrophage after receiving normal saline intraperitoneal injection.Reverse transcription-polymerase chain reaction was used for determining the mRNA expression of Toll-like receptor 2(TLR2),TLR4 and dendritic cell-associated C-type lectin 1(Dectine-1).Results TLR2 mRNA expression decreased signiffieantly four hours after cyclophosphamide intraperitoneal injection,and decreased continually to 24 hours(all P<0.01).The

  9. Pulmonary alveolar microlithiasis

    OpenAIRE

    Gayathri Devi, H.J.; K N Mohan Rao; Prathima, K. M.; Das, Jayanth K.

    2011-01-01

    Pulmonary alveolar microlithiasis is a rare disease of unknown cause. We report a case in a young boy who presented with history of failure to thrive and chest X-ray finding suggestive of miliary mottling. Open lung biopsy revealed pulmonary alveolar microlithiasis.

  10. Elevated bronchoalveolar concentrations of MCP-1 in patients with pulmonary alveolar proteinosis.

    Science.gov (United States)

    Iyonaga, K; Suga, M; Yamamoto, T; Ichiyasu, H; Miyakawa, H; Ando, M

    1999-08-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown aetiology characterized by accumulations of lipoproteinaceous material within the alveoli. The alveolar macrophages become increasingly foamy, and are thought to have a role in the pathogenesis of PAP. However, the mechanisms of macrophage recruitment are unclear. In the bronchoalveolar lavage fluid (BALF) of four patients with PAP and 20 normal control subjects, the following were examined: the monocyte chemotactic activity due to the chemokine monocyte chemoattractant protein (MCP)-1 with the use of a chemotactic chamber assay, the levels of MCP-1 by enzyme-linked immunosorbent assay, and the MCP-1 expression on lavage cells by immunocytochemistry and in situ hybridization. The monocyte chemotactic activity in the BALF of the PAP patients was markedly elevated, and the activity was completely absorbed by treatment with anti-MCP-1. The MCP-1 levels in the BALF were surprisingly high in the PAP group (25,100+/-472 pg x mL(-1)), whereas low levels of MCP-1 were detected in the normal control subjects (mean: never smokers 4.8; smokers 10.4 pg x mL(-1)). MCP-1 protein and messenger ribonucleic acid were expressed by macrophages from the PAP patients, and the expression was reduced according to foaming of the cells; there were monocyte-like macrophages with strong expression, small foamy cells with moderate expression, large foamy cells with a faint expression of MCP-1, and ghost cells with no expression. However, the increase of macrophage number in the PAP BALF was relatively small. These data suggest that monocyte chemoattractant protein(-1) expression by alveolar macrophages represents an amplification mechanism for the recruitment of additional macrophages to the alveoli in pulmonary alveolar proteinosis. It is possible that an ingestion of an excess of alveolar materials in pulmonary alveolar proteinosis may impair the macrophage function and the survival, resulting in the lack of a prominent

  11. Alveolar proteinosis in Behçet's disease

    Directory of Open Access Journals (Sweden)

    Tetikkurt Cuneyt

    2010-08-01

    Full Text Available Abstract A 51-year-old man with Behçet's disease complained of fever, dry cough and dyspnea during exertion. Chest CT showed ground glass opacities with interstitial septal thickening in both lungs. Bronchoalveolar lavage (BAL revealed amorphous and lipoproteinaceous material that was periodic acid-Schiff (PAS stain positive. Transbronchial biopsy specimen demonstrated PAS positive alveolar eosinophilic material consistent with pulmonary alveolar proteinosis. Serum anti-granulocyte-macrophage colony stimulating factor (GM-CSF antibody was negative. Recent studies have reported anti-GMCSF not present in the the serum of patients with secondary pulmonary alveolar proteinosis (PAP but they have not reported so in patients with idiopathic PAP. We report a case of alveolar proteinosis in the setting of Behçet's disease with spontaneous remission.

  12. Treatment of Adult Primary Alveolar Proteinosis.

    Science.gov (United States)

    Rodríguez Portal, José Antonio

    2015-07-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant-like lipoproteinaceous material in the distal air spaces and terminal bronchi, which may lead to impaired gas exchange. This accumulation of surfactant is due to decreased clearance by the alveolar macrophages. Its primary, most common form, is currently considered an autoimmune disease. Better knowledge of the causes of PAP have led to the emergence of alternatives to whole lung lavage, although this is still considered the treatment of choice. Most studies are case series, often with limited patient numbers, so the level of evidence is low. Since the severity of presentation and clinical course are variable, not all patients will require treatment. Due to the low level of evidence, some objective criteria based on expert opinion have been arbitrarily proposed in an attempt to define in which patients it is best to initiate treatment. PMID:25896950

  13. Effects of Panax Notoginseng Saponins on Expression of TNF-α mRNA in Alveolar Macrophage of Rabbits with Sea Water Drowning%三七总皂苷对海水淹溺兔肺泡巨噬细胞TNF-αmRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    顾兴; 金发光; 刘同刚

    2011-01-01

    目的 观察海水淹溺后家兔肺组织光镜下变化,并探讨三七总皂苷干预对海水淹溺后家兔肺泡巨噬细胞内TNF-α mRNA表达的影响.方法采用气管切开插入塑料导管、向气管内灌海水4mL/kg,双肺自主通气的方法模拟海水淹溺造成急性肺损伤模型,随机分为对照组、海水淹溺组、三七总皂苷治疗组.于淹溺后进行血气分析,采集支气管肺泡灌洗液,分离和培养肺泡巨噬细胞,并采集肺组织进行病理学分析,逆转录-聚合酶链反应(RT-PCR)检测肺泡巨噬细胞中TNF-α mRNA的表达.结果光镜下,海水淹溺兔肺组织炎症细胞大量浸润,经三七总皂苷治疗后肺组织损伤程度减轻.RT-PCR分析示淹溺后TNF-α mRNA表达显著增高,90min后达最高峰,而三七总皂苷可使之降低.结论海水淹溺急性肺损伤可能与肺泡巨噬细胞内TNF-αmRNA高表达有关.三七总皂苷可降低TNF-α mRNA的高表达,减轻肺损伤程度.%Objective :To observe the histopathology changes of rabbits drowned by sea water and to explore the effect of panax notoginseng saponins on TNF-a mRNA expression. Methods:The drowning model was established with inserting plastic tube to the trachea of rabbits and sea water(4ml7 kg) was poured into air tube with the both of lung auto ventilated to simulate the process of drowning. Rabbits were randomly divided into the control group, the drowning group and the panax notoginseng saponins group. Then the expression of TNF-α mRNA in the alveolar macrophage of rabbits was determined by reverse-transcription polymerase chain reaction (RT-PCR) after drawing. The infiltration of PMN was examined by histopathologic,while the blood gas analysis was determinated. Results: After drowning,the infiltration of PMN and the expression of TNF -α mRNA were significantly increased. However,Panax notoginseng saponins could inhibit the expression in TG and extenuate the degree of acute lung injury. Conclusion:For sea

  14. Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRα gene in the X chromosome pseudoautosomal region 1

    OpenAIRE

    Martinez-Moczygemba, Margarita; Doan, Minh L.; Elidemir, Okan; Fan, Leland L.; Cheung, Sau Wai; Lei, Jonathan T.; Moore, James P.; Tavana, Ghamartaj; Lewis, Lora R; Zhu, Yiming; Muzny, Donna M.; Gibbs, Richard A; Huston, David P.

    2008-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is...

  15. Congenital Pulmonary Alveolar Proteinosis

    OpenAIRE

    Saber Hammami; Khaled Harrathi; Khaled Lajmi; Samir Hadded; Chebil Ben Meriem; Mohamed Néji Guédiche

    2013-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by pulmonary surfactant accumulation within the alveolar spaces. It occurs with a reported prevalence of 0.1 per 100,000 individuals. Two clinically different pediatric types have been defined as congenital PAP which is fatal and a late-onset PAP which is similar to the adult form and less severe. The clinical course of PAP is variable, ranging from spontaneous remission to respiratory failure. Whole-lung lavage is the curr...

  16. 糖尿病大鼠肺泡巨噬细胞TLR4的表达及对LPS反应性的研究%Expression of Toll-like receptor 4 in alveolar macrophages of diabetic rats and response to LPS

    Institute of Scientific and Technical Information of China (English)

    张放; 李铁英; 康健

    2009-01-01

    Objective To investigate the altered expression of TLR4 in alveolar macrophages of diabetic rats after lipopolysaccharide (LPS) stimulation and the effect of these changes on defending the infection. Methods Thirty-two male Wistar rats were divided into 4 groups, group A: the control group; group B: the diabetic group; group C: the LPS stimulated group; and group D: the diabetic group with LPS stimulation. TLR4 in alveolar macrophages were measured by immunocytochemistry, RT-PCR and Western blot analysis. Results The expressions of TLR4 in group B and group C were higher than that in group A (P < 0. 001). The expression of TLR4 in group D was obviously higher than that of group B and group C (P < 0.001). Conclusion The expression of TLR4 of diabetic rats was higher than that of normal rats and became more higher after LPS stimulation, which is indicated that diabetic bodies were in the proinflammatory state, the mechanism remains to be explored in detail.%目的 观察糖尿病大鼠肺泡巨噬细胞Toll样受体4(TLR4)的表达水平及其对脂多糖(LPS)反应性的变化,探讨该变化在糖尿病机体防御病原体感染中的作用.方法 将32只Wistar雄性大鼠用随机数字表法分为正常组(A组)、糖尿病组(B组)、正常+LPS组(C组)及糖尿病+LPS组(D组).用免疫细胞化学染色法、RT-PCR及Western blot方法检测各组大鼠肺泡巨噬细胞TLR4表达的变化.结果 B组及C组大鼠肺泡巨噬细胞TLR4表达与A组相比均明显增高(P<0.001);D组大鼠肺泡巨噬细胞TLR4表达较B组及C组升高更为明显(P<0.001).结论 与正常大鼠相比,糖尿病大鼠肺泡巨噬细胞TLR4表达明显增高,LPS刺激后其增高更加显著,提示糖尿病机体处于促炎症状态,相关的机制尚有待深入的研究.

  17. Experimental radiation pneumonitis: changes in physiology of the alveolar surface

    International Nuclear Information System (INIS)

    Mice received 2400 rads in two fractions to the thorax; 4 months later at a time when deaths began, mechanical and biochemical properties of the lungs were studied and compared to those of littermate controls. The principal mechanical change was a large increase in the elastance of the alveolar surface element and abnormal surface tension properties of the AF. Alveolar fluid phospholipid content and saturation were only minimally changed; however the alveolar fluid contained a large excess of protein, possible of circulatory origin. The latter may explain the fall in compliance of the alveolar surface and hence of the lung in radiation pneumoritis. A small increase in elastance of the lung tissue element was also found; this correlated with a decrease in lung volume and a small increase in lung hydroxyproline content. These changes may signify the early development of radiation fibrosis. Other features of this model are the frequent occurrence of pleural effusions and the presence of increased numbers of alveolar macrophages in the alveolar lavage

  18. Pulmonary alveolar proteinosis: time to shift?

    Science.gov (United States)

    Papiris, Spyros A; Tsirigotis, Panagiotis; Kolilekas, Likurgos; Papadaki, Georgia; Papaioannou, Andriana I; Triantafillidou, Christina; Papaporfyriou, Anastasia; Karakatsani, Anna; Kagouridis, Konstantinos; Griese, Matthias; Manali, Effrosyni D

    2015-06-01

    Pulmonary alveolar proteinosis (PAP) is categorized into hereditary, secondary and autoimmune PAP (aPAP) types. The common pathogenesis is the ability of the alveolar macrophages to catabolize phagocytized surfactant is affected. Hereditary PAP is caused by mutations involving the GM-CSF signaling, particularly in genes for the GM-CSF receptor and sometimes by GATA2 mutations. Secondary PAP occurs in hematologic malignancies, other hematologic disorders, miscellaneous malignancies, fume and dust inhalation, drugs, autoimmune disorders and immunodeficiencies. aPAP is related to the production of GM-CSF autoantibodies. PAP is characterized morphologically by the inappropriate and progressive 'occupation' of the alveolar spaces by an excessive amount of unprocessed surfactant, limiting gas exchange and gradually exhausting the respiratory reserve. Myeloid cells' immunity deteriorates, increasing the risk of infections. Treatment of PAP is based on its etiology. In aPAP, recent therapeutic advances might shift the treatment option from the whole lung lavage procedure under general anesthesia to the inhalation of GM-CSF 'as needed'. PMID:25864717

  19. Diffuse alveolar hemorrhages

    International Nuclear Information System (INIS)

    The Diffuse Alveolar Hemorrhage (DAH) it is a clinical syndrome that generally manifests with hemoptysis, anemia and infiltrated in the thorax x-ray. From the anatomical point of view, the DAH is defined as the presence of blood in the distal alveolar spaces without it can identify any endobronchial abnormality. The radiological presentation of the DAH is characterized by the presence of having infiltrated of alveolar occupation in the Rx of thorax of prevalence perihiliar and bilateral that goes converging to configure an image of complete consolidation of the air space, the apexes and the periphery of the lungs are generally respected. These infiltrated are solved in one to two weeks, but with the repeated episodes of having bled it can develop interstitial fibrosis

  20. Congenital Pulmonary Alveolar Proteinosis

    Directory of Open Access Journals (Sweden)

    Saber Hammami

    2013-01-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a rare syndrome characterized by pulmonary surfactant accumulation within the alveolar spaces. It occurs with a reported prevalence of 0.1 per 100,000 individuals. Two clinically different pediatric types have been defined as congenital PAP which is fatal and a late-onset PAP which is similar to the adult form and less severe. The clinical course of PAP is variable, ranging from spontaneous remission to respiratory failure. Whole-lung lavage is the current standard treatment for PAP patients. We report a new congenital case of PAP.

  1. Rare Presentation of Pulmonary Alveolar Proteinosis Causing Acute Respiratory Failure

    Directory of Open Access Journals (Sweden)

    Ryan R. Kroll

    2016-01-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a rare condition characterized by dysfunctional alveolar macrophages, which ineffectively clear surfactant and typically cause mild hypoxemia. Characteristic Computed Tomography findings are septal reticulations superimposed on ground-glass opacities in a crazy paving pattern, with a clear juxtaposition between affected and unaffected parenchyma. While traditionally PAP was diagnosed via biopsy, bronchoalveolar lavage (BAL is usually sufficient; the fluid appears milky, and on microscopic examination there are foamy macrophages with eosinophilic granules and extracellular hyaline material that is Periodic Acid-Schiff positive. Standard therapy is whole lung lavage (WLL, although novel treatments are under development. The case presented is a 55-year-old woman with six months of progressive dyspnea, who developed hypoxemic respiratory failure requiring mechanical ventilation; she had typical findings of PAP on imaging and BAL. WLL was ultimately successful in restoring adequate oxygenation. Respiratory failure of this magnitude is a rare finding in PAP.

  2. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis

    OpenAIRE

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y.; Fong, Guo-Hua; Sakmar, Thomas P.; Rafii, Shahin; Ding, Bi-Sen

    2016-01-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the...

  3. Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis

    OpenAIRE

    Piccoli, Luca; Campo, Ilaria; Fregni, Chiara Silacci; Rodriguez, Blanca Maria Fernandez; Minola, Andrea; Sallusto, Federica; Luisetti, Maurizio; Corti, Davide; Lanzavecchia, Antonio

    2015-01-01

    Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in ...

  4. Phagocytic properties of lung alveolar wall cells

    Directory of Open Access Journals (Sweden)

    Tanaka,Akisuke

    1974-04-01

    Full Text Available For the purpose to define the mechanism of heavy metal intoxication by inhalation, morphologic observations were made on rat lungs after nasal instillation of iron colloid particles of positive and negative electric charges. Histochemical observation was also made on the liver and spleen of these animals. The instilled iron colloid particles reach the alveolar cavity easily, as can be seen in the tissue sections stained by Prussian blue reaction. Alveolar macrophages do take up them avidly both of positive and negative charges, though much less the positive particles than negative ones. In contrast, the alveolar epithelial cells take up solely positive particles by phagocytosis but not negative ones. Electron microscope observation revealed that the positive particles are ingested by Type I epithelial cells by pinocytosis and by Type II cells by phagocytosis as well. Then the iron colloid particles are transferred into the basement membrane by exocytosis. Travelling through the basement membrane they are again taken up by capillary endothelial cells by phagocytosis. Some particles were found in the intercellular clefts of capillary endothelial cells but not any iron colloid particles in the intercellular spaces of epithelial cells and in the capillary lumen. However, the liver and spleen tissues of the animals given iron colloid showed a strong positive iron reaction. On the basis of these observations, the mechanism of acute intoxication by inhaling heavy metal dusts like lead fume is discussed from the view point of selective uptake of alveolar epithelial and capillary endothelial cells for the particles of the positive electric cha'rge.

  5. Endogenous lipoid pneumonia preceding diagnosis of pulmonary alveolar proteinosis.

    Science.gov (United States)

    Antoon, James W; Hernandez, Michelle L; Roehrs, Phillip A; Noah, Terry L; Leigh, Margaret W; Byerley, Julie S

    2016-03-01

    Pulmonary alveolar proteinosis (PAP) is an under-reported and under-diagnosed condition, with a high percentage of cases found on autopsy or late stage disease. The etiology of PAP includes genetic, primary (anti-granulocyte-macrophage colony-stimulating factor antibodies) and secondary (oncologic, rheumatologic, infectious, chemical and immunologic) causes. Here, we present the first reported pediatric case of endogenous lipoid pneumonia and non-specific interstitial pneumonitis preceding the development of PAP. PMID:25103284

  6. Pulmonary alveolar proteinosis

    OpenAIRE

    Chan, Adrian Kwok Wai; Takano, Angela; Hsu, Ann Ling; Low, Su Ying

    2014-01-01

    We report a 68-year-old female who presented with chronic cough and progressive dyspnoea. Computed tomography of the thorax and subsequent bronchoscopy confirmed the diagnosis of pulmonary alveolar proteinosis (PAP), which was treated with whole lung lavage. This case is reported in view of the low incidence of PAP.

  7. Abnormal pulmonary macrophages in lysinuric protein intolerance. Ultrastructural, morphometric, and x-ray microanalytic study.

    Science.gov (United States)

    Parto, K; Mäki, J; Pelliniemi, L J; Simell, O

    1994-05-01

    Pediatric patients with lysinuric protein intolerance are predisposed to develop alveolar hemorrhage and pulmonary alveolar proteinosis. We evaluated the ultrastructural features of pulmonary alveolar proteinosis and the potential abnormality of pulmonary macrophages in lysinuric protein intolerance. Lung tissue specimens obtained at autopsy were examined by transmission electron microscopy. Pulmonary macrophages from bronchoalveolar lavages were studied by electron microscopy, morphometry, and x-ray microanalysis and compared with control cells. The macrophages of patients with lysinuric protein intolerance contained significantly more multilamellar structures than did control cells and showed electron-dense material identified to contain excess iron. The predisposition to develop alveolar proteinosis and the abnormal ultrastructure of pulmonary macrophages suggest altered phospholipid metabolism in patients with lysinuric protein intolerance. The marked intramacrophageal accumulations of iron might indicate altered iron metabolism or subclinical hemorrhages in lung tissue. PMID:8192561

  8. Macrophage functions measured by magnetic microparticles in vivo and in vitro

    Science.gov (United States)

    Möller, Winfried; Kreyling, Wolfgang G.; Kohlhäufl, Martin; Häussinger, Karl; Heyder, Joachim

    2001-01-01

    Monodisperse ferrimagnetic iron-oxide particles of 1.4 μm geometric diameter were used to study alveolar macrophage functions (phagocytosis, phagosome transport) and cytoskeletal integrity in healthy subjects and in patients with idiopathic pulmonary fibrosis as well as in cultured macrophages. Dysfunctions in phagocytosis, in phagosome transport and cytoskeletal integrity correlated with an impaired alveolar clearance and could be induced in vitro by cytoskeletal drugs.

  9. Macrophage functions measured by magnetic microparticles in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, Winfried E-mail: moeller@gsf.de; Kreyling, Wolfgang G.; Kohlhaeufl, Martin; Haeussinger, Karl; Heyder, Joachim

    2001-07-01

    Monodisperse ferrimagnetic iron-oxide particles of 1.4 {mu}m geometric diameter were used to study alveolar macrophage functions (phagocytosis, phagosome transport) and cytoskeletal integrity in healthy subjects and in patients with idiopathic pulmonary fibrosis as well as in cultured macrophages. Dysfunctions in phagocytosis, in phagosome transport and cytoskeletal integrity correlated with an impaired alveolar clearance and could be induced in vitro by cytoskeletal drugs.

  10. Macrophage functions measured by magnetic microparticles in vivo and in vitro

    International Nuclear Information System (INIS)

    Monodisperse ferrimagnetic iron-oxide particles of 1.4 μm geometric diameter were used to study alveolar macrophage functions (phagocytosis, phagosome transport) and cytoskeletal integrity in healthy subjects and in patients with idiopathic pulmonary fibrosis as well as in cultured macrophages. Dysfunctions in phagocytosis, in phagosome transport and cytoskeletal integrity correlated with an impaired alveolar clearance and could be induced in vitro by cytoskeletal drugs

  11. Macrophages in vitro as a predictive model in polymer toxicology

    OpenAIRE

    Daly, Paul Michael

    2009-01-01

    Organic polymers S2218600, S2429901 and S2219200 (referred to as Polymer 1, Polymer 2 and Polymer 3, respectively) of varying toxic potential, designed for use in cosmetic aerosols, were used as model substances to predict inflammatory potential. In vivo inflammogenic potential was evaluated by assessment of inflammatory cell profile (alveolar macrophage (AM), polymorphonuclear neutrophil (PMN)) of broncho-alveolar lavage fluid (BAL) 24hrs after a single instillation of either 0.5 mg or 2 mg ...

  12. Pulmonary alveolar proteinosis

    International Nuclear Information System (INIS)

    Since the original description of pulmonary alveolar proteinosis (PAP) as bilaterally symmetric, confluent, perihilar infiltrates, no large series evaluating the relative frequency of radiographic findings has been published. The authors reviewed 53 histologically proved cases and found a predominantly confluent pattern in 77.4%; of these, 61% had a nodular component. A predominantly nodular pattern was seen in 22.6% often with some coalescence or reticular shadows. Distribution was perhilar 56.6%, diffuse in 26.4%, basilar in 26.4%, and asymmetric in 35.8%. The classic pattern was seen in 18.9%. The authors conclude that the spectrum of patterns in pulmonary alveolar proteinosis is wider than generally appreciated

  13. Alveolar Development and Disease

    OpenAIRE

    Jeffrey A Whitsett; Weaver, Timothy E.

    2015-01-01

    Gas exchange after birth is entirely dependent on the remarkable architecture of the alveolus, its formation and function being mediated by the interactions of numerous cell types whose precise positions and activities are controlled by a diversity of signaling and transcriptional networks. In the later stages of gestation, alveolar epithelial cells lining the peripheral lung saccules produce increasing amounts of surfactant lipids and proteins that are secreted into the airspaces at birth. T...

  14. Pulmonary alveolar microlithiasis

    International Nuclear Information System (INIS)

    Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the diffuse and bilateral presence of calcium phosphate microlite in the alveolar spaces. The progression of this potentially lethal disease is show and most of the patients remain asymptomatic during years or decades, resulting in a show deterioration of the pulmonary function. The typical finding of the sand storm in the chest X-ray is characteristic of this entity. Mutations in the SLC34A2 gene that does the coding for the type II co-transporter of sodium phosphate were identified as responsible for this disease. Of the almost 600 cases, only 6 have been reported in Colombia. We are presenting a case of pulmonary alveolar microlite in a 27 year old man, with progressive respiratory distress whose diagnosis was made by the X-ray findings and confirmed by trans bronchial biopsy. In the 2 years follow-up, shows evolution towards deterioration of his respiratory function making him a candidate for lung transplantation.

  15. Alveolar development and disease.

    Science.gov (United States)

    Whitsett, Jeffrey A; Weaver, Timothy E

    2015-07-01

    Gas exchange after birth is entirely dependent on the remarkable architecture of the alveolus, its formation and function being mediated by the interactions of numerous cell types whose precise positions and activities are controlled by a diversity of signaling and transcriptional networks. In the later stages of gestation, alveolar epithelial cells lining the peripheral lung saccules produce increasing amounts of surfactant lipids and proteins that are secreted into the airspaces at birth. The lack of lung maturation and the associated lack of pulmonary surfactant in preterm infants causes respiratory distress syndrome, a common cause of morbidity and mortality associated with premature birth. At the time of birth, surfactant homeostasis begins to be established by balanced processes involved in surfactant production, storage, secretion, recycling, and catabolism. Insights from physiology and engineering made in the 20th century enabled survival of newborn infants requiring mechanical ventilation for the first time. Thereafter, advances in biochemistry, biophysics, and molecular biology led to an understanding of the pulmonary surfactant system that made possible exogenous surfactant replacement for the treatment of preterm infants. Identification of surfactant proteins, cloning of the genes encoding them, and elucidation of their roles in the regulation of surfactant synthesis, structure, and function have provided increasing understanding of alveolar homeostasis in health and disease. This Perspective seeks to consider developmental aspects of the pulmonary surfactant system and its importance in the pathogenesis of acute and chronic lung diseases related to alveolar homeostasis. PMID:25932959

  16. Alveolar development and disease.

    Science.gov (United States)

    Whitsett, Jeffrey A; Weaver, Timothy E

    2015-07-01

    Gas exchange after birth is entirely dependent on the remarkable architecture of the alveolus, its formation and function being mediated by the interactions of numerous cell types whose precise positions and activities are controlled by a diversity of signaling and transcriptional networks. In the later stages of gestation, alveolar epithelial cells lining the peripheral lung saccules produce increasing amounts of surfactant lipids and proteins that are secreted into the airspaces at birth. The lack of lung maturation and the associated lack of pulmonary surfactant in preterm infants causes respiratory distress syndrome, a common cause of morbidity and mortality associated with premature birth. At the time of birth, surfactant homeostasis begins to be established by balanced processes involved in surfactant production, storage, secretion, recycling, and catabolism. Insights from physiology and engineering made in the 20th century enabled survival of newborn infants requiring mechanical ventilation for the first time. Thereafter, advances in biochemistry, biophysics, and molecular biology led to an understanding of the pulmonary surfactant system that made possible exogenous surfactant replacement for the treatment of preterm infants. Identification of surfactant proteins, cloning of the genes encoding them, and elucidation of their roles in the regulation of surfactant synthesis, structure, and function have provided increasing understanding of alveolar homeostasis in health and disease. This Perspective seeks to consider developmental aspects of the pulmonary surfactant system and its importance in the pathogenesis of acute and chronic lung diseases related to alveolar homeostasis.

  17. 骨髓间充质干细胞对脓毒症急性肺损伤大鼠肺泡巨噬细胞NF-κB的调控%Bone marrow mesenchymal stem cells regulate nuclear factor kappaB expression in alveolar macrophages of acute lung injury rats with sepsis

    Institute of Scientific and Technical Information of China (English)

    张继峰; 张紫琦; 雒晓甜; 侯林义; 姜琴; 吕洁萍; 张文凯

    2015-01-01

    BACKGROUND:Bone marrow mesenchymal stem cels have a therapeutic effect on acute lung injury, but the mechanism is unclear. If the mechanism is understood, the majority of patients with acute lung injury can obtain a benefit. OBJECTIVE:To explore the possible mechanism underlying bone marrow mesenchymal stem cels in the treatment of acute lung injury with sepsis in rats. METHODS: (1) Thirty-six adult Wistar rats were randomly divided into three groups, sham operation group (sham group), sepsis group and bone marrow mesenchymal stem cels group (cel treatment group). In the sepsis and cel treatment groups, animal models of sepsis with acute lung injury were established by cecal ligation and puncture, while in the sham group, the cecum was not ligated and punctured. Then, 1 mL normal saline was injected via the femoral vein in the sepsis and sham groups, and 1 mL bone marrow mesenchymal stem cel suspension (1×109/L) was injected into the cel treatment group. After 6 hours, interleukin 10 and macrophage inflammatory protein-2 levels in serum were measured in the three groups. Lung tissues were taken for pathological observation using hematoxylin-eosin staining. (2) Rat alveolar macrophages were obtained by bronchoalveolar lavage, seeded into 24-wel culture plates, and divided into three groups: control group (group A), sepsis model group (group B) and intervention group of bone marrow mesenchymal stem cels (group C). Normal saline, septic plasma, and co-intervention of septic plasma and mesenchymal stem cels were used in the groups A, B, C, respectively. Then, cels in the three groups were cultured in a 5% CO2 incubator at 37℃ for 1 hour. After that, alveolar macrophages were taken to detect whether nuclear factor-κB (P65) protein entered into the nucleus using laser scanning confocal microscopy. RESULTS AND CONCLUSION: (1) The results of animal experiments showed that compared with the sham group, the macrophage inflammatory protein-2 levels in the sepsis group and

  18. The heterogeneity of lung macrophages in the susceptibility to disease

    Directory of Open Access Journals (Sweden)

    Luisa Morales-Nebreda

    2015-09-01

    Full Text Available Alveolar macrophages are specialised resident phagocytes in the alveolus, constituting the first line of immune cellular defence in the lung. As the lung microenvironment is challenged and remodelled by inhaled pathogens and air particles, so is the alveolar macrophage pool altered by signals that maintain and/or replace its composition. The signals that induce the recruitment of circulating monocytes to the injured lung, as well as their distinct gene expression profile and susceptibility to epigenetic reprogramming by the local environment remain unclear. In this review, we summarise the unique characteristics of the alveolar macrophage pool ontogeny, phenotypic heterogeneity and plasticity during homeostasis, tissue injury and normal ageing. We also discuss new evidence arising from recent studies where investigators described how the epigenetic landscape drives the specific gene expression profile of alveolar macrophages. Altogether, new analysis of macrophages by means of “omic” technologies will allow us to identify key pathways by which these cells contribute to the development and resolution of lung disease in both mice and humans.

  19. Theoretical basis of alveolar sampling.

    OpenAIRE

    Kelman, G R

    1982-01-01

    The conditions under which the partial pressure of a solvent in the alveolar gas is likely to provide a valid index of its partial pressure in the mixed venous blood, and thus of whole-body exposure, is explored on a theoretical basis. Under steady-state conditions, providing the solvent's blood/gas partition coefficient exceeds 10, its mixed venous and alveolar pressures will agree within 10% and become virtually identical during the prolonged expiration necessary to obtain an alveolar sampl...

  20. Pulmonary alveolar proteinosis: diagnostic and therapeutic challenges

    Directory of Open Access Journals (Sweden)

    Campo Ilaria

    2012-06-01

    Full Text Available Abstract Pulmonary Alveolar Proteinosis (PAP is a rare syndrome characterized by pulmonary surfactant accumulation within the alveolar spaces. It occurs with a reported prevalence of 0.1 per 100,000 individuals and in distinct clinical forms: autoimmune (previously referred to as the idiopathic form, represents the vast majority of PAP cases, and is associated with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF auto-antibodies; GMAbs, secondary (is a consequence of underlying disorders, congenital (caused by mutations in the genes encoding for the GM-CSF receptor, and PAP-like syndromes (disorders associated with surfactant gene mutations. The clinical course of PAP is variable, ranging from spontaneous remission to respiratory failure. Whole lung lavage (WLL is the current standard treatment for PAP patients and although it is effective in the majority of cases, disease persistence is not an unusual outcome, even if disease is well controlled by WLL. In this paper we review the therapeutic strategies which have been proposed for the treatment of PAP patients and the progress which has been made in the understanding of the disease pathogenesis.

  1. Comparison of affinity of mannose receptor of peritoneal macrophage and alveolar macrophage and its ligands in rats%大鼠肺泡、腹腔巨噬细胞甘露糖受体与配体的亲和力比较

    Institute of Scientific and Technical Information of China (English)

    吕正光; 刘莉; 梅其炳; 曹尉; 王志鹏; 刘新友; 余璐

    2005-01-01

    目的:探讨来源于不同组织肺泡、腹腔巨噬细胞甘露糖受体(macrophage mannose receptor, MMR)与配体的亲和力差异.方法:采用支气管肺泡灌洗和腹腔冲洗法获得肺泡和腹腔巨噬细胞(macrophage,Mφ),经纯化、鉴定后与异硫氰酸荧光标记的甘露糖基化牛血清白蛋白(M-FITC-BSA)孵育20 min,分别加入D-甘露糖、D-半乳糖、EDTA,采用荧光显微镜和流式细胞仪检测甘露糖受体(mannose receptor,MR)与配体的结合情况.结果:Mφ上存在MR,MR与配体的结合属于Ca2+依赖性,其结合可被D-甘露糖、EDTA抑制,而不受D-半乳糖的抑制;腹腔MMR与配体的亲和力高于肺泡MMR.结论:腹腔MMR与配体的亲和力高于肺泡MMR.

  2. The Alveolar Epithelium Determines Susceptibility to Lung Fibrosis in Hermansky-Pudlak Syndrome

    OpenAIRE

    Young, Lisa R.; Gulleman, Peter M.; James P Bridges; Weaver, Timothy E.; Deutsch, Gail H.; Blackwell, Timothy S.; McCormack, Francis X.

    2012-01-01

    Rationale: Hermansky-Pudlak syndrome (HPS) is a family of recessive disorders of intracellular trafficking defects that are associated with highly penetrant pulmonary fibrosis. Naturally occurring HPS mice reliably model important features of the human disease, including constitutive alveolar macrophage activation and susceptibility to profibrotic stimuli.

  3. An Open-Label Trial of Rituximab Therapy in Pulmonary Alveolar Proteinosis

    OpenAIRE

    Kavuru, Mani S.; Malur, Anagha; Marshall, Irene; Barbara P. Barna; Meziane, Moulay; Huizar, Isham; Dalrymple, Heidi; Karnekar, Reema; Thomassen, Mary Jane

    2011-01-01

    Rituximab, a monoclonal antibody directed against the B-lymphocyte antigen CD20, has shown promise in several autoimmune disorders. Pulmonary Alveolar Proteinosis (PAP) is an autoimmune disorder characterized by autoantibodies to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF).

  4. Characteristics of a Large Cohort of Patients with Autoimmune Pulmonary Alveolar Proteinosis in Japan

    OpenAIRE

    Inoue, Yoshikazu; Trapnell, Bruce C.; Tazawa, Ryushi; Arai, Toru; Takada, Toshinori; HIZAWA, NOBUYUKI; Kasahara, Yasunori; Tatsumi, Koichiro; Hojo, Masaaki; Ichiwata, Toshio; Tanaka, Naohiko; Yamaguchi, Etsuro; Eda, Ryosuke; Oishi, Kazunori; Tsuchihashi, Yoshiko

    2008-01-01

    Rationale: Acquired pulmonary alveolar proteinosis (PAP) is a syndrome characterized by pulmonary surfactant accumulation occurring in association with granulocyte/macrophage colony-stimulating factor autoantibodies (autoimmune PAP) or as a consequence of another disease (secondary PAP). Because PAP is rare, prior reports were based on limited patient numbers or a synthesis of historical data.

  5. Pulmonary alveolar proteinosis: a complete response to GM-CSF therapy

    OpenAIRE

    Barraclough, R; Gillies, A

    2001-01-01

    Pulmonary alveolar proteinosis is a rare condition traditionally requiring treatment with whole lung lavage. The case is presented of a young man who obtained complete remission following treatment with granulocyte-macrophage colony stimulating factor, a new treatment option.



  6. Diesel and biodiesel exhaust particle effects on rat alveolar machrophages with in vitro exposure

    Science.gov (United States)

    We conducted in vitro exposures of Wistar rat alveolar macrophages (AM) to compare and contrast the toxicity of particulate matter (PM) produced in combustion of biodiesel blend (B20) and petroleum diesel (PDEP). The PM contain detectable levels of transition metals and ions howe...

  7. CT in alveolar proteinosis

    International Nuclear Information System (INIS)

    Nine patients with pulmonary alveolar proteinosis (PAP) were scanned with CT. Results were not specific for PAP but may be help0ful in the differential diagnosis is visualization of pulmonary vessels is maintained and air bronchograms are scarce in diseased areas. CT is better than conventional radiography in identifying infectious complications and evaluating disease extent and may help in deciding whether or not therapeutic lavage is indicated. CT has also identified an interstitial component of PAP that correlates histologically with an inflammatory cell infiltrate. The cellular infiltrate may play a role in the development of the interstitial fibrosis seen in some cases of PAP

  8. Expression and preliminary functional analysis of Siglec-F on mouse macrophages

    Institute of Scientific and Technical Information of China (English)

    Yin-he FENG; Hui MAO

    2012-01-01

    Sialic acid-binding immunoglobulin-like lectin (Siglec)-F is a mouse functional paralog of human Siglec-8 that induces apoptosis in human eosinophils,end therefore may be useful as the basis of treatments for a variety of disorders associated with eosinophil hyperactivity,such as asthma.The expression pattern and functions of this protein in various cell types remain to be elucidated.The aim of this study was to determine the expression of Siglec-F on mouse macrophages by immunocytochemical staining,and also to investigate the effects of Siglec-F engagement by a Siglec-F antibody on phagocytic activity of macrophages.The results showed that Siglec-F expression was detected on mouse alveolar macrophages,but not on peritoneal macrophages.Furthermore,Siglec-F engagement did not affect the phagocytic activity of alveolar macrophages in the resting state or in the activated state following stimulation by the proinflammatory mediator tumor necrosis factor alpha (TNF-α) or lipopolysaccharide (LPS).Siglec-F expression on alveolar macrophages may be a result of adaptation.Macrophages actively regulate immune responses via production of cytokines.Therefore,further investigation of the effects of Siglec-F engagement on immune mediators or cytokines released by alveolar macrophages is required.

  9. Granulocyte-macrophage colony-stimulating factor and pulmonary surfactant homeostasis.

    Science.gov (United States)

    Reed, J A; Whitsett, J A

    1998-01-01

    Pulmonary surfactant lining the alveolus of the lung is critical to postnatal adaptation to air breathing. Precise concentrations of surfactant proteins and lipids are maintained in the alveolar space by a careful balance among synthesis, recycling, and catabolism. Pulmonary alveolar proteinosis is a rare pulmonary disease associated with accumulation of surfactant lipids and proteins in the alveolar spaces. Recent work with transgenic mice demonstrated that disruption of the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) or the common beta-subunit of the GM-CSF receptor caused alveolar proteinosis that was histologically similar to that seen in human patients. The defect in surfactant homeostasis is caused by decreased surfactant clearance, mediated (at least in part) by dysfunction of the alveolar macrophage. Local production of GM-CSF corrects the alveolar proteinosis in the GM-CSF knockout mouse. Likewise, transplantation of wild-type bone marrow cells expressing the common beta-chain of the GM-CSF receptor restores surfactant homeostasis in the GM-CSF receptor knockout mouse. These studies demonstrate the previously unanticipated role of GM-CSF signaling in surfactant homeostasis, mediated (at least in part) by its actions on the clearance of surfactant lipids and proteins by the alveolar macrophage. These findings may have important implications for the diagnosis and treatment of pulmonary alveolar proteinosis syndromes in humans. PMID:9686680

  10. Genetics Home Reference: pulmonary alveolar microlithiasis

    Science.gov (United States)

    ... Genetics Home Health Conditions pulmonary alveolar microlithiasis pulmonary alveolar microlithiasis Enable Javascript to view the expand/collapse boxes. Print All Open All Close All Description ...

  11. Role and mechanism of signal pathway mediated by Toll-like receptor 9-myeloid differentiation factor 88 in alveolar macrophages in ventilator-induced lung injury in rats%肺泡巨噬细胞Toll样受体9-髓样分化因子88信号通路在呼吸机相关性肺损伤中的作用机制研究

    Institute of Scientific and Technical Information of China (English)

    戴惠军; 潘灵辉; 林飞; 葛万运; 李玮; 贺盛

    2014-01-01

    Objective To investigate the role of Toll-like receptor9 (TLR9)-myeloid differentiation factor 88 (MyD88) signal pathway in alveolar macrophages in ventilator-induced lung injury (VILI).Methods 30 adult male Sprague-Dawley (SD) rats were randomly assigned to three groups (with 10 rats in each group).Group A was the control group,with spontaneous respiration after tracheostomy.Rats in group B received mechanical ventilation for 4 hours with normal tidal volume (VT) 7 ml/kg after tracheostomy,and group C rats received mechanical ventilation with VT 40 ml/kg for 4 hours.After termination of ventilation,examination with transmission electron microscopy was performed to observe the ultrastructure changes in alveolar epithelial cell type Ⅱ (AEC Ⅱ) of the lung.Lung wet/dry ratios (W/D) and total protein concentration,the concentration of interleukins (IL-6 and IL-1 β) in bronchoalveolar lavage fluid (BALF) were determined.The protein and mRNA expressions of TLR9,MyD88 and nuclear factor-κB (NF-κB) in alveolar macrophages were assayed by Western Blot and real-time reverse transcription-polymerase chain reaction (RT-PCR).Results The ultrastructure of AEC Ⅱ in the group A and group B was almost normal,whereas the chromatin of the nuclei,the lamellar corpuscles in the cytoplasm,the cell membrane and the microvilli of the AEC Ⅱ in the group C showed injurious changes in various degrees.When the group C was compared with the group A and the group B,it was shown that the W/D ratios (5.54 ± 0.17 vs.4.58 ± 0.17,4.69 ± 0.16) and total protein concentration (g/L:6.33 ± 0.61 vs.0.45 ± 0.05,0.47 ± 0.04),IL-6 (μg/L:1.989 ± 0.103 vs.1.033 ± 0.061,1.010 ± 0.069) and IL-lβ (ng/L:2.79 ±0.25 vs.1.05 ±0.15,1.23 ±0.22) in BALF,the protein expressions of TLR9,MyD88 and NF-κB [TLR9 (A value):0.770 ±0.042 vs.0.300 ±0.027,0.310 ±0.037; MyD88 (A value):0.950 ±0.091 vs.0.560 ±0.082,0.580±0.084; NF-κB(A value):1.020 ±0.076 vs.0.740 ±0.052,0.700 ±0.076] in alveolar

  12. Role of macrophages in the progression of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Sabrina; Gea-Sorlí; Daniel; Closa

    2010-01-01

    In addition to pancreatic cells,other inflammatory cell populations contribute to the generation of inflammatory mediators during acute pancreatitis.In particular,macrophages could be activated by mediators released during pancreatitis by a damaged pancreas.It has been reported that peritoneal macrophages,alveolar macrophages and Kupffer cells become activated in different stages of severe acute pancreatitis.However,macrophages display remarkable plasticity and can change their physiology in response to environmental cues.Depending on their microenvironmental stimulation,macrophages could follow different activation pathways resulting in marked phenotypic heterogeneity.This ability has made these cells interesting therapeutical targets and several approaches have been assayed to modulate the progression of inflammatory response secondary to acute pancreatitis.However,despite the recent advances in the modulation of macrophage function in vivo,the therapeutical applications of these strategies require a better understanding of the regulation of gene expression in these cells.

  13. Pulmonary alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    Hadice Selimoğlu Şen

    2011-06-01

    Full Text Available Pulmonary alveolar proteinosis is a rare disease characterized by the accumulation of lipoproteinosis material within the alveoli. A 36 age male patient applied to our hospital with dyspnea that began 5 months ago. Bilateral diffuse infiltration on postero-anterior chest graphy was seen. Arterial blood gas measurements (ABG was: pH:7.44, pCO2: 36 mmHg, pO2: 49 mmHg, SaO2: 85%, HCO3: 24 mmol/L. High resolution computed tomography (HRCT reported as bilateral diffuse ground glass areas and interlobuler septal thickening on this areas. Asido resistant bacillus was negative in sputum at three times and was also negative in post bronchoscopic sputum and bronchoalveoler lavage material. Wedge resection was made by video-assisted thoracoscopic surgery. Histopathology report of biopsy material revealed “Pulmonary alveolar proteinosis (PAP”. Massive lung lavage under general anesthesia was planned for patient. Clinical improvement was seen in patient beginning from admission and ABG measurements entered the recovery trend in follow-up. Partial pressure of oxygen was increased to 65 mmHg and patient was followed without lung lavage. Control chest radiography and HRCT showed significant radiological improvement. After three months, radiological lesions had completely regressed at control HRCT. As a result, in patients with symptoms and radiologically bilateral diffuse infiltration physicians should consider PAP as a rare disease in the differential diagnosis.

  14. Bulky PAH-DNA induced by exposure of a co-culture model of human alveolar macrophages and embryonic epithelial cells to atmospheric particulate pollution; Adduits encombrants a l'ADN dans des cocultures de cellules pulmonaires humaines exposees a une pollution atmospherique particulaire

    Energy Technology Data Exchange (ETDEWEB)

    Abbas, Imane; Garcon, Guillaume; Billet, Sylvain; Shirali, Pirouz [Universite Lille Nord de France - Lille (France); Unite de Chimie Environnementale et Interactions sur le Vivant, MREI, Universite du Littoral Cote d' Opale, Dunkerque (France); Andre, Veronique; Le Goff, Jeremie; Sichel, Francois [GRECAN, Universite de Caen Basse-Normandie et centre Francois Baclesse, Caen (France); Roy Saint-Georges, Francoise; Mulliez, Philippe [Service de Pneumologie, Hopital Saint-Philibert, GHICL, Lille (France)

    2012-01-15

    Because of their deep penetration in human lungs, fine airborne particulate matter were described as mainly responsible for the deleterious effects of exposure to air pollution on health. Organic constituents are adsorbed on particles surface and, after inhalation, some (polycyclic aromatic hydrocarbons, PAHs) can be activated into reactive metabolites and can bind to DNA. The formation of bulky DNA adducts has been researched after exposure of mono-and co-cultures of alveolar macrophages (AM) and human embryonic human lung epithelial (L132), to fine air pollution particulate matter Air samples have been collected with cascade impactor and characterized: size distribution (92.15% < 2.5{mu}.m), specific surface area (1 m{sup 2}/g), inorganic (Fe, AI, Ca, Na, K, Mg, Pb, etc.) and organic compounds (PAHs, etc.). {sup 32}P post-labeling method was applied to detect bulky DNA adducts in AM and L132, in mono-and co-cultures, 72 h after their exposure to atmospheric particles at their Lethals and Effects concentrations or (LC or CE) to 50% (i.e. MA: EC{sub 50} = 74.63 {mu}g/mL and L132: LC-5-0 = 75.36 {mu}g/mL). Exposure to desorbed particles (MA: C1= 61.11 {mu}g/mL and L132 : C2 = 61.71 {mu}g/mL) and B[a]P (1 {mu}M) were included. Bulky PAH-DNA adducts were detected in AM in mono-culture after exposure to total particles (Pt), to B[a]P and desorbed particles (Pd). Whatever the exposure, no DNA adduct was detected in L132 in mono-culture. These results are coherent with the enzymatic activities of cytochrome P450 l Al in AM and L132. Exposure of co-culture to Pt, or Pd induced bulky adducts to DNA in AM but not in L132. Exposure to B[a]P alone has altered the DNA of AM and L132, in co-culture. Exposure to Pt is closer to the environmental conditions, but conferred an exposure to amounts of genotoxic agents compared to studies using organic extracts. The formation of bulky DNA adducts was nevertheless observed in AM exposed to Pt, in mono- or co-culture, indicating that

  15. The immunomodulatory effect of inhaled granulocyte-macrophage colony-stimulating factor in cystic fibrosis. A new treatment paradigm

    DEFF Research Database (Denmark)

    Heslet, Lars; Bay, Christiane; Nepper-Christensen, Steen

    2012-01-01

    Patients with cystic fibrosis (CF) experience recurrent infections and develop chronically infected lungs, which initiates an altered immunological alveolar environment. End-stage pulmonary dysfunction is a result of a long sequence of complex events in CF, progressing to alveolar macrophage...

  16. Particle-induced indentation of the alveolar epithelium caused by surface tension forces.

    Science.gov (United States)

    Mijailovich, S M; Kojic, M; Tsuda, A

    2010-10-01

    Physical contact between an inhaled particle and alveolar epithelium at the moment of particle deposition must have substantial effects on subsequent cellular functions of neighboring cells, such as alveolar type-I, type-II pneumocytes, alveolar macrophage, as well as afferent sensory nerve cells, extending their dendrites toward the alveolar septal surface. The forces driving this physical insult are born at the surface of the alveolar air-liquid layer. The role of alveolar surfactant submerging a hydrophilic particle has been suggested by Gehr and Schürch's group (e.g., Respir Physiol 80: 17-32, 1990). In this paper, we extended their studies by developing a further comprehensive and mechanistic analysis. The analysis reveals that the mechanics operating in the particle-tissue interaction phenomena can be explained on the basis of a balance between surface tension force and tissue resistance force; the former tend to move a particle toward alveolar epithelial cell surface, the latter to resist the cell deformation. As a result, the submerged particle deforms the tissue and makes a noticeable indentation, which creates unphysiological stress and strain fields in tissue around the particle. This particle-induced microdeformation could likely trigger adverse mechanotransduction and mechanosensing pathways, as well as potentially enhancing particle uptake by the cells. PMID:20634359

  17. Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas

    Directory of Open Access Journals (Sweden)

    Jason M. Fritz

    2014-11-01

    Full Text Available Chronic inflammation is a risk factor for lung cancer, and low dose aspirin intake reduces lung cancer risk. However, the roles that specific inflammatory cells and their products play in lung carcinogenesis have yet to be fully elucidated. In mice, alveolar macrophage numbers increase as lung tumors progress, and pulmonary macrophage programming changes within 2 weeks of carcinogen exposure. To examine how macrophages specifically affect lung tumor progression, they were depleted in mice bearing urethane-induced lung tumors using clodronate-encapsulated liposomes. Alveolar macrophage populations decreased to ≤ 50% of control levels after 4-6 weeks of liposomal clodronate treatment. Tumor burden decreased by 50% compared to vehicle treated mice, and tumor cell proliferation, as measured by Ki67 staining, was also attenuated. Pulmonary fluid levels of IGF-I, CXCL1, IL-6 and CCL2 diminished with clodronate liposome treatment. Tumor associated macrophages expressed markers of both M1 and M2 programming in vehicle and clodronate liposome treated mice. Mice lacking CCR2 (the receptor for macrophage chemotactic factor CCL2 had comparable numbers of alveolar macrophages and showed no difference in tumor growth rates when compared to similarly treated wild-type mice suggesting that while CCL2 may recruit macrophages to lung tumor microenvironments, redundant pathways can compensate when CCL2/CCR2 signaling is inactivated. Depletion of pulmonary macrophages rather than inhibition of their recruitment may be an advantageous strategy for attenuating lung cancer progression.

  18. Elevated monocyte chemotactic proteins 1, 2, and 3 in pulmonary alveolar proteinosis are associated with chemokine receptor suppression.

    Science.gov (United States)

    Bonfield, Tracey L; John, Nejimol; Malur, Anagha; Barna, Barbara P; Culver, Daniel A; Kavuru, Mani S; Thomassen, Mary Jane

    2005-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare autoimmune lung disease characterized by abnormal surfactant accumulation within alveolar macrophages, and circulating auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) resulting in functional GM-CSF deficiency. Monocyte/macrophage chemotactic protein-1 (MCP-1) is elevated in PAP, suggesting association with the pathophysiology. Because PAP has been associated with inflammatory pulmonary changes, we hypothesized that other MCP family chemokines would be present and that Chemokine Chemotaxis Receptor 2 (CCR2) would be elevated on PAP mononuclear cells. Here we show for the first time that MCP-2 and MCP-3, like MCP-1, are highly elevated in PAP. We also confirm that PAP alveolar macrophages and not epithelial cells produce MCP-1, and that MCP-1 from PAP lung has functional chemoattractant activity. Surprisingly, CCR2 expression is diminished in PAP lymphocytes and alveolar macrophages compared to controls. Further, MCP-1 from PAP lung suppresses CCR2 expression in vitro, suggesting that in PAP, MCP-1 participates in an autocrine regulatory network in vivo. PMID:15596412

  19. Pathophysiology Review Series: Alcohol Abuse, the Alveolar Macrophage, and Pneumonia

    OpenAIRE

    Mehta, Ashish J.; Guidot, David M.

    2012-01-01

    Alcohol use, and misuse, has been a part of human culture for thousands of years. In the modern medical era a great deal of attention has been justifiably focused on elucidating the mechanisms underlying the psychological and biological addiction to alcohol. However, a significant percentage, if not the majority, of alcohol-related morbidity and mortality occurs in individuals who do not meet the formal diagnostic criteria for alcohol use disorders. For example, many serious medical consequen...

  20. Abses Alveolar Akut Pada Anak

    OpenAIRE

    Delfitri, Meri

    2008-01-01

    Abses alveolar akut adalah suatu kumpulan nanah yang terlokalisasi dalam tulang alveolar sekitar apeks gigi setelah kematian pulpa yang merupakan kelanjutan proses infeksi yang mulai di pulpa dan berkembang ke jaringan periapikal. Perluasan infeksi dari pulpa non vital dapat melalui foramen apikal menuju jaringan periapikal yang mengakibatkan inflamasi akut, bila disertai dengan meningkatnya virulensi bakteri streptokokus alfa, disertai staffilokokus dan sejumlah anaerob lainnya serta r...

  1. Toxicity of mycotoxins for the rat pulmonary macrophage in vitro

    International Nuclear Information System (INIS)

    The presence of mycotoxins in grains is well documented. Workers in grain handling occupations are commonly exposed to grain dust aerosols. Work in our laboratory has shown that T-2 toxin is highly toxic to rat alveolar macrophages in vitro, causing loss of viability, release of radiolabeled chromium, inhibition of macromolecular synthesis, inhibition of phagocytosis, and inhibition of macrophage activation. Similarly, patulin caused a significant release of radiolabeled chromium, decrease in ATP levels, significant inhibition of protein and RNA synthesis, and inhibition of phagocytosis. The data show that both T-2 toxin and patulin are highly toxic to rat alveolar macrophages in vitro. The data further suggest that the presence of these mycotoxins in airborne respirable dust might present a hazard to exposed workers

  2. Toxicity of mycotoxins for the rat pulmonary macrophage in vitro.

    Science.gov (United States)

    Sorenson, W G; Gerberick, G F; Lewis, D M; Castranova, V

    1986-04-01

    The presence of mycotoxins in grains is well documented. Workers in grain handling occupations are commonly exposed to grain dust aerosols. Work in our laboratory has shown that T-2 toxin is highly toxic to rat alveolar macrophages in vitro, causing loss of viability, release of radiolabeled chromium, inhibition of macromolecular synthesis, inhibition of phagocytosis, and inhibition of macrophage activation. Similarly, patulin caused a significant release of radiolabeled chromium, decrease in ATP levels, significant inhibition of protein and RNA synthesis, and inhibition of phagocytosis. The data show that both T-2 toxin and patulin are highly toxic to rat alveolar macrophages in vitro. The data further suggest that the presence of these mycotoxins in airborne respirable dust might present a hazard to exposed workers. PMID:2423320

  3. Siderocalin inhibits the intracellular replication of Mycobacterium tuberculosis in macrophages

    DEFF Research Database (Denmark)

    Johnson, Erin E; Srikanth, Chittur V; Sandgren, Andreas;

    2010-01-01

    variant form of siderocalin, which is expressed only in the macrophage cytosol, inhibited intracellular M.tb growth as effectively as the normal, secreted form, an observation that provides mechanistic insight into how siderocalin might influence iron acquisition by the bacteria in the phagosome. Our...... siderocalin expression is upregulated following M.tb infection of mouse macrophage cell lines and primary murine alveolar macrophages. Furthermore, siderocalin added exogenously as a recombinant protein or overexpressed in the RAW264.7 macrophage cell line inhibited the intracellular growth of the pathogen. A......Siderocalin is a secreted protein that binds to siderophores to prevent bacterial iron acquisition. While it has been shown to inhibit the growth of Mycobacterium tuberculosis (M.tb) in extracellular cultures, its effect on this pathogen within macrophages is not clear. Here, we show that...

  4. Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation.

    Directory of Open Access Journals (Sweden)

    Mirjam Stahl

    Full Text Available Idiopathic pulmonary fibrosis is characterized by abundant collagen production and accumulation of alternatively activated macrophages (M2 in the lower respiratory tract. Mechanisms as to how alveolar macrophages are activated by collagen breakdown products are unknown. Alveolar macrophages were obtained by bronchoalveolar lavage from 30 patients with idiopathic pulmonary fibrosis (IPF and 37 healthy donors (HD. Alveolar macrophages were cultured in the presence of collagen type I, III, IV and V monomers w/wo a neutralizing antibody against scavenger receptor I class A (CD204. Culture supernatants were assayed for the M2 markers CCL18, CCL2, and interleukin-1 receptor antagonist (IL-1ra by ELISA. Furthermore, expression of phospho-Akt was measured using ELISA and expression of CD204 by RT-PCR and flow cytometry. Stimulation with collagen type I and III monomers significantly up-regulated CCL18, IL-1ra production of alveolar macrophages. Furthermore, expression of CCL2 and CD204 were up-regulated by collagen type I exposure. In addition, collagen type I stimulation increased pospho-Akt expression. Collagen type I effects were abrogated by neutralizing antiCD204 and a non-selective Phosphatidylinositide 3-kinase inhibitor (LY294002. Spontaneous CD204 expression of alveolar macrophages was significantly increased in patients with IPF. In conclusion, our findings demonstrate that monomeric collagen type I via CD204 induces phospho-Akt expression shifting alveolar macrophages to the profibrotic M2 type. Innate immune responses induced by collagen monomers might perpetuate pulmonary fibrosis.

  5. L’onomastique comorienne: etude linguistique

    OpenAIRE

    Yahaya, Moinaecha Cheikh

    2012-01-01

    Dans cette etude nous nous sommes fixé commee objectif principal la recherche des morphèmes nominaux altérés dans la langue courante et qui se manifestent au niveau des noms propres surtout au niveau des composés. Ces éléments nous permettront de mieux comprendre le système morphologique du comorien et compléter une etude en cours sur la morphologie des nominaux. L’étude morphologique du nom propre sera complétée par une étude syntaxique des différents éléments qui le composent. Les indicatio...

  6. Life history of plutonium dioxide in the lung: from macrophage to carcinoma

    International Nuclear Information System (INIS)

    The pulmonary macrophage exerts a large influence upon the distribution of alpha energy from inhaled 239PuO2, while the pulmonary epithelium serves as the prime 'target' cell for neoplastic transformation. In the rat, of the total radiation energy absorbed in the lung, about 80 percent is delivered to the alveolar septae, 19 percent to the vascular tissues and less than 1 percent to the bronchial epithelium. Of the radiation energy delivered to the alveolar septae, about 10 percent is absorbed by alveolar epithelium, 10 percent by macrophage, 10 percent by endothelium and 70 percent by other cellular and noncellular elements. Both the type II alveolar epithelium and the bronchiolar epithelium serve as the probable cells of origin for induced adenocarcinoma

  7. Pulmonary surfactant and macrophages studied at the air/liquid interface revealed by Brewster angle microscopy (BAM)

    Science.gov (United States)

    Telesford, Dana-Marie; Allen, Heather; Carlson, Tracy; Schlesinger, Larry

    2012-04-01

    The alveolus is lined with a complex mixture of lipids and proteins called pulmonary surfactant (PS) that lower surface tension at the alveolar air/liquid interface. The surface area of the lung for a 70 kg adult human at total lung capacity is ˜70 m^2. The large surface area and the direct exposure to the environment with every inhalation make this organ more susceptible to invasion by viruses, bacteria, and small particles. The most abundant cell recovered in human lung lavage is the alveolar macrophage which accounts for 85% of the total. The primary function of the alveolar macrophage is to defend the lung against invasion, but also in the clearance of surfactant components in the lung. Quintero and Wright,^1 in an in vitro study observing alveolar macrophage metabolism of two lipid components dipalmitoyl phosphatidylglycerol (DPPG) and dipalmitoyl phosphatidylcholine (DPPC), noted that DPPG was removed at a faster rate. The mechanism by which this process takes place is not fully understood and our aim is to investigate the interactions of macrophages with different lipids using Brewster angle microscopy. Preliminary studies suggest that THP-1 differentiated macrophages do not significantly perturb DPPC and DPPG monolayers and research utilizing alveolar macrophages is underway. The effect of PS SP-A and SP-D is also discussed.

  8. Displasia alveolar congénita Congenital alveolar dysplasia

    OpenAIRE

    D.P. Sánchez Hernández; M.M. Suárez Galvis; M.T. García Vélez; A. Uribe Molina

    2012-01-01

    La displasia alveolar congénita es una patología congénita poco frecuente caracterizada por disminución de las unidades alveolares y anormalidades del desarrollo de la vasculatura pulmonar. Esta entidad produce hipertensión pulmonar severa e hipoxemia persistente con una evolución mortal en la mayoría de los casos. Afecta generalmente a recién nacidos a término, con un test de Apgar normal, que posteriormente desarrollan dificultad respiratoria, habitualmente en el primer día de vida. La enfe...

  9. M2 polarization enhances silica nanoparticle uptake by macrophages

    Directory of Open Access Journals (Sweden)

    Jessica eHoppstädter

    2015-03-01

    Full Text Available While silica nanoparticles have enabled numerous industrial and medical applications, their toxicological safety requires further evaluation. Macrophages are the major cell population responsible for nanoparticle clearance in vivo. The prevailing macrophage phenotype largely depends on the local immune status of the host. Whereas M1-polarized macrophages are considered as pro-inflammatory macrophages involved in host defense, M2 macrophages exhibit anti-inflammatory and wound-healing properties, but also promote tumor growth.We employed different models of M1 and M2 polarization: GM-CSF/LPS/IFN-gamma was used to generate primary human M1 cells and M-CSF/IL-10 to differentiate M2 monocyte-derived macrophages. PMA-differentiated THP-1 cells were polarized towards an M1 type by LPS/IFN-gamma and towards M2 by IL-10. Uptake of fluorescent silica nanoparticles (Ø 26 and 41 nm and microparticles (Ø 1.75 µm was quantified. At the concentration used (50 µg/ml, silica nanoparticles did not influence cell viability as assessed by MTT assay. Nanoparticle uptake was enhanced in M2-polarized primary human monocyte-derived macrophages compared with M1 cells, as shown by flow cytometric and microscopic approaches. In contrast, the uptake of microparticles did not differ between M1 and M2 phenotypes. M2 polarization was also associated with increased nanoparticle uptake in the macrophage-like THP-1 cell line. In accordance, in vivo polarized M2-like primary human tumor-associated macrophages (TAM obtained from lung tumors took up more nanoparticles than M1-like alveolar macrophages isolated from the surrounding lung tissue.In summary, our data indicate that the M2 polarization of macrophages promotes nanoparticle internalization. Therefore, the phenotypical differences between macrophage subsets should be taken into consideration in future investigations on nanosafety, but might also open up therapeutic perspectives allowing to specifically target M2

  10. Pulmonary Alveolar Proteinosis and tuberculosis in a diabetic patient: a rare or a seldom diagnosed association

    Directory of Open Access Journals (Sweden)

    Pereira-Silva J.L.

    2002-01-01

    Full Text Available A case of Pulmonary Alveolar Proteinosis (PAP, in association with tuberculosis, is described in a 35-year-old diabetic patient. Lung biopsy showed an intra-alveolar accumulation of PAS-positive material, and multifocal granulomas compatible with tuberculosis. The bronchoalveolar culture was positive for Mycobacterium tuberculosis. PAP results from an imbalance of the mechanisms that regulate the homeostasis of the surfactant, where specific proteins are involved, especially SP-A and SP-D, the cytokines, IL-10 and GM-CSF, in addition to alveolar macrophages and type-II pneumocytes. Chemotaxis and phagocytic capacity are reduced. PAP and diabetes share several immunological disfunctions that may increase the risk for tuberculosis. Although there are no controlled studies, the diagnosis of PAP in diabetic patients with tuberculosis must be considered.

  11. Macrophage Akt1 Kinase-Mediated Mitophagy Modulates Apoptosis Resistance and Pulmonary Fibrosis.

    Science.gov (United States)

    Larson-Casey, Jennifer L; Deshane, Jessy S; Ryan, Alan J; Thannickal, Victor J; Carter, A Brent

    2016-03-15

    Idiopathic pulmonary fibrosis (IPF) is a devastating lung disorder with increasing incidence. Mitochondrial oxidative stress in alveolar macrophages is directly linked to pulmonary fibrosis. Mitophagy, the selective engulfment of dysfunctional mitochondria by autophagasomes, is important for cellular homeostasis and can be induced by mitochondrial oxidative stress. Here, we show Akt1 induced macrophage mitochondrial reactive oxygen species (ROS) and mitophagy. Mice harboring a conditional deletion of Akt1 in macrophages (Akt1(-/-)Lyz2-cre) and Park2(-/-) mice had impaired mitophagy and reduced active transforming growth factor-β1 (TGF-β1). Although Akt1 increased TGF-β1 expression, mitophagy inhibition in Akt1-overexpressing macrophages abrogated TGF-β1 expression and fibroblast differentiation. Importantly, conditional Akt1(-/-)Lyz2-cre mice and Park2(-/-) mice had increased macrophage apoptosis and were protected from pulmonary fibrosis. Moreover, IPF alveolar macrophages had evidence of increased mitophagy and displayed apoptosis resistance. These observations suggest that Akt1-mediated mitophagy contributes to alveolar macrophage apoptosis resistance and is required for pulmonary fibrosis development. PMID:26921108

  12. Macrophage Akt1 Kinase-Mediated Mitophagy Modulates Apoptosis Resistance and Pulmonary Fibrosis.

    Science.gov (United States)

    Larson-Casey, Jennifer L; Deshane, Jessy S; Ryan, Alan J; Thannickal, Victor J; Carter, A Brent

    2016-03-15

    Idiopathic pulmonary fibrosis (IPF) is a devastating lung disorder with increasing incidence. Mitochondrial oxidative stress in alveolar macrophages is directly linked to pulmonary fibrosis. Mitophagy, the selective engulfment of dysfunctional mitochondria by autophagasomes, is important for cellular homeostasis and can be induced by mitochondrial oxidative stress. Here, we show Akt1 induced macrophage mitochondrial reactive oxygen species (ROS) and mitophagy. Mice harboring a conditional deletion of Akt1 in macrophages (Akt1(-/-)Lyz2-cre) and Park2(-/-) mice had impaired mitophagy and reduced active transforming growth factor-β1 (TGF-β1). Although Akt1 increased TGF-β1 expression, mitophagy inhibition in Akt1-overexpressing macrophages abrogated TGF-β1 expression and fibroblast differentiation. Importantly, conditional Akt1(-/-)Lyz2-cre mice and Park2(-/-) mice had increased macrophage apoptosis and were protected from pulmonary fibrosis. Moreover, IPF alveolar macrophages had evidence of increased mitophagy and displayed apoptosis resistance. These observations suggest that Akt1-mediated mitophagy contributes to alveolar macrophage apoptosis resistance and is required for pulmonary fibrosis development.

  13. Pulmonary alveolar microlithiasis with calcified pleural plaques

    Directory of Open Access Journals (Sweden)

    Malhotra Balbir

    2010-01-01

    Full Text Available Pulmonary alveolar microlithiasis (PAM is a rare disease. Herein we report a case of pulmonary alveolar microlithiasis who was suspected to have the disease on chest X-ray and was confirmed on high resolution CT and transbronchial lung biopsy. These investigations showed characteristic features of pulmonary alveolar microlithiasis with diffuse interstitial pulmonary fibrosis.

  14. Pulmonary alveolar microlithiasis with calcified pleural plaques

    OpenAIRE

    Malhotra Balbir; Sabharwal Raghu; Singh Mandeep; Singh Amarjeet

    2010-01-01

    Pulmonary alveolar microlithiasis (PAM) is a rare disease. Herein we report a case of pulmonary alveolar microlithiasis who was suspected to have the disease on chest X-ray and was confirmed on high resolution CT and transbronchial lung biopsy. These investigations showed characteristic features of pulmonary alveolar microlithiasis with diffuse interstitial pulmonary fibrosis.

  15. Yolk Sac Macrophages, Fetal Liver, and Adult Monocytes Can Colonize an Empty Niche and Develop into Functional Tissue-Resident Macrophages.

    Science.gov (United States)

    van de Laar, Lianne; Saelens, Wouter; De Prijck, Sofie; Martens, Liesbet; Scott, Charlotte L; Van Isterdael, Gert; Hoffmann, Eik; Beyaert, Rudi; Saeys, Yvan; Lambrecht, Bart N; Guilliams, Martin

    2016-04-19

    Tissue-resident macrophages can derive from yolk sac macrophages (YS-Macs), fetal liver monocytes (FL-MOs), or adult bone-marrow monocytes (BM-MOs). The relative capacity of these precursors to colonize a niche, self-maintain, and perform tissue-specific functions is unknown. We simultaneously transferred traceable YS-Macs, FL-MOs, and BM-MOs into the empty alveolar macrophage (AM) niche of neonatal Csf2rb(-/-) mice. All subsets produced AMs, but in competition preferential outgrowth of FL-MOs was observed, correlating with their superior granulocyte macrophage-colony stimulating factor (GM-CSF) reactivity and proliferation capacity. When transferred separately, however, all precursors efficiently colonized the alveolar niche and generated AMs that were transcriptionally almost identical, self-maintained, and durably prevented alveolar proteinosis. Mature liver, peritoneal, or colon macrophages could not efficiently colonize the empty AM niche, whereas mature AMs could. Thus, precursor origin does not affect the development of functional self-maintaining tissue-resident macrophages and the plasticity of the mononuclear phagocyte system is largest at the precursor stage. PMID:26992565

  16. Development of microscopic polyangiitis-related pulmonary fibrosis in a patient with autoimmune pulmonary alveolar proteinosis

    OpenAIRE

    Kinehara, Yuhei; Kida, Hiroshi; Inoue, Yoshikazu; Hirose, Masaki; Nakabayashi, Akihiko; Takeuchi, Yoshiko; Hayama, Yoshitomo; Fukushima, Kiyoharu; Hirata, Haruhiko; Inoue, Koji; Minami, Toshiyuki; Nagatomo, Izumi; Takeda, Yoshito; Funakoshi, Toshiki; Kijima, Takashi

    2014-01-01

    Background Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disease caused by the autoantibody against granulocyte-macrophage colony stimulating factor (GM-CSF). The clinical course of aPAP is variable; in severe cases, patients develop lethal respiratory failure due to pulmonary fibrosis. However, the pathogenesis of pulmonary fibrosis in aPAP has never been delineated. Case presentation Here, we describe a rare case of aPAP that was subsequently complicated by microscopic pol...

  17. Pulmonary alveolar proteinosis due to mycophenolate and cyclosporine combination therapy in a renal transplant recipient

    OpenAIRE

    Ashfaq Hasan; Raja Ram; TLN Swamy

    2014-01-01

    Pulmonary alveolar proteinosis (PAP) is an orphan disease characterized by the accumulation of excess of surfactant within alveoli and bronchioles. The primary form of PAP (P-PAP; also referred to as idiopathic or autoimmune) is the most common form. It is mediated through a circulating neutralizing antibody against granulocyte-macrophage colony-stimulating factor. Secondary PAP (S-PAP) can be induced by a host of inciting agents and is far more liable to progress to terminal respiratory fail...

  18. Pulmonary Alveolar Proteinosis in a 67-Year-Old Woman with Wegener’s Granulomatosis

    OpenAIRE

    Shiwan K. Shah; Phan, Nghi B.; Goyal, Geetinder; Sharma, Gulshan

    2010-01-01

    Mycophenolate mofetil (MM) is commonly used in patients with autoimmune diseases or who have undergone transplantation. Common side effects of MM include anemia, leukopenia, mucositis and opportunistic infections. We report an unusual case of pulmonary alveolar proteinosis (PAP) in a 67-year-old woman on MM for Wegener’s granulomatosis (WG). PAP is a disease characterized by defects in macrophage-mediated processing of surfactants, leading to accumulation of periodic acid-Schiff (PAS)-positiv...

  19. Human in vivo fluorescence microimaging of the alveolar ducts and sacs during bronchoscopy.

    Science.gov (United States)

    Thiberville, L; Salaün, M; Lachkar, S; Dominique, S; Moreno-Swirc, S; Vever-Bizet, C; Bourg-Heckly, G

    2009-05-01

    The aim of the present study was to assess fibred confocal fluorescence microscopy (FCFM) as a tool for imaging the alveolar respiratory system in vivo during bronchoscopy. A 488-nm excitation wavelength FCFM device was used in 41 healthy subjects including 17 active smokers. After topical anaesthesia, the 1.4-mm miniprobe was introduced into the bronchoscope working channel and advanced distally to the alveoli. Morphometric and cellular analyses were performed on selected frames harbouring a minimal compression effect. In vivo acinar microimaging was obtained from each lung segment except for the apical and posterior segments of both upper lobes. Reproducible patterns, corresponding to the elastic framework of the axial and peripheral interstitial systems, were recorded from 192 separate acini. The mean+/-sd thickness of the acinar elastic fibres was 10+/-2.7 microm. Alveolar mouth diameters (mean+/-sd 278+/-53 microm) were normally distributed but appeared smaller in the right upper lobe and right medial basal segment. Lobular microvessels (median diameter 90 microm) were equally distributed throughout the lungs. Alveolar macrophages were not detectable in nonsmokers, whereas a specific tobacco-tar-induced fluorescence was observed in smoking subjects, providing fine details of the alveolar walls and macrophages. A strong correlation was found between the number of cigarettes smoked per day and the amount of large and mobile macrophages observed in vivo, as well as with the intensity of the macrophage alveolitis. Fibred confocal fluorescence microscopy enables accurate exploration of the peripheral lung in vivo in both smokers and nonsmokers. PMID:19213792

  20. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

    Science.gov (United States)

    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

    2016-02-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

  1. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona;

    2010-01-01

    BACKGROUND: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release...

  2. Morphologic characteristics of pulmonary macrophages in cetaceans: particular reference to pulmonary intravascular macrophages as a newly identified type.

    Science.gov (United States)

    Kawashima, M; Kuwamura, M; Takeya, M; Yamate, J

    2004-11-01

    We examined the morphologic characteristics of pulmonary macrophages in 42 specimens of Odontoceti (Globicephala macrorhynchus, Grampus griseus, Tursiops truncatus, Stenella attenuata, Stenella coeruleoalba, Berardius bairdii), using light and electron microscopes as well as immunohistochemistry with SRA-E5. SRA-E5-positive alveolar macrophages and pulmonary interstitial macrophages contained graphitic soots, indicating the clearance of airborne, aspirated foreign bodies. Pulmonary intravascular macrophages (PIMs), positive with SRA-E5, were present within pulmonary capillaries, attaching to applied endothelial cells by cell junctions. They showed cytoplasmic tubular structures of micropinocytosis vermiformis and erythrophagocytosis, indicating their contributory role in the clearance of blood-borne particles. The uptake of pathogens by PIMs may be associated with the inducement of acute lung injury, especially bacterial infectious pneumonia. This study revealed for the first time the presence of PIMs in cetaceans. PMID:15557077

  3. Influence of moxifloxacin on lipoteichoic acid induced apoptosis and expression of inflammatory cytokines in human alveolar macrophage%莫西沙星对脂磷壁酸诱导的人肺泡巨噬细胞凋亡及炎症因子释放的影响

    Institute of Scientific and Technical Information of China (English)

    罗进梅; 吴本权; 刘慧; 李洪涛; 黄静; 朱家馨; 张天托

    2012-01-01

    Objective To investigate the lipoteichoic acid(LTA) induced apoptosis and the expression of inflammatory cytokines in human alveolar macrophage (AM) and the anti-apoptotic and anti-inflamatory effect of moxifloxacin (MXF).Methods Obtained human AM from bronchoalveolar lavage and used MTT assay to observe the effects of LTA and MXF on cell activity,optical microscope to investigate the change of the cell morphology,flow cytometry to assess cell apoptosis,RT-PCR to detect the mRNA levels of TLR2,IL-1 β,IL-8 and TNF-α,ELISA for the production of IL-8 to exam RT-PCR.Results LTA showed cytotoxicity on AM in a dose-dependent manner ( P<0.05 ) ; MXF inhibited the effect of LTA without cytotoxicicy ( P<0.05 ).LTA promoted apoptosis ( P<0.05 ) and the mRNA expressions of TRL2,IL-1 β,IL-8 and TNF-α significantly in AM (P<0.05),the peaks and peak time ofthe above factors were (3.56±0.03) at 12 h,(46.63±7.06) at 6 h,(28.07±1.24) at 12 h and (2.34 ±0.50) at 3 h respectively and increased the release of IL-8 protein level at 24 h (P<0.05).MXF inhibited the cell apoptosis and the above mRNA expression at 12h ( P<0.05 ),and inhibited the IL-8 protein level at 24 h( P<0.05 ).Conclusion LTA showed cytotoxicity on AM,induced AM apoptosis and increased the expression of TLR2,IL-I β,IL-8 and TNF-α of AM ; MXF could protect AM through inhibiting of the above effects and may play a key role beside bactericidal effect in gram-positive bacteria pneumonia.%目的 探讨脂磷壁酸(LTA)对人肺泡巨噬细胞(AM)凋亡及炎症因子释放的影响和莫西沙星(MXF)对其反应的抑制作用.方法 收集、提纯及体外培养人AM,LTA刺激4h后,加或不加MXF与其共孵育,于各实验终点用MTT法计算细胞相对活力,光学显微镜观察细胞形态,流式细胞术检测细胞凋亡率,RT-PCR法检测TLR2、IL-1β、IL-8及TNF-α的mRNA水平,ELISA检测IL-8蛋白水平,验证RT-PCR.结果 LTA对AM有细胞毒性,并呈浓度递增关系(P<0

  4. Characterization of Legionella pneumophila pmiA, a Gene Essential for Infectivity of Protozoa and Macrophages

    OpenAIRE

    Miyake, Masaki; Watanabe, Takurou; Koike, Hitomi; Molmeret, Maëlle; Imai, Yasuyuki; Abu Kwaik, Yousef

    2005-01-01

    The ability of Legionella pneumophila to cause pneumonia is dependent on intracellular replication within alveolar macrophages. The Icm/Dot secretion apparatus is essential for the ability of L. pneumophila to evade endocytic fusion, to remodel the phagosome by the endoplasmic reticulum (ER), and to replicate intracellularly. Protozoan and macrophage infectivity (pmi) mutants of L. pneumophila, which include 11 dot/icm mutants, exhibit defects in intracellular growth and replication within bo...

  5. Homotypic Lysosome Fusion in Macrophages: Analysis Using an In Vitro Assay

    OpenAIRE

    Diane M Ward; Jonathan D Leslie; Kaplan, Jerry

    1997-01-01

    Lysosomes are dynamic structures capable of fusing with endosomes as well as other lysosomes. We examined the biochemical requirements for homotypic lysosome fusion in vitro using lysosomes obtained from rabbit alveolar macrophages or the cultured macrophage-like cell line, J774E. The in vitro assay measures the formation of a biotinylated HRP–avidin conjugate, in which biotinylated HRP and avidin were accumulated in lysosomes by receptor-mediated endocytosis. We determined that lysosome fusi...

  6. Unsuspected pulmonary alveolar proteinosis in a patient with acquired immunodeficiency syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Niazi Masooma

    2011-02-01

    Full Text Available Abstract Introduction Diffuse lung infiltrates are a common finding in patients with acquired immunodeficiency syndrome and causes range from infectious processes to malignancies or interstitial lung diseases. Pulmonary alveolar proteinosis is a rare pulmonary disorder rarely reported in patients infected with human immunodeficiency virus. Secondary pulmonary alveolar proteinosis is associated with conditions involving functional impairment or reduced numbers of alveolar macrophages. It can be caused by hematologic malignancies, inhalation of toxic dust, fumes or gases, infectious or pharmacologic immunosuppression, or lysinuric protein intolerance. Case presentation A 42-year-old African American man infected with human immunodeficiency virus was admitted with chronic respiratory symptoms and diffuse pulmonary infiltrates. Chest computed tomography revealed bilateral spontaneous pneumothoraces, for which he required bilateral chest tubes. Initial laboratory investigations did not reveal any contributory conditions. Histological examination of a lung biopsy taken during video-assisted thoracoscopy showed pulmonary alveolar proteinosis concurrent with cytomegalovirus pneumonitis. After ganciclovir treatment, our patient showed radiologic and clinical improvement. Conclusion The differential diagnosis for patients with immunosuppression and lung infiltrates requires extensive investigations. As pulmonary alveolar proteinosis is rare, the diagnosis can be easily missed. Our case highlights the importance of invasive investigations and histology in the management of patients infected with human immunodeficiency virus and pulmonary disease who do not respond to empiric therapy.

  7. Enhanced superoxide release and tumoricidal activity by a postlavage, in situ pulmonary macrophage population in response to activation by Mycobacterium bovis BCG exposure.

    Science.gov (United States)

    Drath, D B

    1985-07-01

    The monocytic phagocyte population of rat lungs is heterogeneous. In addition to the freely lavagable alveolar macrophages, there is a fixed in situ tissue-associated subpopulation of pulmonary macrophages. The response of this subpopulation to classical macrophage activation by Mycobacterium bovis BCG exposure was monitored. Results indicate that this population can be activated both metabolically and functionally, as evidenced by enhanced release of superoxide anions and demonstrable tumoricidal activity against syngeneic and xenogeneic target cells. The pattern of metabolic activation of in situ tissue-associated macrophages differed somewhat from that of alveolar macrophages and was observed only after subsequent exposure of the cells to either zymosan particles or phorbol myristate acetate. Upon such exposure, the activated zymosan-treated tissue macrophages released approximately twice as much superoxide as the nonactivated cells and amounts comparable to the amounts released by activated alveolar macrophages. The tissue macrophages also displayed greater levels of cytotoxicity toward xenogenic targets than the alveolar cells and may have an important role in preventing microbial or tumor cell colonization of respiratory systems. PMID:2989181

  8. The role of macrophage derived growth factors in pulmonary fibrosis

    International Nuclear Information System (INIS)

    Factors released from rat alveolar macrophages exposed to high (95 μg/mL) concentrations of the fibrogenic agent, nickel subsulfide, were found to inhibit the proliferation of cultured lung epithelial cells and stimulate the growth of fibroblasts. Such factors, if present in the alveoli of rats exposed by inhalation to nickel subsulfide in vivo, may play a role in inhibiting re-epithelization of nickel-damaged lungs and in stimulating fibroblast proliferation, leading to pulmonary fibrosis. (author)

  9. Alveolar hypoventilation treated with medroxyprogesterone.

    OpenAIRE

    Milerad, J; Lagercrantz, H.; Löfgren, O

    1985-01-01

    Two children aged 1 and 20 months developed alveolar hypoventilation syndrome. They suffered severe apnoeic episodes and periodically required assisted ventilation. Their ventilatory response to carbon dioxide was lower than that of normal children and the transcutaneous oxygen tension during sleep was well below the normal range. Treatment with medroxyprogesterone acetate resulted in an improved response to carbon dioxide, and assisted ventilation was no longer needed. Oxygen and carbon diox...

  10. [Alveolar sarcoma. Report of a case].

    Science.gov (United States)

    Devisme, L; Mensier, E; Bisiau, S; Bloget, F; Gosselin, B

    1996-01-01

    Alveolar soft part sarcoma occurs mostly in the deep soft tissues. An unusual case of primary pulmonary alveolar soft part sarcoma is reported. A 39-year-old woman presented with thoracic pain revealing the tumor. The left lower lobe was surgically resected. The microscopic features of this tumor, including characteristic alveolar pattern and the PAS-positive crystals were typical of alveolar soft part sarcoma. Immunohistochemically, granular cytoplasmic reactivities were observed with antibodies against vimentin, myoglobin, methionine-enkephalin, S100 protein and neuron-specific-enolase. Electron microscopic study demonstrated numerous crystallized structures in the tumor cell cytoplasm. This is the third case of pulmonary alveolar soft part sarcoma, one arising from the pulmonary vein. The histogenesis of alveolar soft part sarcoma is still debated. Our case does not allow distinction between myogenic or neural origin of this tumor.

  11. Autoantibody-Mediated Pulmonary Alveolar Proteinosis in Rasgrp1-Deficient Mice.

    Science.gov (United States)

    Ferretti, Andrew; Fortwendel, Jarrod R; Gebb, Sarah A; Barrington, Robert A

    2016-07-15

    Pulmonary alveolar proteinosis (PAP) is a rare lung syndrome caused by the accumulation of surfactants in the alveoli. The most prevalent clinical form of PAP is autoimmune PAP (aPAP) whereby IgG autoantibodies neutralize GM-CSF. GM-CSF is a pleiotropic cytokine that promotes the differentiation, survival, and activation of alveolar macrophages, the cells responsible for surfactant degradation. IgG-mediated neutralization of GM-CSF thereby inhibits alveolar macrophage homeostasis and function, leading to surfactant accumulation and innate immunodeficiency. Importantly, there are no rodent models for this disease; therefore, underlying immune mechanisms regulating GM-CSF-specific IgG in aPAP are not well understood. In this article, we identify that autoimmune-prone Rasgrp1-deficient mice develop aPAP: 1) Rasgrp1-deficient mice exhibit reduced pulmonary compliance and lung histopathology characteristic of PAP; 2) alveolar macrophages from Rasgrp1-deficient mice are enlarged and exhibit reduced surfactant degradation; 3) the concentration of GM-CSF-specific IgG is elevated in both serum and bronchoalveolar lavage fluid from Rasgrp1-deficient mice; 4) GM-CSF-specific IgG is capable of neutralizing GM-CSF bioactivity; and 5) Rasgrp1-deficient mice also lacking CD275/ICOSL, a molecule necessary for conventional T cell-dependent Ab production, have reduced GM-CSF-specific autoantibody and do not develop PAP. Collectively, these studies reveal that Rasgrp1-deficient mice, to our knowledge, represent the first rodent model for aPAP. PMID:27279372

  12. Alveolar septal pulmonary amyloidosis: a case report

    International Nuclear Information System (INIS)

    Primary pulmonary amyloidosis is a rare diesase, and is classified as either tracheobronchial or parenchymal; the latter is also divided into nodular and diffuse alveolar septal forms. The alveolar septal form is extremely rare and usually produces reticular and nodular opacities. We describe a case of alveolar septal pulmonary amyloidosis manifested as multiple small nodules on chest radiograph and disseminated micronodules mainly in centrilobular and subpleural location without reticular opacities, on HRCT

  13. Enhanced superoxide release and tumoricidal activity by a postlavage, in situ pulmonary macrophage population in response to activation by Mycobacterium bovis BCG exposure.

    OpenAIRE

    Drath, D B

    1985-01-01

    The monocytic phagocyte population of rat lungs is heterogeneous. In addition to the freely lavagable alveolar macrophages, there is a fixed in situ tissue-associated subpopulation of pulmonary macrophages. The response of this subpopulation to classical macrophage activation by Mycobacterium bovis BCG exposure was monitored. Results indicate that this population can be activated both metabolically and functionally, as evidenced by enhanced release of superoxide anions and demonstrable tumori...

  14. CD163-L1 is an endocytic macrophage protein strongly regulated by mediators in the inflammatory response

    DEFF Research Database (Denmark)

    Moeller, Jesper B; Nielsen, Marianne J; Reichhardt, Martin P;

    2012-01-01

    on large subsets of macrophages, but in contrast to CD163 the expression is low or absent in monocytes and in alveolar macrophages, glia, and Kupffer cells. The expression of CD163-L1 increases when cultured monocytes are M-CSF stimulated to macrophages, and the expression is further increased by the acute...... exhibits similarity to CD163 in terms of structure and regulated expression in cultured monocytes but shows clear differences compared with the known CD163 ligand preferences and expression pattern in the pool of tissue macrophages. We postulate that CD163-L1 functions as a scavenger receptor for one...

  15. M1-like Macrophage Polarization Promotes Orthodontic Tooth Movement.

    Science.gov (United States)

    He, D; Kou, X; Yang, R; Liu, D; Wang, X; Luo, Q; Song, Y; Liu, F; Yan, Y; Gan, Y; Zhou, Y

    2015-09-01

    Macrophages play a crucial role in inflammatory-mediated bone loss. Orthodontic tooth movement (OTM) is associated with inflammatory bone remodeling. However, whether and how macrophages contribute to mechanical force-induced OTM remains unknown. In this study, we hypothesized that polarization of M1-like macrophages may contribute to the OTM. Orthodontic nickel-titanium springs were applied to the upper first molars of rats or mice to induce OTM. The distance of OTM gradually increased after mechanical force was applied to the rats for 5 and 10 d. M1-like macrophage polarization and expression of M1 cytokine tumor necrosis factor (TNF)-α also increased after force application. More importantly, monocyte/macrophage depletion in mice by injection of clodronate liposomes decreased the distance of OTM and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68(+) macrophages, accompanied by reduced expressions of M1 markers TNF-α and inducible nitric oxide synthase (iNOS), whereas systemic transfusion of M1 macrophages in mice increased them. Further experiments showed that injection of recombinant TNF-α increased the distance of OTM and the number of TRAP-positive osteoclasts and CD68(+) macrophages, as well as upregulated the expression of TNF-α and iNOS. Blockage of TNF-α by etanercept injection reduced the distance of OTM and the number of TRAP-positive osteoclasts and CD68(+) macrophages, as well as decreased the levels of TNF-α and iNOS. These data suggest that M1-like macrophage polarization promotes alveolar bone resorption and consequent OTM after mechanical force application. PMID:26124217

  16. Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice.

    Science.gov (United States)

    Glasser, Stephan W; Senft, Albert P; Whitsett, Jeffrey A; Maxfield, Melissa D; Ross, Gary F; Richardson, Theresa R; Prows, Daniel R; Xu, Yan; Korfhagen, Thomas R

    2008-07-01

    To determine the role of surfactant protein C (SP-C) in host defense, SP-C-deficient (Sftpc-/-) mice were infected with the pulmonary pathogen Pseudomonas aeruginosa by intratracheal injection. Survival of young, postnatal day 14 Sftpc-/- mice was decreased in comparison to Sftpc+/+ mice. The sensitivity to Pseudomonas bacteria was specific to the 129S6 strain of Sftpc-/- mice, a strain that spontaneously develops interstitial lung disease-like lung pathology with age. Pulmonary bacterial load and leukocyte infiltration were increased in the lungs of Sftpc-/- mice 24 h after infection. Early influx of polymorphonuclear leukocytes in the lungs of uninfected newborn Sftpc-/- mice relative to Sftpc+/+ mice indicate that the lack of SP-C promotes proinflammatory responses in the lung. Mucin expression, as indicated by Alcian blue staining, was increased in the airways of Sftpc-/- mice following infection. Phagocytic activity of alveolar macrophages from Sftpc-/- mice was reduced. The uptake of fluorescent beads in vitro and the number of bacteria phagocytosed by alveolar macrophages in vivo was decreased in the Sftpc-/- mice. Alveolar macrophages from Sftpc-/- mice expressed markers of alternative activation that are associated with diminished pathogen response and advancing pulmonary fibrosis. These findings implicate SP-C as a modifier of alveolar homeostasis. SP-C plays an important role in innate host defense of the lung, enhancing macrophage-mediated Pseudomonas phagocytosis, clearance and limiting pulmonary inflammatory responses. PMID:18566429

  17. Aggregation of macrophages and fibroblasts is inhibited by a monoclonal antibody to the hyaluronate receptor

    Energy Technology Data Exchange (ETDEWEB)

    Green, S.J.; Underhill, C.B. (Georgetown Univ. Medical Center, Washington, DC (USA)); Tarone, G. (Univ. of Turin (Italy))

    1988-10-01

    To examine the role of the hyaluronate receptor in cell to cell adhesion, the authors have employed the K-3 monoclonal antibody (MAb) which specifically binds to the hyaluronate receptor and blocks its ability to interact with hyaluronate. In the first set of experiments, they investigated the spontaneous aggregation of SV-3T3 cells, which involves two distinct mechanisms, one of which is dependent upon the presence of divalent cation and the other is independent. The divalent cation-independent aggregation was found to be completely inhibited by both intact and Fab fragments of the K-3 MAb. In contrast, the K-3 MAb had no effect on the divalent cation-dependent aggregation of cells. In a second set of experiments, we examined alveolar macrophages. The presence of hyaluronate receptors on alveolar macrophages was demonstrated by the fact that detergent extracts of these cells could bind ({sup 3})hyaluronate, and this binding was blocked by the K-3 MAb. Immunoblot analysis of alveolar macrophages showed that the hyaluronate receptor had a M{sub r} of 99,500, which is considerably larger than the 85,000 M{sub r} for that on BHK cells. When hyaluronate was added to suspensions of alveolar macrophages, the cells were induced to aggregate. This effect was inhibited by the K-3 MAb, suggesting that the hyaluronate-induced aggregation was mediated by the receptor.

  18. Human Lung Hydrolases Delineate Mycobacterium tuberculosis–Macrophage Interactions and the Capacity To Control Infection

    OpenAIRE

    Arcos, Jesus; Sasindran, Smitha J.; Fujiwara, Nagatoshi; Turner, Joanne; Schlesinger, Larry S; Torrelles, Jordi B.

    2011-01-01

    Pulmonary surfactant contains homeostatic and antimicrobial hydrolases. When Mycobacterium tuberculosis is initially deposited in the terminal bronchioles and alveoli, as well as following release from lysed macrophages, bacilli are in intimate contact with these lung surfactant hydrolases. We identified and measured several hydrolases in human alveolar lining fluid and lung tissue that, at their physiological concentrations, dramatically modified the M. tuberculosis cell envelope. Independen...

  19. [Pulmonary alveolar microlithiasis: Report of one case].

    Science.gov (United States)

    Fernández F, Cristina; Salinas F, Mauricio; de Grazia K, José Andrés; Díaz P, Juan Carlos

    2014-05-01

    Pulmonary alveolar microlithiasis is an extremely rare disease characterized by intra-alveolar accumulation of calcified spherical particles (called microliths), due to a mutation of the gene encoding a membrane transport protein of the alveolar surface. Most patients are asymptomatic at diagnosis. The course of the disease is slowly progressive, with development of pulmonary fibrosis and respiratory failure. The "sandstorm" pattern is the characteristic finding of this disease. We report a 39-year-old female presenting with progressive dyspnea. A chest X ray showed ground-glass opacities and a high resolution CT scan showed numerous calcified lung micronodules. A surgical lung biopsy confirmed the diagnosis of pulmonary alveolar microlithiasis. PMID:25427025

  20. Immune modulation with sulfasalazine attenuates immunopathogenesis but enhances macrophage-mediated fungal clearance during Pneumocystis pneumonia.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available Although T cells are critical for host defense against respiratory fungal infections, they also contribute to the immunopathogenesis of Pneumocystis pneumonia (PcP. However, the precise downstream effector mechanisms by which T cells mediate these diverse processes are undefined. In the current study the effects of immune modulation with sulfasalazine were evaluated in a mouse model of PcP-related Immune Reconstitution Inflammatory Syndrome (PcP-IRIS. Recovery of T cell-mediated immunity in Pneumocystis-infected immunodeficient mice restored host defense, but also initiated the marked pulmonary inflammation and severe pulmonary function deficits characteristic of IRIS. Sulfasalazine produced a profound attenuation of IRIS, with the unexpected consequence of accelerated fungal clearance. To determine whether macrophage phagocytosis is an effector mechanism of T cell-mediated Pneumocystis clearance and whether sulfasalazine enhances clearance by altering alveolar macrophage phagocytic activity, a novel multispectral imaging flow cytometer-based method was developed to quantify the phagocytosis of Pneumocystis in vivo. Following immune reconstitution, alveolar macrophages from PcP-IRIS mice exhibited a dramatic increase in their ability to actively phagocytose Pneumocystis. Increased phagocytosis correlated temporally with fungal clearance, and required the presence of CD4(+ T cells. Sulfasalazine accelerated the onset of the CD4(+ T cell-dependent alveolar macrophage phagocytic response in PcP-IRIS mice, resulting in enhanced fungal clearance. Furthermore, sulfasalazine promoted a TH2-polarized cytokine environment in the lung, and sulfasalazine-enhanced phagocytosis of Pneumocystis was associated with an alternatively activated alveolar macrophage phenotype. These results provide evidence that macrophage phagocytosis is an important in vivo effector mechanism for T cell-mediated Pneumocystis clearance, and that macrophage phenotype can be altered

  1. Household air pollution causes dose-dependent inflammation and altered phagocytosis in human macrophages.

    Science.gov (United States)

    Rylance, Jamie; Fullerton, Duncan G; Scriven, James; Aljurayyan, Abdullah N; Mzinza, David; Barrett, Steve; Wright, Adam K A; Wootton, Daniel G; Glennie, Sarah J; Baple, Katy; Knott, Amy; Mortimer, Kevin; Russell, David G; Heyderman, Robert S; Gordon, Stephen B

    2015-05-01

    Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies. We used human alveolar macrophages obtained from healthy Malawian adults exposed naturally to household air pollution and compared them with human monocyte-derived macrophages exposed in vitro to respirable-sized particulates. Cellular inflammatory response was assessed by IL-6 and IL-8 production in response to particulate challenge; phagosomal function was tested by uptake and oxidation of fluorescence-labeled beads; ingestion and killing of Streptococcus pneumoniae and Mycobacterium tuberculosis were measured by microscopy and quantitative culture. Particulate ingestion was quantified by digital image analysis. We were able to reproduce the carbon loading of naturally exposed alveolar macrophages by in vitro exposure of monocyte-derived macrophages. Fine carbon black induced IL-8 release from monocyte-derived and alveolar macrophages (P < 0.05) with similar magnitude responses (log10 increases of 0.93 [SEM = 0.2] versus 0.74 [SEM = 0.19], respectively). Phagocytosis of pneumococci and mycobacteria was impaired with higher particulate loading. High particulate loading corresponded with a lower oxidative burst capacity (P = 0.0015). There was no overall effect on killing of M. tuberculosis. Alveolar macrophage function is altered by particulate loading. Our macrophage model is comparable morphologically to the in vivo uptake of particulates. Wood smoke-exposed cells demonstrate reduced phagocytosis, but unaffected mycobacterial killing, suggesting defects related to chronic wood smoke inhalation limited to specific innate immune functions.

  2. Technical and harmonic analysis of Carl Czerny op. 299 number 34 etude

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    Mehmet Serkan Umuzdas

    2012-11-01

    Full Text Available In this study, the 34th etude of the book Czerny Op. 299 that is one of the commonly employed books in the piano training was analysed in terms of technique and harmony. The etude was examined in terms of its technical features and contributions to technical development. If an etude is analysed before it is played, time and effort can be amanged much more efficiently. In turn, it may contribute to play the etude or work in accordance with its objectives and to produce outcomes. The aims of this study are to make the students aware of the goals and methods of etudes and to provide them with the suggestions for studying. It is suggested that any etude written with the 2/4 rhythm pattern should be played very vividly and energytically. Any etude written in the octave width of 5.5 is made up of 43 scales in two section. The etude is composed of two sections, each with four sentences and two periods. It also involves 43 scales. Of them, 16 scales are in the first section and the remaining 27 scales are in the second section. The etude has very regular system in terms of harmonic continuity and motives. It has a homogenious pattern in terms of the order of the sentences with half-decsion and those with full-decision.

  3. Computed tomographic imaging of pulmonary alveolar proteinosis

    International Nuclear Information System (INIS)

    Pulmonary alveolar proteinosis is a rare disease of uncertain etiology. The computed tomographic image is characterized by geographically sharply delineated alveolar infiltrates, faint, ground-glass-like parenchymal turbidity, with well bordered interstitial structures and recesses in the subpleural space. (orig.)

  4. CT quantification of pulmonary alveolar microlithiasis

    International Nuclear Information System (INIS)

    Pulmonary alveolar microlithiasis is a rare, familial disease with massive symmetrical intra-alveolar calcium deposition. Conventional CT findings and CT measurements with a dual energy technique were carried out in a 26-year-old patient suffering from this disease. The importance of the findings in the differential diagnosis and for estimating the progression and prognosis of the disease is discussed. (orig.)

  5. Pulmonary alveolar microlithiasis in children

    International Nuclear Information System (INIS)

    Two asymptomatic Turkish sibs are presented, a 4-year-old boy and his 7-year-old sister, with pulmonary alveolar microlithiasis (PAM) confirmed by transbronchial lung biopsy and bronchoalveolar lavage. Chest radiographs and high resolution CT demonstrated wide-spread intra-alveolar calcifications in both lungs. The lesions were sharply defined and less than 1 mm in diameter. CT documented a high concentration of microliths along the bronchovascular bundles, the intralobular fissue and the (sub)pleural lung parenchyma. The combination of bronchoalveolar lavage and roentgenographic appearance in high resolution CT are characteristic and pathognomonic, and can confirm the diagnosis. The more severe changes in the elder sib and the radiographic controls suggest that the pulmonary disease may be progressive in our patients. The described family of consanguineous, unaffected parents with two affected and one healthy child confirmed the autosomal recessive inheritance of PAM (McKusick 265100). In addition, the affected girl had autosomal recessive Waardenburg-anophthalmia syndrome (McKusick 206920), raising the question of whether this is a chance occurrence or possibly a contiguous gene syndrome. (orig.)

  6. Pulmonary alveolar microlithiasis in children

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, H. [Center of Diagnostic Radiology, Frankfurt Univ. (Germany); Loercher, U. [Center of Diagnostic Radiology, Frankfurt Univ. (Germany); Kitz, R. [Center of Pediatrics, Frankfurt Univ. (Germany); Zielen, S. [Center of Pediatrics, Frankfurt Univ. (Germany); Ahrens, P. [Center of Pediatrics, Frankfurt Univ. (Germany); Koenig, R. [Inst. of Human Genetics, Frankfurt Univ. (Germany)

    1996-01-01

    Two asymptomatic Turkish sibs are presented, a 4-year-old boy and his 7-year-old sister, with pulmonary alveolar microlithiasis (PAM) confirmed by transbronchial lung biopsy and bronchoalveolar lavage. Chest radiographs and high resolution CT demonstrated wide-spread intra-alveolar calcifications in both lungs. The lesions were sharply defined and less than 1 mm in diameter. CT documented a high concentration of microliths along the bronchovascular bundles, the intralobular fissue and the (sub)pleural lung parenchyma. The combination of bronchoalveolar lavage and roentgenographic appearance in high resolution CT are characteristic and pathognomonic, and can confirm the diagnosis. The more severe changes in the elder sib and the radiographic controls suggest that the pulmonary disease may be progressive in our patients. The described family of consanguineous, unaffected parents with two affected and one healthy child confirmed the autosomal recessive inheritance of PAM (McKusick 265100). In addition, the affected girl had autosomal recessive Waardenburg-anophthalmia syndrome (McKusick 206920), raising the question of whether this is a chance occurrence or possibly a contiguous gene syndrome. (orig.)

  7. Networked T cell death following macrophage infection by Mycobacterium tuberculosis.

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    Stephen H-F Macdonald

    Full Text Available BACKGROUND: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. METHODOLOGY/PRINCIPAL FINDINGS: We found that lymphopenia (<1.5 × 10(9 cells/l was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. CONCLUSIONS: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as

  8. Dose repartition in alveoli, alveolar ducts and bronchi of rats exposed to radon and its progeny, preliminary results

    OpenAIRE

    Bisson, Michèle; Fritsch, P; Morlier, J.P.; Sabattie, P.; Tredaniel, J.; Richard-Le Naour, H.; Monchaux, G.

    1995-01-01

    Recently, micronuclei scoring has been performed to estimate doses delivered to the lungs after heterogenous irradiation induced after inhalation of radon and its progeny. These studies were limited to the deep lung after either extraction of alveolar macrophages (AM) by lavage (Taya et al., 1994, Johnson and Newton, 1994) or enzymatic dissociation of lung cells to initiate fibroblast cultures (Khan et al., 1994). Dose estimates were performed after comparison with micronuclei formation induc...

  9. Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense Pathways in Rat Alveolar Type II Pneumocytes

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    Alexis Valauri-Orton

    2015-01-01

    Full Text Available Dichloroacetate (DCA is a water purification byproduct that is known to be hepatotoxic and hepatocarcinogenic and to induce peripheral neuropathy and damage macrophages. This study characterizes the effects of the haloacetate on lung cells by exposing rat alveolar type II (L2 cells to 0–24 mM DCA for 6–24 hours. Increasing DCA concentration and the combination of increasing DCA concentration plus longer exposures decrease measures of cellular health. Length of exposure has no effect on oxidative stress biomarkers, glutathione, SOD, or CAT. Increasing DCA concentration alone does not affect total glutathione or its redox ratio but does increase activity in the SOD/CAT oxidative stress defense pathway. These data suggest that alveolar type II cells rely on SOD and CAT more than glutathione to combat DCA-induced stress.

  10. [Cough and hypoxemia as clinical manifestation of pulmonary alveolar proteinosis. Clinical case report].

    Science.gov (United States)

    Nieto, Mary; Dicembrino, Manuela; Ferraz, Rubén; Romagnoli, Fernando; Giugno, Hilda; Ernst, Glenda; Siminovich, Monica; Botto, Hugo

    2016-06-01

    Alveolar proteinosis is a rare chronic lung disease, especially in children, characterized by abnormal accumulation of lipoproteins and derived surfactant in the intra-alveolar space that generates a severe reduction of gas exchange. Idiopathic presentation form constitutes over 90% of cases, a phenomenon associated with production of autoimmune antibodies directed at the receptor for granulocyte-macrophage colony-stimulating factor. A case of a girl of 5 years of age treated because of atypical pneumonia with unfavorable evolution due to persistent hypoxemia is presented. The diagnosis is obtained through pathologic examination of lung biopsy by thoracotomy, as treatment is carried out by 17bronchopulmonary bronchoscopy lavages and the patient evidences marked clinical improvement. PMID:27164343

  11. Whole Lung Lavage in a Pulmonary Alveolar Proteinosis Patient with Severe Respiratory Failure.

    Science.gov (United States)

    Önemli, Canan Salman; Çatal, Deniz Ayhan

    2016-04-01

    Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease that develops as a result of defects in the clearance of surfactant by alveolar macrophages. The accumulation of lipid- and protein-rich substances in the alveoli constitutes the main pathology of this disease. PAP has three types of aetiology: autoimmune (primary), congenital and secondary. The most common form in adults is autoimmune PAP. Whole lung lavage is a commonly performed method for treatment of this form of disease, especially in more severe cases. Performed under general anaesthesia, the material deposited in the alveoli is removed by washing. In this paper, we present a whole lung lavage under anaesthesia in a PAP patient who had severe respiratory failure. PMID:27366571

  12. Enhanced macrophage-fibroblast interactions in the pulmonary interstitium increases fibrosis after silica injection to monocyte-depleted mice

    International Nuclear Information System (INIS)

    The role of interstitial vs. alveolar macrophages in the generation of pulmonary fibrosis after silica was examined. Using whole body irradiation to delay the inflammatory response and so retard particulate clearance, many more instilled silica particles reached the interstitial macrophages in the first 2 weeks than after silica alone. This was followed by greatly increased fibroblast proliferation and deposition of collagen in the irradiation plus silica group, which developed large interstitial granulomas at the sites of silica retention. Although alveolar macrophages containing silica were seen in both silica groups, more interstitial particles were observed after combined irradiation and silica, significantly more silica was recovered in a residue from the lungs at 16 weeks, and pulmonary fibrosis at 8-16 weeks was greater than in all other groups. The results indicate that increased fibroblast growth and collagen synthesis in vivo are associated with phagocytosis of silica by interstitial macrophages rather than by free alveolar macrophages. It is suggested that transfer of a macrophages-derived growth factor to fibroblasts is more efficient when it occurs within the pulmonary interstitium

  13. A case of pulmonary alveolar microlithiasis

    International Nuclear Information System (INIS)

    A case of pulmonary alveolar microlithiasis is reported. A 33-year-old male visited our clinic because of cough and sore throat. The chest X-ray showed granular micronodulation diffusely disseminated throughout the lung fields. On the eighth day since admission, cough and sore throat disappeared. Pulmonary alveolar microlithiasis was confirmed by transbronchial lung biopsy. Bronchoalveolar lavage (BAL) was performed, and the differential cell count of the BAL fluid showed 74.3 % eosinophilia. Furthermore, 67Ga-citrate scintigraphy revealed diffuse uptake throughout the lung fields. Whether these findings are common in pulmonary alveolar microlithiasis or not is considered to be an unanswered problem. (author)

  14. Integrity of the alveolar-capillary barrier and alveolar surfactant system in smokers.

    OpenAIRE

    Schmekel, B; Bos, J.A.; A. R. Khan; Wohlfart, B; Lachmann, B.; Wollmer, P.

    1992-01-01

    BACKGROUND: The permeability of the alveolar-capillary barrier to technetium-99m labelled diethylenetriamine pentaacetate (99mTc DTPA) is known to be greatly increased in smokers, but the underlying mechanism is poorly understood. Abnormal permeability of the alveolar epithelium as well as impaired surfactant function has been suggested. The purpose of this study was to examine transudation of urea and albumin into the alveoli and alveolar surfactant function in smokers and non-smokers and to...

  15. Comparison of lung alveolar and tissue cells in silica-induced inflammation.

    Science.gov (United States)

    Sjöstrand, M; Absher, P M; Hemenway, D R; Trombley, L; Baldor, L C

    1991-01-01

    The silicon dioxide mineral, cristobalite (CRS) induces inflammation involving both alveolar cells and connective tissue compartments. In this study, we compared lung cells recovered by whole lung lavage and by digestion of lung tissue from rats at varying times after 8 days of exposure to aerosolized CRS. Control and exposed rats were examined between 2 and 36 wk after exposure. Lavaged cells were obtained by bronchoalveolar lavage with phosphate-buffered saline. Lung wall cells were prepared via collagenase digestion of lung tissue slices. Cells from lavage and lung wall were separated by Percoll density centrifugation. The three upper fractions, containing mostly macrophages, were cultured, and the conditioned medium was assayed for effect on lung fibroblast growth and for activity of the lysosomal enzyme, N-acetyl-beta-D-glucosaminidase. Results demonstrated that the cells separated from the lung walls exhibited different reaction patterns compared with those cells recovered by lavage. The lung wall cells exhibited a progressive increase in the number of macrophages and lymphocytes compared with a steady state in cells of the lung lavage. This increase in macrophages apparently was due to low density cells, which showed features of silica exposure. Secretion of a fibroblast-stimulating factor was consistently high by lung wall macrophages, whereas lung lavage macrophages showed inconsistent variations. The secretion of NAG was increased in lung lavage macrophages, but decreased at most observation times in lung wall macrophages. No differences were found among cells in the different density fractions regarding fibroblast stimulation and enzyme secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. A very rare cause of dyspnea with a unique presentation on a computed tomography scan of the chest: macrophage activation syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Brandao-Neto, Rodrigo Antonio [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Clinical Emergency Dept.; Santana, Alfredo Nicodemos Cruz; Danilovic, Debora Lucia Seguro; Mendonca, Berenice Bilharinho de [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina]. E-mail: alfredonicodemos@hotmail.com; Bernardi, Fabiola Del Carlo [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. of Pathology; Barbas, Carmen Silvia Valente [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Dept. of Pulmonology

    2008-02-15

    Macrophage activation syndrome is a rare and potentially life-threatening disease. It occurs due to immune dysregulation manifested as excessive macrophage proliferation, typically causing hepatosplenomegaly, pancytopenia and hepatic dysfunction. Here, we report an unusual case of macrophage activation syndrome presenting as dyspnea, as well as (reported here for the first time) high resolution computed tomography findings of an excavated nodule, diffuse ground glass opacities and consolidations (mimicking severe pneumonia or alveolar hemorrhage). The patient was successfully treated with human immunoglobulin. We recommend that macrophage activation syndrome be considered in the differential diagnosis of respiratory failure. Rapid diagnosis and treatment are essential to achieving favorable outcomes in patients with this syndrome. (author)

  17. Alveolar hydatid cyst: A case report

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    Behiye Zarif-Zakerian

    2010-06-01

    Full Text Available Alveolar hydatid cyst is a parasitic disease due to invasion of the Echinococcus multilocularis larva into the different tissues. The main host of this tape worms is Canidae family, especially foxes and jackals. Human beings are usually infected through eating contaminated vegetables and water with parasite eggs. In this article, one case of alveolar hydatid cyst has been reported in a 35 year-old woman

  18. Rare Lung Diseases II: Pulmonary Alveolar Proteinosis

    OpenAIRE

    Juvet, Stephen C; David Hwang; Waddell, Thomas K; Downey, Gregory P.

    2008-01-01

    The present article is the second in a series on rare lung diseases. It focuses on pulmonary alveolar proteinosis (PAP), a disorder in which lipoproteinaceous material accumulates in the alveolar space. PAP was first described in 1958, and for many years the nature of the material accumulating in the lungs was unknown. Major insights into PAP have been made in the past decade, and these have led to the notion that PAP is an autoimmume disorder in which autoantibodies interfere with signalling...

  19. A case report of pulmonary alveolar proteinosis

    OpenAIRE

    McDermott, Helen; Aitchison, Frances; Nathani, Nazim; Bhatnager, Anjali

    2009-01-01

    This is a case of pulmonary alveolar proteinosis that presented in an inner city hospital in Birmingham, UK. The patient was a previously well 42-year-old man, who went on to experience unusual cerebral complications of the disease. The presentation, imaging findings and diagnostic histology findings are described. Pulmonary alveolar proteinosis is a rare but important diagnosis. Characteristic high-resolution CT findings include diffuse ground glass density with superimposed interlobular sep...

  20. Toward Therapeutic Pulmonary Alveolar Regeneration in Humans

    OpenAIRE

    Massaro, Donald; Massaro, Gloria DeCarlo

    2006-01-01

    In humans, age results in loss of pulmonary alveoli; menopause accelerates loss of diffusing capacity, an index of alveolar surface area; and disease (e.g., chronic obstructive pulmonary disease) results in loss of alveoli. Thus, an important goal for investigators is to generate knowledge that allows induction of pulmonary alveolar regeneration in humans. Our enthusiasm for this goal and our assessment of its feasibility are based on work in several laboratories over the last decade that has...

  1. Remodeling of alveolar septa after murine pneumonectomy.

    Science.gov (United States)

    Ysasi, Alexandra B; Wagner, Willi L; Bennett, Robert D; Ackermann, Maximilian; Valenzuela, Cristian D; Belle, Janeil; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-06-15

    In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P > 0.05), but a significant decrease in the length of a subset of septal ends ("E"). Septal retraction, observed in 20-30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung (P surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling. PMID:26078396

  2. Particulate concentrations in pulmonary alveolar proteinosis

    Energy Technology Data Exchange (ETDEWEB)

    McEuen, D.D.; Abraham, J.L. (Univ. of California, San Diego, La Jolla (USA))

    1978-12-01

    Quantitative birefringent particle counts per 10 high-power fields in lung tissue were correlated with age, sex, and occupational exposure in 37 cases of pulmonary alveolar proteinosis. Counts were significantly higher in pulmonary alveolar proteinosis cases in both regions of alveolar proteinosis (47 {plus minus} 11) and perivascular and peribronchiolar areas (dust retention areas) (275 {plus minus} 65) than in 13 controls (5 {plus minus} 3 and 79 {plus minus} 23, respectively). Of a total of 8619 particles, 4817 were less than 1 micron, and 3771 were 1 to 10 microns in diameter. Fifty-nine percent were round, 19% fibrous, and 22% irregular. When analyzed individually, 20 of 37 cases (78%) had alveolar particle counts significantly higher than controls, and 10 of 26 cases had dust-retention area counts greater than controls (P less than 0.050). Known or possible occupational exposure was ascertained in 13 cases. In the remaining 24 cases insufficient occupational information was available. The mean age of the pulmonary alveolar proteinosis patients was 33 {plus minus} 4 years, and of the controls, 40 {plus minus} 7 years, and there was a male-to-female ratio of approximately 3:1. We propose that many cases of pulmonary alveolar proteinosis will ultimately be shown to be associated with environmental exposures to fine dusts or fumes.

  3. Macrophage Autophagy in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Maria Chiara Maiuri

    2013-01-01

    Full Text Available Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility.

  4. Insulin Influences Autophagy Response Distinctively in Macrophages of Different Compartments

    Directory of Open Access Journals (Sweden)

    Karen K. S. Sunahara

    2014-11-01

    Full Text Available Background/Aims: Diabetes mellitus (DM is characterized by hyperglycemia, associated to a lack or inefficiency of the insulin to regulate glucose metabolism. DM is also marked by alterations in a diversity of cellular processes that need to be further unraveled. In this study, we examined the autophagy pathway in diabetic rat macrophages before and after treatment with insulin. Methods: Bone marrow-derived macrophages (BMM, bronchoalveolar lavage (BAL and splenic tissue of diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., 10 days and control rats (physiological saline, i.v.. Some diabetic rats were given neutral protamine Hagedorn insulin (4 IU, s.c. 8 h before experiments. For characterization of the model and evaluation of the effect of insulin on the autophagic process, the following analyzes were performed: (a concentrations of cytokines: interleukin (IL-1β, tumor necrosis factor (TNF-α, IL-6, IL-4, IL-10, cytokine-induced neutrophil chemoattractant (CINC-1 and CINC-2 in the BAL supernatant was measured by ELISA; (b characterization of alveolar macrophage (AM of the BAL as surface antigens (MHCII, pan-macrophage KiM2R, CD11b and autophagic markers (protein microtubule-associated light chain (LC3, autophagy protein (Atg12 by flow cytometry and confocal microscopy (c study of macrophages differentiated from the bone marrow by flow cytometry and confocal microscopy (d histology of the spleen by immunohistochemistry associated with confocal microscopy. Results: Interestingly, insulin exerted antagonistic effects on macrophages from different tissues. Macrophages from bronchoalveolar lavage (BAL enhanced their LC3 autophagosome bound content after treatment with insulin whereas splenic macrophages from red pulp in diabetic rats failed to enhance their Atg 12 levels compared to control animals. Insulin treatment in diabetic rats did not change LC3 content in bone marrow derived macrophages (BMM. M1 and M2 macrophages behaved accordingly to the

  5. A novel real time imaging platform to quantify macrophage phagocytosis.

    Science.gov (United States)

    Kapellos, Theodore S; Taylor, Lewis; Lee, Heyne; Cowley, Sally A; James, William S; Iqbal, Asif J; Greaves, David R

    2016-09-15

    Phagocytosis of pathogens, apoptotic cells and debris is a key feature of macrophage function in host defense and tissue homeostasis. Quantification of macrophage phagocytosis in vitro has traditionally been technically challenging. Here we report the optimization and validation of the IncuCyte ZOOM® real time imaging platform for macrophage phagocytosis based on pHrodo® pathogen bioparticles, which only fluoresce when localized in the acidic environment of the phagolysosome. Image analysis and fluorescence quantification were performed with the automated IncuCyte™ Basic Software. Titration of the bioparticle number showed that the system is more sensitive than a spectrofluorometer, as it can detect phagocytosis when using 20× less E. coli bioparticles. We exemplified the power of this real time imaging platform by studying phagocytosis of murine alveolar, bone marrow and peritoneal macrophages. We further demonstrate the ability of this platform to study modulation of the phagocytic process, as pharmacological inhibitors of phagocytosis suppressed bioparticle uptake in a concentration-dependent manner, whereas opsonins augmented phagocytosis. We also investigated the effects of macrophage polarization on E. coli phagocytosis. Bone marrow-derived macrophage (BMDM) priming with M2 stimuli, such as IL-4 and IL-10 resulted in higher engulfment of bioparticles in comparison with M1 polarization. Moreover, we demonstrated that tolerization of BMDMs with lipopolysaccharide (LPS) results in impaired E. coli bioparticle phagocytosis. This novel real time assay will enable researchers to quantify macrophage phagocytosis with a higher degree of accuracy and sensitivity and will allow investigation of limited populations of primary phagocytes in vitro. PMID:27475716

  6. Perawatan Ortodontik Gigi Anterior Berjejal dengan Tulang Alveolar yang Tipis

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    Miesje K. Purwanegara

    2015-09-01

    Full Text Available Anterior teeth movement in orthodontic treatment is limited to labiolingual direction by very thin alveolar bone. An uncontrolled anterior tooth movement to labiolingual direction can cause alveolar bone perforation at its root segment. This case report is to remind us that alveolar bone thickness limits orthodontc tooth movement. A case of crowded anterior teeth with thin alveolar bone in malocclusion I is reported. This case is treated using adgewise orthodontic appliance. Protraction of anterior teeth is anticipated due to thin alveolar bone on the anterior surface. The conclusion is although the alveolar bone surrounding the crowded anterior teeth is thin, by controlling the movement the teeth reposition is allowed.

  7. Glutamine Modulates Macrophage Lipotoxicity

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    Li He

    2016-04-01

    Full Text Available Obesity and diabetes are associated with excessive inflammation and impaired wound healing. Increasing evidence suggests that macrophage dysfunction is responsible for these inflammatory defects. In the setting of excess nutrients, particularly dietary saturated fatty acids (SFAs, activated macrophages develop lysosome dysfunction, which triggers activation of the NLRP3 inflammasome and cell death. The molecular pathways that connect lipid stress to lysosome pathology are not well understood, but may represent a viable target for therapy. Glutamine uptake is increased in activated macrophages leading us to hypothesize that in the context of excess lipids glutamine metabolism could overwhelm the mitochondria and promote the accumulation of toxic metabolites. To investigate this question we assessed macrophage lipotoxicity in the absence of glutamine using LPS-activated peritoneal macrophages exposed to the SFA palmitate. We found that glutamine deficiency reduced lipid induced lysosome dysfunction, inflammasome activation, and cell death. Under glutamine deficient conditions mTOR activation was decreased and autophagy was enhanced; however, autophagy was dispensable for the rescue phenotype. Rather, glutamine deficiency prevented the suppressive effect of the SFA palmitate on mitochondrial respiration and this phenotype was associated with protection from macrophage cell death. Together, these findings reveal that crosstalk between activation-induced metabolic reprogramming and the nutrient microenvironment can dramatically alter macrophage responses to inflammatory stimuli.

  8. Pulmonary alveolar proteinosis with myeloproliferative syndrome with myelodysplasia: bronchoalveolar lavage reduces white blood cell count.

    Science.gov (United States)

    Pollack, Seth M; Gutierrez, Guillermo; Ascensao, Joao

    2006-08-01

    Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by surfactant component accumulation in the alveolar space. Primary PAP is likely an autoimmune disorder caused by antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF). When an underlying disease causes PAP, this is called secondary PAP. Hematologic malignancies are an important cause of secondary PAP. As the pathogenesis of primary PAP has become more fully understood, improvements in diagnostic and therapeutic approaches have followed. However, when PAP is secondary to an underlying hematologic malignancy, much remains unclear. Here we describe for the first time a patient with hybrid myelodysplastic syndrome/myeloproliferative syndrome and PAP who had a marked decrease in her white blood cell count following a transbronchial biopsy accompanied by bronchoalveolar lavage (BAL). Similar significant decreases in WBC count accompanied clinical improvement following two unilateral BALs. Given that patients with pulmonary alveolar proteinosis frequently have elevated GM-CSF in bronchoalveolar fluid, this observation provides a unique vantage point to understand the pathophysiology of secondary PAP. PMID:16906593

  9. Dendritic cell and macrophage staining by monoclonal antibodies in tissue sections and epidermal sheets.

    OpenAIRE

    Flotte, T. J.; Springer, T A; Thorbecke, G. J.

    1983-01-01

    Mouse tissue sections were stained by monoclonal antibodies to macrophage antigens (Mac-1 (M1/70), Mac-2 (M3/38), Mac-3 (M3/84) with the use of immunoperoxidase. Mac-1 was located diffusely in the cytoplasm of round cells in a high percentage of alveolar macrophages, resident peritoneal and bone marrow cells, in splenic red pulp, and in rare perivascular cells in the thymus. Mac-1 was absent in epithelial cells and Langerhans cells. Mac-2 was strongly positive in many dendritic cells in the t...

  10. Nuclear study of Melusine; Etude nucleaire de Melusine

    Energy Technology Data Exchange (ETDEWEB)

    Cherot, J. [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1959-07-01

    In this report are reviewed - with respect to starting of experiments - the main nuclear characteristics of a 20 per cent enriched uranium lattice, with light water as moderator and reflector. The reactor is to operate at 1 MW. 1) Study of various critical masses. 2) Control. Effectiveness of cadmium. Control rods and of a stainless steel regulating rod. 3) Study of the effect on reactivity of disturbances in the core center. 4) Study of xenon and samarium poisoning. 5) Temperature factor. 6) Heat exchanges in a fuel element. (author) [French] On etudie, dans ce rapport, les principales proprietes nucleaires d'un reseau a uranium enrichi (20 pour cent), dont le moderateur et le reflecteur sont l'eau legere en vue des experiences de demarrage. Ce reacteur devra fonctionner a 1 MW. 1) Etude de diverses masses critiques. 2) Controle. Efficacite des barres de controle en cadmium et d'une barre de reglage en acier inoxydable. 3) Etude de l'effet sur la reactivite de perturbation au centre du coeur. 4) Etude de l'empoisonnement xenon et samarium. 5) Coefficient de temperature. 6) Echanges thermiques dans un element. (auteur)

  11. Lateralization Technique and Inferior Alveolar Nerve Transposition

    Directory of Open Access Journals (Sweden)

    Angélica Castro Pimentel

    2016-01-01

    Full Text Available Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics.

  12. Lateralization Technique and Inferior Alveolar Nerve Transposition

    Science.gov (United States)

    Sanches, Marco Antonio; Ramalho, Gabriel Cardoso; Manzi, Marcello Roberto

    2016-01-01

    Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics. PMID:27433360

  13. Whole lung lavage for pulmonary alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    Jayaraman S

    2010-01-01

    Full Text Available A 26-year-old male presented with complaints of dry cough of six months and progressive breathlessness of three months duration. He was coughing out milky white sputum for two months and had lost 12 kg weight in two months. He had an evening rise in temperature of one month duration. Clinically, the patient was in respiratory distress and the respiratory system examination revealed bilateral velcro crackles. High resolution computed tomography chest showed bilateral diffuse reticulonodular opacities and "Crazy Paving" pattern suggestive of alveolar proteinosis. Broncho alveolar lavage showed eosinophilic granular material, which was periodic acid-Schiff positive. Open lung biopsy was done to confirm the diagnosis and the histopathologic examination revealed eosinophilic secretions with granular appearance suggestive of pulmonary alveolar proteinosis. Subsequently, patient underwent bilateral sequential whole lung lavage under general anesthesia. Patient showed marked clinical and radiological improvement after sequential whole lung lavage.

  14. A plasmapheresis protocol for refractory pulmonary alveolar proteinosis.

    Science.gov (United States)

    Garber, Bryan; Albores, Jeffrey; Wang, Tisha; Neville, Thanh H

    2015-04-01

    Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of proteinaceous material within the lungs. While typically managed with whole lung lavage (WLL), more recent PAP therapies aimed at reducing granulocyte-macrophage colony stimulating factor autoantibodies (anti-GM-CSF) have reduced symptoms and improved lung function. We present a patient with PAP refractory to WLL, exogenous GM-CSF and rituximab who underwent a novel plasmapheresis protocol as a therapeutic trial. While previously reported regimens have utilized plasmapheresis sessions distributed over months, our patient underwent five consecutive days of plasmapheresis, followed by rituximab. Anti-GM-CSF levels decreased from 24.8 to 2.7 mcg/mL post-plasmapheresis. This reduction of autoantibody correlated with reduction in WLL frequency, increase in diffusing capacity for carbon monoxide, and subjective improvement in dyspnea. Our case suggests that five consecutive days of plasmapharesis results in increased clearance of anti-GM-CSF and may be potentially efficacious in cases of refractory PAP. PMID:25557091

  15. Alveolar proteinosis: case report and literature review

    Directory of Open Access Journals (Sweden)

    2013-07-01

    Full Text Available Alveolar proteinosis is a rare disease. Its etiology, pathology, and manifestations are becoming increasingly more apparent. Few cases have been reported, which highlights the importance of reporting this case and reviewing current literature. New therapeutic options are being introduced with adequate outcomes thereby making it possible to manage patients who were previously unresponsive to conventional treatment. 25% of cases resolve spontaneously, while most patients require conventional treatment with total lung lavage that often does not improve prognosis. The case reported in this article was associated to Mycobacterium tuberculosis infection and diabetes. Primary alveolar proteinosis can have a direct relationship to these concomitant conditions.

  16. Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance

    OpenAIRE

    Soroosh, Pejman; Doherty, Taylor A.; Duan, Wei; Mehta, Amit Kumar; Choi, Heonsik; Adams, Yan Fei; Mikulski, Zbigniew; Khorram, Naseem; Rosenthal, Peter; Broide, David H.; Croft, Michael

    2013-01-01

    Airway tolerance is the usual outcome of inhalation of harmless antigens. Although T cell deletion and anergy are likely components of tolerogenic mechanisms in the lung, increasing evidence indicates that antigen-specific regulatory T cells (inducible Treg cells [iTreg cells]) that express Foxp3 are also critical. Several lung antigen-presenting cells have been suggested to contribute to tolerance, including alveolar macrophages (MØs), classical dendritic cells (DCs), and plasmacytoid DCs, b...

  17. Tissue-specific induction of ADAMTS2 in monocytes and macrophages by glucocorticoids.

    OpenAIRE

    Hofer, Thomas P. J.; Frankenberger, Marion; Mages, Jorg; Lang, Roland; Meyer, Peter; Hoffmann, Reinhard; Colige, Alain; Ziegler-Heitbrock, Loms

    2008-01-01

    The regulated expression of ADAMTS2 (a disintegrin and metalloproteinase with thrombospondin motifs), a secreted metalloproteinase involved in the processing of procollagen to collagen, was studied in peripheral blood mononuclear cells (PBMC). Stimulation with glucocorticoids (GC) resulted in a pronounced dose- and time-dependent increase of ADAMTS2 mRNA levels in PBMC. The increase of ADAMTS2 expression was specific for CD14++ monocytes (440-fold) and alveolar macrophages (200-fold), whereas...

  18. Biofilm-derived Legionella pneumophila evades the innate immune response in macrophages

    OpenAIRE

    Arwa eAbu Khweek; Natalia eFernández Dávila; Kyle eCaution; Anwari eAkhter; Basant eAbdulrahman; Mia eTazi; Hoda eHassan; Laura eNovotny; Lauren eBakaletz; Amer, Amal O.

    2013-01-01

    Legionella pneumophila, the causative agent of Legionnaire’s disease, replicates in human alveolar macrophages to establish infection. There is no human-to-human transmission and the main source of infection is L. pneumophila biofilms established in air conditioners, water fountains, and hospital equipments. The biofilm structure provides protection to the organism from disinfectants and antibacterial agents. L. pneumophila infection in humans is characterized by a subtle initial immune respo...

  19. Biofilm-derived Legionella pneumophila evades the innate immune response in macrophages

    OpenAIRE

    Abu Khweek, Arwa; Fernández Dávila, Natalia S.; Caution, Kyle; Akhter, Anwari; Abdulrahman, Basant A.; Tazi, Mia; Hassan, Hoda; Novotny, Laura A.; Bakaletz, Lauren O.; Amer, Amal O.

    2013-01-01

    Legionella pneumophila, the causative agent of Legionnaire's disease, replicates in human alveolar macrophages to establish infection. There is no human-to-human transmission and the main source of infection is L. pneumophila biofilms established in air conditioners, water fountains, and hospital equipments. The biofilm structure provides protection to the organism from disinfectants and antibacterial agents. L. pneumophila infection in humans is characterized by a subtle initial immune respo...

  20. The elusive antifibrotic macrophage

    Directory of Open Access Journals (Sweden)

    Adhyatmika eAdhyatmika

    2015-11-01

    Full Text Available Fibrotic diseases, especially of the liver, the cardiovascular system, the kidneys, and the lungs account for approximately 45% of deaths in Western societies. Fibrosis is a serious complication associated with aging and/or chronic inflammation or injury and cannot be treated effectively yet. It is characterized by excessive deposition of extracellular matrix (ECM proteins by myofibroblasts and impaired degradation by macrophages. This ultimately destroys the normal structure of an organ, which leads to loss of function. Most efforts to develop drugs have focused on inhibiting ECM production by myofibroblasts and have not yielded many effective drugs yet. Another option is to stimulate the cells that are responsible for degradation and uptake of excess ECM, i.e. antifibrotic macrophages. However, macrophages are plastic cells that have many faces in fibrosis, including profibrotic behaviour stimulating ECM production. This can be dependent on their origin, as the different organs have tissue-resident macrophages with different origins and a various influx of incoming monocytes in steady-state conditions and during fibrosis. To be able to pharmacologically stimulate the right kind of behaviour in fibrosis, a thorough characterization of antifibrotic macrophages is necessary, as well as an understanding of the signals they need to degrade ECM. In this review we will summarize the current state of the art regarding the antifibrotic macrophage phenotype and the signals that stimulate its behaviour.

  1. Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice

    DEFF Research Database (Denmark)

    Jung, A; Allen, L; Nyengaard, Jens Randel;

    2005-01-01

    (-)D(-) mice have fewer and larger alveoli, an increase in the number and size of type II cells, as well as more numerous and larger alveolar macrophages. More surfactant-storing lamellar bodies are seen in type II cells, leading to a threefold increase in the total volume of lamellar bodies per lung, but the......Alveolar epithelial type II cells synthesize and secrete surfactant. The surfactant-associated proteins A and D (SP-A and SP-D), members of the collectin protein family, participate in pulmonary immune defense, modulation of inflammation, and surfactant metabolism. Both proteins are known to have...... overlapping as well as distinct functions. The present study provides a design-based stereological analysis of adult mice deficient in both SP-A and SP-D (A(-)D(-)) with special emphasis on parameters characterizing alveolar architecture and surfactant-producing type II cells. Compared to wild-type, A...

  2. Quantitation and renewal of alveolar and bronchiolar cell populations of rat lungs. Changes during some pathological processes

    International Nuclear Information System (INIS)

    The various cells of alveolar and bronchiolar tissues of rat lungs were studied qualitatively and quantitatively. In physiological conditions, the renewal rate of the cell populations is low and the frequency of the various cell types is constant. This stability, especially at the level of the alveolar tissue, was also found during the latency period and the development of radiation-induced lung cancers. A particular cellular population was demonstrated: marginated leukocyte pool at the level of the pulmonary circulation. This pool was different both qualitatively and quantitatively from the leukocytes of the systemic circulation and, in physiological conditions, behaved as a cellular reservoir of monocytes chiefly re-distributed according to the body needs. In pathological conditions, its fast migration contributed to the defence of the alveolar medium. A quantitative study of the renewal of alveolar macrophages showed that under 1 p. cent of the marginated leukocyte pool is used daily to keep up this population. This fraction undergoes a maturation stage by cellular division within the endoalveolar medium. In some pathological conditions, this division can be completely inhibited

  3. Bone Marrow Mesenchymal Stem Cells Inhibit Lipopolysaccharide-Induced Inflammatory Reactions in Macrophages and Endothelial Cells

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    Dequan Li

    2016-01-01

    Full Text Available Background. Systemic inflammatory response syndrome (SIRS accompanied by trauma can lead to multiple organ dysfunction syndrome (MODS and even death. Early inhibition of the inflammation is necessary for damage control. Bone marrow mesenchymal stem cells (BMSCs, as a novel therapy modality, have been shown to reduce inflammatory responses in human and animal models. Methods. In this study, we used Western blot, quantitative PCR, and enzyme-linked immunosorbent assay (ELISA to assess the activity of BMSCs to suppress the inflammation induced by lipopolysaccharide (LPS in human umbilical cord endothelial cells (HUVECs and alveolar macrophages. Results. Our results demonstrated that LPS caused an inflammatory response in alveolar macrophages and HUVECs, increased permeability of HUVEC, upregulated expression of toll-like receptor (TLR 2, TLR4, phosphorylated p65, downregulated release of IL10, and promoted release of TNF-α in both cells. Coculture with BMSCs attenuated all of these activities induced by LPS in the two tested cell types. Conclusions. Together, our results demonstrate that BMSCs dosage dependently attenuates the inflammation damage of alveolar macrophages and HUVECs induced by LPS.

  4. Complex determinants of macrophage tropism in env of simian immunodeficiency virus.

    Science.gov (United States)

    Mori, K; Ringler, D J; Kodama, T; Desrosiers, R C

    1992-04-01

    Macrophage-tropic virus variants evolved during the course of infection of individual rhesus monkeys with cloned, non-macrophagetropic simian immunodeficiency virus. Specific changes in the envelope gene (env) were found to be primarily responsible for the dramatic increase in the ability of the virus to replicate in macrophages. Cloned viruses differing at nine amino acid positions in env exhibited a more than 100-fold difference in replicative capacity for primary cultures of rhesus monkey alveolar macrophages. At least five of the nine amino acid changes contributed to macrophage tropism. These determinants were distributed across the full length of env, including both the gp120 and gp41 products of the env gene. Furthermore, the emergence of macrophagetropic variants in vivo was associated with specific pathologic manifestations in which the macrophage is the major infected cell type. Thus, major determinants of macrophage tropism reside in env, they can be complex in nature, and the presence of macrophage-tropic virus variants in vivo can influence the disease course and disease manifestations.

  5. Selective alveolar corticotomy to intrude overerupted molars.

    Science.gov (United States)

    Oliveira, Dauro Douglas; de Oliveira, Bruno Franco; de Araújo Brito, Helio Henrique; de Souza, Margareth Maria Gomes; Medeiros, Paulo José

    2008-06-01

    Orthodontic intrusion of overerupted molars in adults is challenging for most clinicians. Efficient intrusion can be achieved by combining selective alveolar corticotomies with a modified full-coverage maxillary splint to reduce surgical risks, treatment time, and costs for both orthodontists and patients. PMID:18538256

  6. Iatrogenic injury to the inferior alveolar nerve

    DEFF Research Database (Denmark)

    Hillerup, Søren

    2008-01-01

    The purpose of this prospective, non-randomised, descriptive study is to characterise the neurosensory deficit and associated neurogenic discomfort in 52 patients with iatrogenic injury to the inferior alveolar nerve (IAN). All patients were examined and followed up according to a protocol...

  7. Elevated CO2 selectively inhibits interleukin-6 and tumor necrosis factor expression and decreases phagocytosis in the macrophage.

    Science.gov (United States)

    Wang, Naizhen; Gates, Khalilah L; Trejo, Humberto; Favoreto, Silvio; Schleimer, Robert P; Sznajder, Jacob I; Beitel, Greg J; Sporn, Peter H S

    2010-07-01

    Elevated blood and tissue CO(2), or hypercapnia, is common in severe lung disease. Patients with hypercapnia often develop lung infections and have an increased risk of death following pneumonia. To explore whether hypercapnia interferes with host defense, we studied the effects of elevated P(CO2) on macrophage innate immune responses. In differentiated human THP-1 macrophages and human and mouse alveolar macrophages stimulated with lipopolysaccharide (LPS) and other Toll-like receptor ligands, hypercapnia inhibited expression of tumor necrosis factor and interleukin (IL)-6, nuclear factor (NF)-kappaB-dependent cytokines critical for antimicrobial host defense. Inhibition of IL-6 expression by hypercapnia was concentration dependent, rapid, reversible, and independent of extracellular and intracellular acidosis. In contrast, hypercapnia did not down-regulate IL-10 or interferon-beta, which do not require NF-kappaB. Notably, hypercapnia did not affect LPS-induced degradation of IkappaB alpha, nuclear translocation of RelA/p65, or activation of mitogen-activated protein kinases, but it did block IL-6 promoter-driven luciferase activity in mouse RAW 264.7 macrophages. Elevated P(CO2) also decreased phagocytosis of opsonized polystyrene beads and heat-killed bacteria in THP-1 and human alveolar macrophages. By interfering with essential innate immune functions in the macrophage, hypercapnia may cause a previously unrecognized defect in resistance to pulmonary infection in patients with advanced lung disease. PMID:20181940

  8. Rat lung macrophage tumor cytotoxin production: impairment by chronic in vivo cigarette smoke exposure.

    Science.gov (United States)

    Flick, D A; Gonzalez-Rothi, R J; Harris, J O; Gifford, G E

    1985-11-01

    Macrophages in the presence of bacteria-derived lipopolysaccharide (LPS) stimuli produce a soluble cytotoxin which is toxic to tumor cells. In this study, we examined various parameters of cytotoxin production from pulmonary lavage cells obtained from Fisher 344 cesarean-derived rats. Cultures of macrophages were derived from pulmonary lavage cells and stimulated in vitro with LPS. Cytotoxin production was assayed in vitro using an L-929 cell target assay. Pulmonary lavage preparations contained a relatively pure population of macrophages, and adherence studies revealed that nonadherent lavage cells contributed negligible amounts of cytotoxin, indicating that macrophages were responsible for cytotoxin production. After LPS stimulation, cytotoxin production became maximal within 10 h and thereafter plateaued. Doses of LPS above 0.1 microgram/ml were optimal for production, and in the absence of LPS, no cytotoxin was detected. Because cigarette smoke is the major etiological factor in the development of lung cancers and because smoking is known to profoundly alter the function of alveolar macrophages in humans and experimental animals, subsequent experiments examined the role of chronic cigarette smoke exposure on tumoricidal activity of lung macrophages. Rats were exposed in vivo for 8 wk to either cigarette smoke or air (sham-treated controls). When lavage cells were cultured and stimulated with LPS (1 microgram/ml), 5- to 10-fold less cytotoxin was produced by lavage cells from rats exposed to cigarette smoke. Similarly, using a direct cytotoxicity assay, lung macrophages of smoke-exposed animals also revealed marked impairment in cytotoxicity against L-929 cell targets, and this was noted over a wide range of macrophage:tumor target cell ratios. Another product of macrophages, interferon, was also decreased in rats exposed in vivo to cigarette smoke when compared to sham-treated controls. These results suggest that cigarette smoke exposure may impair pulmonary

  9. Macrophage derived chemokine (CCL22, thymus and activation-regulated chemokine (CCL17, and CCR4 in idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Yamaguchi Kazuhiro

    2009-08-01

    Full Text Available Abstract Background Idiopathic pulmonary fibrosis (IPF is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation of the macrophage-derived chemokine CCL22 and the thymus activation-regulated chemokine CCL17 among chemokines, in a rat model of radiation pneumonitis/pulmonary fibrosis and preliminarily observed an increase in bronchoalveolar (BAL fluid CCL22 levels of IPF patients. Methods We examined the expression of CCR4, a specific receptor for CCL22 and CCL17, in bronchoalveolar lavage (BAL fluid cells, as well as the levels of CCL22 and CCL17, to elucidate their pathophysiological roles in pulmonary fibrosis. We also studied their immunohistochemical localization. Results BAL fluid CCL22 and CCL17 levels were significantly higher in patients with IPF than those with collagen vascular diseases and healthy volunteers, and there was a significant correlation between the levels of CCL22 and CCL17 in patients with IPF. CCL22 levels in the BAL fluid did not correlate with the total cell numbers, alveolar lymphocytes, or macrophages in BAL fluid. However, the CCL22 levels significantly correlated with the numbers of CCR4-expressing alveolar macrophages. By immunohistochemical and immunofluorescence analysis, localization of CCL22 and CCR4 to CD68-positive alveolar macrophages as well as that of CCL17 to hyperplastic epithelial cells were shown. Clinically, CCL22 BAL fluid levels inversely correlated with DLco/VA values in IPF patients. Conclusion We speculated that locally overexpressed CCL22 may induce lung dysfunction through recruitment and activation of CCR4-positive alveolar macrophages.

  10. Pulmonary alveolar proteinosis and aluminum dust exposure

    Energy Technology Data Exchange (ETDEWEB)

    Miller, R.R.; Churg, A.M.; Hutcheon, M.; Lom, S.

    1984-08-01

    A 44-yr-old male presented shortness of breath, diffuse X-ray infiltrates, and physiologic evidence of a restrictive lung disease. Biopsy revealed pulmonary alveolar proteinosis. The patient had worked for the previous 6 yr as an aluminum rail grinder in a very dusty environment. Analysis of his lung tissue revealed greater than 300 X 10(6) particles of aluminum/g dry lung; all of the particles appeared as spheres of less than 1 mu diameter. We believe that this case represents an example of pulmonary alveolar proteinosis induced by inhalation of aluminum particles; this finding confirms animal studies which suggest that proteinosis can be produced by very large doses of many types of finely divided mineral dust.

  11. Silver Nanoparticles in Alveolar Bone Surgery Devices

    Directory of Open Access Journals (Sweden)

    Stefano Sivolella

    2012-01-01

    Full Text Available Silver (Ag ions have well-known antimicrobial properties and have been applied as nanostrategies in many medical and surgical fields, including dentistry. The use of silver nanoparticles (Ag NPs may be an option for reducing bacterial adhesion to dental implant surfaces and preventing biofilm formation, containing the risk of peri-implant infections. Modifying the structure or surface of bone grafts and membranes with Ag NPs may also prevent the risk of contamination and infection that are common when alveolar bone augmentation techniques are used. On the other hand, Ag NPs have revealed some toxic effects on cells in vitro and in vivo in animal studies. In this setting, the aim of the present paper is to summarize the principle behind Ag NP-based devices and their clinical applications in alveolar bone and dental implant surgery.

  12. Bilateral stony lung: pulmonary alveolar microlithiasis.

    Science.gov (United States)

    Chandra, Subhash; Mohan, Anant; Guleria, Randeep; Das, Prasenjit; Sarkar, Chitra

    2009-01-01

    A 40-year-old male paddy field worker was referred for exertional shortness of breath and non-productive cough for 4 years. He had been treated for pulmonary tuberculosis twice. Chest radiograph showed extensive bilateral nodular opacities ("sandstorm-like") in the middle and lower lobe. Pulmonary function tests revealed a restrictive ventilatory defect. High resolution CT showed widespread nodular infiltration with "crazy paving" appearance and interrupted black pleura sign. This was confirmed as pulmonary alveolar microlithiasis (PAM) by trans-bronchial lung biopsy, which showed normal respiratory lining epithelium with dilated alveolar spaces containing many calcific bodies, some of which showed concentric calcification. The possibilities of silicosis (due to exposure to husk) and tuberculosis, both of which can mimic PAM clinically and radiologically, made this case a diagnostic challenge. PMID:21686505

  13. Bmp2 and Bmp4 accelerate alveolar bone development.

    Science.gov (United States)

    Ou, Mingming; Zhao, Yibing; Zhang, Fangming; Huang, Xiaofeng

    2015-06-01

    Alveolar bone remodeling is a continuous process that takes place during development and in response to various physiological and pathological stimuli. However, detailed knowledge regarding the underlying mechanisms involved in alveolar bone development is still lacking. This study aims at improving our understanding of alveolar bone formation and the role of bone morphogenetic proteins (Bmps) in this process. Mice at embryonic (E) day 13.5 to postnatal (PN) day 15.5 were selected to observe the process of alveolar bone development. Alveolar bone development was found to be morphologically observable at E14.5. Molar teeth isolated from mice at PN7.5 were pretreated with Bmp2, Bmp4, Noggin, or BSA, and grafted subcutaneously into mice. The subcutaneously implanted tooth germs formed alveolar bone indicating the role of the dental follicle in alveolar bone development. Alveolar bone formation was increased after pretreatment with Bmp2 and Bmp4, but not with Noggin. Gene expression levels in dental follicle cells from murine molars were also determined by real-time RT-PCR. The expression levels of Runx2, Bsp, and Ocn were significantly higher in dental follicle cells cultured with Bmp2 or Bmp4, and significantly lower in those cultured with Noggin when compared with that of the BSA controls. Our results suggest that the dental follicle participates in alveolar bone formation and Bmp2/4 appears to accelerate alveolar bone development.

  14. [Development of drug delivery systems for targeting to macrophages].

    Science.gov (United States)

    Chono, Sumio

    2007-09-01

    Drug delivery systems (DDS) using liposomes as drug carriers for targeting to macrophages have been developed for the treatment of diseases that macrophages are related to their progress. Initially, DDS for the treatment of atherosclerosis are described. The influence of particle size on the drug delivery to atherosclerotic lesions that macrophages are richly present and antiatherosclerotic effects following intravenous administration of liposomes containing dexamethasone (DXM-liposomes) was investigated in atherogenic mice. Both the drug delivery efficacy of DXM-liposomes (particle size, 200 nm) to atherosclerotic lesions and their antiatherosclerotic effects were greater than those of 70 and 500 nm. These results indicate that there is an optimal particle size for drug delivery to atherosclerotic lesions. DDS for the treatment of respiratory infections are then described. The influence of particle size and surface mannosylation on the drug delivery to alveolar macrophages (AMs) and antibacterial effects following pulmonary administration of liposomes containing ciprofloxacin (CPFX-liposomes) was investigated in rats. The drug delivery efficacy of CPFX-liposomes to AMs was particle size-dependent over the range 100-1000 nm and then became constant at over 1000 nm. These results indicate that the most effective size is 1000 nm. Both the drug delivery efficacy of mannosylated CPFX-liposomes (particle size, 1000 nm) to AMs and their antibacterial effects were significantly greater than those of unmodified CPFX-liposomes. These results indicate that the surface mannosylation is useful method for drug delivery to AMs. This review provides useful information to help in the development of novel pharmaceutical formulations aimed at drug targeting to macrophages.

  15. Alveolar ridge augmentation by osteoinduction in rats

    DEFF Research Database (Denmark)

    Pinholt, E M; Bang, G; Haanaes, H R

    1990-01-01

    The purpose of this study was to evaluate bone substitutes for alveolar ridge augmentation by osteoinduction. Allogenic, demineralized, and lyophilized dentin and bone was tested for osteoinductive properties in order to establish an experimental model for further studies. Implantations were...... performed subperiosteally on the premaxilla and heterotopically in the abdominal muscles of rats. Light microscopic evaluations revealed that all allogenic, demineralized, and lyophilized dentin and bone implants induced new bone formation. No inflammatory or foreign body reactions were observed....

  16. Wormhole Travel for Macrophages.

    Science.gov (United States)

    Okabe, Yasutaka; Medzhitov, Ruslan

    2016-04-21

    Leukocyte recruitment is generally achieved by rapid migration of inflammatory cells out of circulation, through modified blood vessels, and into affected tissues. Now, Wang and Kubes show that macrophages can be rapidly recruited from body cavities to the liver, via a non-vascular route, where they help to coordinate tissue repair. PMID:27104973

  17. Extensive macrophage accumulation in young and old Niemann-Pick C1 model mice involves the alternative, M2, activation pathway and inhibition of macrophage apoptosis.

    Science.gov (United States)

    Deutsch, Gail; Muralidhar, Akshay; Le, Ellen; Borbon, Ivan A; Erickson, Robert P

    2016-03-10

    We have studied the pathophysiology of lung disease which occurs in two mouse models of Niemann-Pick C1 disease. We utilized Npc1(-/-) mice transgenic for normal gene expression in glia or neurons and glia at ages several fold the usual and a mouse model of the juvenile form of NPC1, a point mutation, at one age to confirm some findings. Lung weights, as per cent of body weight, increase much more than liver and spleen weights. Although pulmonary function parameters only vary for hysteresis between young and older Npc1(-/-) mice, they are markedly different than those found in normal control mice. Cholesterol accumulation continued in the older mice but sphingosine-1-phosphate was not increased. Bronchoalveolar lavage (BAL) showed a massive increase (26×) in the number of macrophages. Histologic examination from the older, transgenic Npc1(-/-) mice showed small foci of alveolar proteinosis and evidence of hemorrhage, as well as dense macrophage accumulation. A large subset of macrophages was immunopositive for Fizz1 or arginase-1, markers of the alternative activation pathway, while no Fizz1 or arginase-1 positive macrophages were found in wild-type mice. The percentage of marker positive macrophages was relatively stable at 5-10% at various ages and within the 2 transgenic models. Phosphohistone H3 and Ki67 showed low levels of proliferation of these macrophages. Apoptosis was prominent within lung capillary endothelial cells, but limited within macrophages. Thus, activation of the alternative pathway is involved in Niemann-Pick C1 associated pulmonary macrophage accumulation, with low proliferation of these cells balanced by low levels of apoptosis. PMID:26707209

  18. In situ methods for assessing alveolar mechanics.

    Science.gov (United States)

    Wu, You; Perlman, Carrie E

    2012-02-01

    Lung mechanics are an important determinant of physiological and pathophysiological lung function. Recent light microscopy studies of the intact lung have furthered the understanding of lung mechanics but used methodologies that may have introduced artifacts. To address this concern, we employed a short working distance water immersion objective to capture confocal images of a fluorescently labeled alveolar field on the costal surface of the isolated, perfused rat lung. Surface tension held a saline drop between the objective tip and the lung surface, such that the lung surface was unconstrained. For comparison, we also imaged with O-ring and coverslip; with O-ring, coverslip, and vacuum pressure; and without perfusion. Under each condition, we ventilated the lung and imaged the same region at the endpoints of ventilation. We found use of a coverslip caused a minimal enlargement of the alveolar field; additional use of vacuum pressure caused no further dimensional change; and absence of perfusion did not affect alveolar field dimension. Inflation-induced expansion was unaltered by methodology. In response to inflation, percent expansion was the same as recorded by all four alternative methods. PMID:22074721

  19. Inhibition of nuclear factor-kappa B activation decreases survival of Mycobacterium tuberculosis in human macrophages.

    Directory of Open Access Journals (Sweden)

    Xiyuan Bai

    Full Text Available Nuclear factor-kappa B (NFκB is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NFκB are more likely to succumb to Mycobacterium tuberculosis (MTB. However, the role of NFκB in host defense in humans is not fully understood. We sought to examine the role of NFκB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NFκB activation using BAY 11-7082 (BAY, an inhibitor of IκBα kinase or an adenovirus construct with a dominant-negative IκBα significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NFκB inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NFκB inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy.

  20. Biofilm-derived Legionella pneumophila evades the innate immune response in macrophages

    Directory of Open Access Journals (Sweden)

    Arwa eAbu Khweek

    2013-05-01

    Full Text Available Legionella pneumophila, the causative agent of Legionnaire’s disease, replicates in human alveolar macrophages to establish infection. There is no human-to-human transmission and the main source of infection is L. pneumophila biofilms established in air conditioners, water fountains, and hospital equipments. The biofilm structure provides protection to the organism from disinfectants and antibacterial agents. L. pneumophila infection in humans is characterized by a subtle initial immune response, giving time for the organism to establish infection before the patient succumbs to pneumonia. Planktonic L. pneumophila elicits a strong immune response in murine, but not in human macrophages enabling control of the infection. Interactions between planktonic L. pneumophila and murine or human macrophages have been studied for years, yet the interface between biofilm-derived L. pneumophila and macrophages has not been explored. Here, we demonstrate that biofilm-derived L. pneumophila replicates significantly more in murine macrophages than planktonic bacteria. In contrast to planktonic L. pneumophila, biofilm-derived L. pneumophila lacks flagellin expression, do not activate caspase-1 or 7 and trigger less cell death. In addition, while planktonic L. pneumophila is promptly delivered to lysosomes for degradation, most biofilm-derived bacteria were enclosed in a vacuole that did not fuse with lysosomes in murine macrophages. This study advances our understanding of the innate immune response to biofilm-derived L. pneumophila and closely reproduces the natural mode of infection in human.

  1. Biofilm-derived Legionella pneumophila evades the innate immune response in macrophages.

    Science.gov (United States)

    Abu Khweek, Arwa; Fernández Dávila, Natalia S; Caution, Kyle; Akhter, Anwari; Abdulrahman, Basant A; Tazi, Mia; Hassan, Hoda; Novotny, Laura A; Bakaletz, Lauren O; Amer, Amal O

    2013-01-01

    Legionella pneumophila, the causative agent of Legionnaire's disease, replicates in human alveolar macrophages to establish infection. There is no human-to-human transmission and the main source of infection is L. pneumophila biofilms established in air conditioners, water fountains, and hospital equipments. The biofilm structure provides protection to the organism from disinfectants and antibacterial agents. L. pneumophila infection in humans is characterized by a subtle initial immune response, giving time for the organism to establish infection before the patient succumbs to pneumonia. Planktonic L. pneumophila elicits a strong immune response in murine, but not in human macrophages enabling control of the infection. Interactions between planktonic L. pneumophila and murine or human macrophages have been studied for years, yet the interface between biofilm-derived L. pneumophila and macrophages has not been explored. Here, we demonstrate that biofilm-derived L. pneumophila replicates significantly more in murine macrophages than planktonic bacteria. In contrast to planktonic L. pneumophila, biofilm-derived L. pneumophila lacks flagellin expression, do not activate caspase-1 or -7 and trigger less cell death. In addition, while planktonic L. pneumophila is promptly delivered to lysosomes for degradation, most biofilm-derived bacteria were enclosed in a vacuole that did not fuse with lysosomes in murine macrophages. This study advances our understanding of the innate immune response to biofilm-derived L. pneumophila and closely reproduces the natural mode of infection in human. PMID:23750338

  2. Spironolactone attenuates bleomycin-induced pulmonary injury partially via modulating mononuclear phagocyte phenotype switching in circulating and alveolar compartments.

    Directory of Open Access Journals (Sweden)

    Wen-Jie Ji

    Full Text Available BACKGROUND: Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20 mg/kg/day by oral gavage revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson' trichrome staining in bleomycin treated (2.5 mg/kg, via oropharyngeal instillation male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+ of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c- remained unaffected by spironolactone during investigation. CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.

  3. Cyclophilin A (CypA) is associated with the inflammatory infiltration and alveolar bone destruction in an experimental periodontitis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lihua [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luo Yu Road, Hongshan District, Wuhan 430079 (China); Li, Chengzhang, E-mail: l56cz@hotmail.com [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luo Yu Road, Hongshan District, Wuhan 430079 (China); Department of Periodontology, School and Hospital of Stomatology, Wuhan University, 237 Luo Yu Road, Hongshan District, Wuhan 430079 (China); Cai, Cia [Department of Periodontology, School and Hospital of Stomatology, Zhejiang University, 395 Yan An Road, Hangzhou 310006 (China); Xiang, Junbo [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luo Yu Road, Hongshan District, Wuhan 430079 (China); Cao, Zhengguo, E-mail: jery7677@hotmail.com [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, 237 Luo Yu Road, Hongshan District, Wuhan 430079 (China); Department of Periodontology, School and Hospital of Stomatology, Wuhan University, 237 Luo Yu Road, Hongshan District, Wuhan 430079 (China)

    2010-01-01

    Background and objective: CypA is able to regulate inflammatory responses and MMPs production via interaction with its cell surface receptor, EMMPRIN. This study aimed to address the possible association of CypA with pathological inflammation and destruction of periodontal tissues, and whether CypA-EMMPRIN interaction exists in periodontitis. Materials and methods: Experimental periodontitis was induced by ligation according to our previous method. Histological and radiographic examinations were performed. Western blot was used to detect CypA and EMMPRIN expressions in gingival tissues. Immunohistochemistry was applied for CypA, EMMPRIN, MMP-1, MMP-2, MMP-9, as well as cell markers of macrophage, lymphocyte and neutrophil. CypA expression, alveolar bone loss, and inflammatory infiltrations were quantified followed by correlation analyses. Results: Western blot revealed that CypA and EMMRPIN expressions were dramatically elevated in inflamed gingival tissues (ligature group) as compared to healthy gingival tissues (control group). The enhanced CypA and EMMPRIN expressions were highly consistent in cell localization on seriate sections. They were permanently co-localized in infiltrating macrophages and lymphocytes, as well as osteoclasts and osteoblasts in interradicular bone, but rarely expressed by infiltrating neutrophils. MMP-1, MMP-2, and MMP-9 expressions were also sharply increased in inflamed gingiva. MMP-2 and MMP-9 were mainly over-expressed by macrophages, while MMP-1 was over-produced by fibroblasts and infiltrating cells. The number of CypA-positive cells was strongly correlated with the ACJ-AC distance (r = 0.839, p = 0.000), the number of macrophages (r = 0.972, p = 0.000), and the number of lymphocytes (r = 0.951, p = 0.000). Conclusion: CypA is associated with the inflammatory infiltration and alveolar bone destruction of periodontitis. CypA-EMMPRIN interaction may exist in these pathological processes.

  4. Cyclophilin A (CypA) is associated with the inflammatory infiltration and alveolar bone destruction in an experimental periodontitis

    International Nuclear Information System (INIS)

    Background and objective: CypA is able to regulate inflammatory responses and MMPs production via interaction with its cell surface receptor, EMMPRIN. This study aimed to address the possible association of CypA with pathological inflammation and destruction of periodontal tissues, and whether CypA-EMMPRIN interaction exists in periodontitis. Materials and methods: Experimental periodontitis was induced by ligation according to our previous method. Histological and radiographic examinations were performed. Western blot was used to detect CypA and EMMPRIN expressions in gingival tissues. Immunohistochemistry was applied for CypA, EMMPRIN, MMP-1, MMP-2, MMP-9, as well as cell markers of macrophage, lymphocyte and neutrophil. CypA expression, alveolar bone loss, and inflammatory infiltrations were quantified followed by correlation analyses. Results: Western blot revealed that CypA and EMMRPIN expressions were dramatically elevated in inflamed gingival tissues (ligature group) as compared to healthy gingival tissues (control group). The enhanced CypA and EMMPRIN expressions were highly consistent in cell localization on seriate sections. They were permanently co-localized in infiltrating macrophages and lymphocytes, as well as osteoclasts and osteoblasts in interradicular bone, but rarely expressed by infiltrating neutrophils. MMP-1, MMP-2, and MMP-9 expressions were also sharply increased in inflamed gingiva. MMP-2 and MMP-9 were mainly over-expressed by macrophages, while MMP-1 was over-produced by fibroblasts and infiltrating cells. The number of CypA-positive cells was strongly correlated with the ACJ-AC distance (r = 0.839, p = 0.000), the number of macrophages (r = 0.972, p = 0.000), and the number of lymphocytes (r = 0.951, p = 0.000). Conclusion: CypA is associated with the inflammatory infiltration and alveolar bone destruction of periodontitis. CypA-EMMPRIN interaction may exist in these pathological processes.

  5. Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II

    DEFF Research Database (Denmark)

    Dahl, Morten; Bauer, Alison K; Arredouani, Mohamed;

    2007-01-01

    Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression ...... in lungs of ozone-resistant mice suggested an additional role protecting against inhaled oxidants. After ozone exposure, MARCO-/- mice showed greater lung injury than did MARCO+/+ mice. Ozone is known to generate oxidized, proinflammatory lipids in lung lining fluid, such as 5beta,6beta...

  6. Pulmonary alveolar proteinosis due to mycophenolate and cyclosporine combination therapy in a renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Ashfaq Hasan

    2014-01-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is an orphan disease characterized by the accumulation of excess of surfactant within alveoli and bronchioles. The primary form of PAP (P-PAP; also referred to as idiopathic or autoimmune is the most common form. It is mediated through a circulating neutralizing antibody against granulocyte-macrophage colony-stimulating factor. Secondary PAP (S-PAP can be induced by a host of inciting agents and is far more liable to progress to terminal respiratory failure. We describe a rare case of S-PAP occurring in a renal transplant recipient due to mycophenolate and cyclosporine combination-therapy, which resolved spontaneously following withdrawal of these drugs.

  7. Claudins and alveolar epithelial barrier function in the lung

    OpenAIRE

    Frank, James A.

    2012-01-01

    The alveolar epithelium of the lung constitutes a unique interface with the outside environment. This thin barrier must maintain a surface for gas transfer while being continuously exposed to potentially hazardous environmental stimuli. Small differences in alveolar epithelial barrier properties could therefore have a large impact on disease susceptibility or outcome. Moreover, recent work has focused attention on the alveolar epithelium as central to several lung diseases, including acute lu...

  8. Pulmonary Surfactant Surface Tension Influences Alveolar Capillary Shape and Oxygenation

    OpenAIRE

    Ikegami, Machiko; Weaver, Timothy E.; Grant, Shawn N.; Whitsett, Jeffrey A.

    2009-01-01

    Alveolar capillaries are located in close proximity to the alveolar epithelium and beneath the surfactant film. We hypothesized that the shape of alveolar capillaries and accompanying oxygenation are influenced by surfactant surface tension in the alveolus. To prove our hypothesis, surfactant surface tension was regulated by conditional expression of surfactant protein (SP)-B in Sftpb−/− mice, thereby inhibiting surface tension–lowering properties of surfactant in vivo within 24 hours after d...

  9. Alveolar epithelial type II cell: defender of the alveolus revisited

    OpenAIRE

    Fehrenbach Heinz

    2001-01-01

    Abstract In 1977, Mason and Williams developed the concept of the alveolar epithelial type II (AE2) cell as a defender of the alveolus. It is well known that AE2 cells synthesise, secrete, and recycle all components of the surfactant that regulates alveolar surface tension in mammalian lungs. AE2 cells influence extracellular surfactant transformation by regulating, for example, pH and [Ca2+] of the hypophase. AE2 cells play various roles in alveolar fluid balance, coagulation/fibrinolysis, a...

  10. Alveolar pressure during high-frequency jet ventilation

    OpenAIRE

    Vught, Adrianus; Versprille, Adrian; Jansen, Jos

    1990-01-01

    textabstractWe studied the influence of ventilatory frequency (1-5 Hz), tidal volume, lung volume and body position on the end-expiratory alveolar-to-tracheal pressure difference during high-frequency jet ventilation (HFJV) in Yorkshire piglets. The animals were anesthetized and paralysed. Alveolar pressure was estimated with the clamp off method, which was performed by a computer controlled ventilator and which had been extensively tested on its feasibility. The alveolar-to-tracheal pressure...

  11. Pulmonary Alveolar Proteinosis in Children: A case series

    OpenAIRE

    seyyed Ahmad Tabatabaei; abdollah karimi; Sedigheh Rafiee Tabatabaei; B Radpay; Farzaneh Jadali

    2010-01-01

    Pulmonary Alveolar Proteinosis(PAP) is a rare disease of unknown etiology, characterized by the accumulation of proteinoceous material in the alveoli that is rich in lipid and is positive on periodic acid-Schiff(PAS) stain. PAP is rare in children. Two forms are encountered in pediatric practice: congenital alveolar proteinosis (CAP) and a later–onset form that is generally less severe. Broncho-alveolar lavage is the key to diagnosis. Therapeutic lung lavages are the only effective treatment ...

  12. Isolation and Culture of Human Alveolar Type II Pneumocytes.

    Science.gov (United States)

    Witherden, I R; Tetley, T D

    2001-01-01

    Alveolar type II pneumocytes (alveolar type II cells; TII cells) play an important role in the homeostasis of the alveolar unit. They are the progenitor cells to the type I pneumocyte and are therefore responsible for regeneration of alveolar epithelium following alveolar epithelial cell damage. The type I cell covers over 90% of the alveolar surface, reflecting its capacity to stretch into a flattened cell with very little depth (approx. 0.1 µm), but with a large surface area, to facilitate gas exchange. Nevertheless, the type II cell outnumbers type I cells, estimated to be by 2:1 in rodents. Most of the type II cell lies buried in the interstitium of the alveolus, with only the apical tip of the cell reaching into the airspace, through which another crucial function, provision of alveolar surfactant, occurs. Surfactant synthesis and secretion is a unique feature of type II cells; surfactant consists of a high proportion of phospholipids (approx. 90%) and a small proportion of protein (approx. 10%), which contains surfactant apoprotein (SP), of which four have so far been described, SP-A, SP-B, SP-C, and SP-D (1,2). Surfactant is highly surface active and is essential to prevent alveolar collapse. In addition, surfactant has many other roles, including pulmonary host defense. Compromised surfactant synthesis and function are believed to be a feature of numerous disease states (1,2), including infant respiratory distress syndrome, adult respiratory distress syndrome, alveolar proteinosis, and microbial infection. PMID:21336897

  13. Alveolar type II cells express a high-affinity receptor for pulmonary surfactant protein A

    International Nuclear Information System (INIS)

    Primary cultures of rat alveolar type II cells bind radiolabeled pulmonary surfactant protein A (SP-A) with high affinity. The binding of 125I-labeled SP-A is time- and temperature-dependent and is not accompanied by significant degradation. The binding process is saturable at low concentrations of SP-A, and unlabeled SP-A readily competes with labeled SP-A for cellular binding sites. Subsequent to binding, two pools of cell-associated 125I-labeled SP-A can be identified based upon sensitivity to trypsin at 0 degree C. It is likely that the trypsin-sensitive pool comprises 125I-labeled SP-A bound to the cell surface and the trypsin-insensitive pool comprises the internalized protein. Scatchard analysis of cell surface binding of SP-A at 0.1-10 μg/ml shows positive cooperativity at concentrations between 0.1 and 1 μg/ml. Hill plots give nH = 1.34 ± 0.08 with an apparent dissociation constant K'd = 1.02 ± 0.32 μg/ml. The binding of SP-A to type II cells shows an absolute requirement for Ca2+. The putative receptor for SP-A is unaffected by treatment of type II cells with a variety of proteases and N-Glycanase. Alveolar macrophages also exhibit high-affinity binding of SP-A, but rat lung fibroblasts and the alveolar epithelial cell line L2 exhibit only nonspecific binding

  14. Activation of macrophage nuclear factor-κB and induction of inducible nitric oxide synthase by LPS

    OpenAIRE

    Yan Zhong-Qun; Li Ying-Hua; Brauner Annelie; Tullus Kjell

    2002-01-01

    Abstract Background Chronic lung disease (CLD) of prematurity is a major problem of neonatal care. Bacterial infection and inflammatory response have been thought to play an important role in the development of CLD and steroids have been given, with some benefit, to neonates with this disease. In the present study, we assessed the ability of lipopolysaccharide (LPS) to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS) and activate ...

  15. Testing Nucleoside Analogues as Inhibitors of Bacillus anthracis Spore Germination In Vitro and in Macrophage Cell Culture ▿

    OpenAIRE

    Alvarez, Zadkiel; Lee, Kyungae; Abel-Santos, Ernesto

    2010-01-01

    Bacillus anthracis, the etiological agent of anthrax, has a dormant stage in its life cycle known as the endospore. When conditions become favorable, spores germinate and transform into vegetative bacteria. In inhalational anthrax, the most fatal manifestation of the disease, spores enter the organism through the respiratory tract and germinate in phagosomes of alveolar macrophages. Germinated cells can then produce toxins and establish infection. Thus, germination is a crucial step for the i...

  16. Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces.

    Science.gov (United States)

    Kaneko, Keita; Togami, Kohei; Yamamoto, Eri; Wang, Shujun; Morimoto, Kazuhiro; Itagaki, Shirou; Chono, Sumio

    2016-10-01

    The distribution characteristics of aerosolized PEGylated liposomes in alveolar epithelial lining fluid (ELF) were examined in rats, and the ensuing mechanisms were investigated in the in vitro uptake and protein adsorption experiments. Nonmodified or PEGylated liposomes (particle size 100 nm) were aerosolized into rat lungs. PEGylated liposomes were distributed more sustainably in ELFs than nonmodified liposomes. Furthermore, the uptake of PEGylated liposomes by alveolar macrophages (AMs) was less than that of nonmodified liposomes. In further in vitro uptake experiments, nonmodified and PEGylated liposomes were opsonized with rat ELF components and then added to NR8383 cells as cultured rat AMs. The uptake of opsonized PEGylated liposomes by NR8383 cells was lower than that of opsonized nonmodified liposomes. Moreover, the protein absorption levels in opsonized PEGylated liposomes were lower than those in opsonized nonmodified liposomes. These findings suggest that sustained distributions of aerosolized PEGylated liposomes in ELFs reflect evasion of liposomal opsonization with surfactant proteins and consequent reductions in uptake by AMs. These data indicate the potential of PEGylated liposomes as aerosol-based drug delivery system that target ELF for the treatment of respiratory diseases.

  17. Radiation-induced strain differences in mouse alveolar inflammatory cell apoptosis.

    Science.gov (United States)

    O'Brien, Thomas J; Létuvé, Séverine; Haston, Christina K

    2005-01-01

    Whole-thorax irradiation results in the development of the diffuse inflammatory response alveolitis in C3H/HeJ (C3H) mice and a milder alveolitis with fibrosis in C57BL/6J (B6) mice. In this study, we investigate if this mouse strain difference in response to radiation is due to differences in lung inflammatory cell apoptosis. Mice of the C3H and B6 strains were given a radiation dose of 18 Gy to the thorax and the animals were sacrificed at 11 or 18 weeks following exposure or when they were moribund. Active caspase-3 staining was used to identify apoptotic cells in the alveolar space of histological lung sections from the mice. The apoptotic index of B6 mice was greater than that of C3H mice at 11 weeks postirradiation (17.8% of airspace cells vs. 7.8%, p = 0.028) and in mice sacrificed because of illness (27.3% vs. 14.4%, p = 0.036). No C3H mice survived to the later time point. The inflammatory cells undergoing apoptosis in the mouse lungs were morphologically consistent with alveolar macrophages. We conclude that a difference in inflammatory cell apoptosis may contribute to the disparate pulmonary radiation response of these mouse strains.

  18. Epidemiological and clinical features of idiopathic pulmonary alveolar proteinosis in Japan.

    Science.gov (United States)

    Inoue, Yoshikazu; Nakata, Koh; Arai, Toru; Tazawa, Ryushi; Hamano, Emi; Nukiwa, Toshihiro; Kudo, Koichiro; Keicho, Naoto; Hizawa, Nobuyuki; Yamaguchi, Etsuro; Eda, Ryosuke; Oishi, Kazunori; Maeda, Yuuka; Koreeda, Yukiko; Kodo, Naohiko; Sakatani, Mitsunori

    2006-01-01

    Idiopathic pulmonary alveolar proteinosis (IPAP) is a rare disease characterized by excessive amounts of lipoproteinaceous material in the alveolus. This report presents an interim analysis of nationwide epidemiological data from Japanese patients with pulmonary alveolar proteinosis, and the roles of serum markers for IPAP. (i) The nationwide demographic data from 166 Japanese patients with IPAP are shown. The female to male ratio was 1:2, and the average age was 51 +/- 14 years old (age range: 15-79 years) at registration or diagnosis. A total of 30% of patients with IPAP have a poor clinical course. In total, 30% of patients were treated with whole lung lavage therapy (WLL). Under WLL, the patients significantly improved in the short term, but 40% of the patients who underwent WLL worsened again. A new strategy such as granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for intractable PAP is required. (ii) The correlation of serum KL-6, carcinoembryonic antigen, surfactant proteins D and A, and LDH with disease severity suggests their potential as disease markers. In contrast, serum anti-GM-CSF antibody did not correlate with disease severity, but is a specific marker for the diagnosis of IPAP. The combined measurements of the serum markers may well prove very useful for both the diagnosis and the management of IPAP patients. PMID:16423273

  19. Neutralization and clearance of GM-CSF by autoantibodies in pulmonary alveolar proteinosis.

    Science.gov (United States)

    Piccoli, Luca; Campo, Ilaria; Fregni, Chiara Silacci; Rodriguez, Blanca Maria Fernandez; Minola, Andrea; Sallusto, Federica; Luisetti, Maurizio; Corti, Davide; Lanzavecchia, Antonio

    2015-01-01

    Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF activity using an in vitro bioassay, depending on the experimental conditions, while, when injected in mice together with human GM-CSF, they lead to the accumulation of a large pool of circulating GM-CSF that remains partially bioavailable. In contrast, a combination of three non-cross-competing antibodies completely neutralizes GM-CSF activity in vitro by sequestering the cytokine in high-molecular-weight complexes, and in vivo promotes the rapid degradation of GM-CSF-containing immune complexes in an Fc-dependent manner. Taken together, these findings provide a plausible explanation for the severe phenotype of PAP patients and for the safety of treatments based on single anti-GM-CSF monoclonal antibodies. PMID:26077231

  20. Establishment and evaluation of a stable cattle type II alveolar epithelial cell line.

    Directory of Open Access Journals (Sweden)

    Feng Su

    Full Text Available Macrophages and dendritic cells are recognized as key players in the defense against mycobacterial infection. Recent research has confirmed that alveolar epithelial cells (AECs also play important roles against mycobacterium infections. Thus, establishing a stable cattle AEC line for future endogenous immune research on bacterial invasion is necessary. In the present study, we first purified and immortalized type II AECs (AEC II cells by transfecting them with a plasmid containing the human telomerase reverse trancriptase gene. We then tested whether or not the immortalized cells retained the basic physiological properties of primary AECs by reverse-transcription polymerase chain reaction and Western blot. Finally, we tested the secretion capacity of immortalized AEC II cells upon stimulation by bacterial invasion. The cattle type II alveolar epithelial cell line (HTERT-AEC II that we established retained lung epithelial cell characteristics: the cells were positive for surfactants A and B, and they secreted tumor necrosis factor-α and interleukin-6 in response to bacterial invasion. Thus, the cell line we established is a potential tool for research on the relationship between AECs and Mycobacterium tuberculosis.

  1. Role of cytoskeleton in cytokine production from lung alveolar epithelial cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Cytokines are involved in both host defense and inflammatory lung injury. Recent work from our laboratory and others has demonstrated that in addition to classical immune cells, lung alveolar epithelial cells (or pneumocytes) can also produce cytokines in response to various stimuli. This new knowledge has advanced our view of the host defense system in the lung. The regulatory mechanisms of cytokine production have been studied in great detail at various cellular and molecular levels, but the mechanisms of intracellular cytokine transport are largely unknown. Our recent studies suggest that the cytoskeleton could play an important role in mediating intracellular cytokine trafficking. This could be an important regulatory step for cytokine production. For example, lipopolyssacharide (LPS) induced tumor necrosis factor-α (TNF-α) from rat pneumocytes, which was further enhanced by a microfilament-disrupting agent. LPS also induced macrophage inflammatory protein-2(MIP-2), a chemokine for neutrophil recruitment and activation, from rat pneumocytes. This effect was enhanced by microtubule-disrupting agents. We speculate that both microfilaments and microtubules are involved in regulating cytokine transportation in pneumocytes through different mechanisms. Further investigation in on going in my laboratory. From a clinical perspective, if we understand the mechanisms regulating cytokine production and release from lung alveolar epithelial cells, we may be able to enhance or inhibit release of crucial cytokines depending on the clinical situation.

  2. Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces.

    Science.gov (United States)

    Kaneko, Keita; Togami, Kohei; Yamamoto, Eri; Wang, Shujun; Morimoto, Kazuhiro; Itagaki, Shirou; Chono, Sumio

    2016-10-01

    The distribution characteristics of aerosolized PEGylated liposomes in alveolar epithelial lining fluid (ELF) were examined in rats, and the ensuing mechanisms were investigated in the in vitro uptake and protein adsorption experiments. Nonmodified or PEGylated liposomes (particle size 100 nm) were aerosolized into rat lungs. PEGylated liposomes were distributed more sustainably in ELFs than nonmodified liposomes. Furthermore, the uptake of PEGylated liposomes by alveolar macrophages (AMs) was less than that of nonmodified liposomes. In further in vitro uptake experiments, nonmodified and PEGylated liposomes were opsonized with rat ELF components and then added to NR8383 cells as cultured rat AMs. The uptake of opsonized PEGylated liposomes by NR8383 cells was lower than that of opsonized nonmodified liposomes. Moreover, the protein absorption levels in opsonized PEGylated liposomes were lower than those in opsonized nonmodified liposomes. These findings suggest that sustained distributions of aerosolized PEGylated liposomes in ELFs reflect evasion of liposomal opsonization with surfactant proteins and consequent reductions in uptake by AMs. These data indicate the potential of PEGylated liposomes as aerosol-based drug delivery system that target ELF for the treatment of respiratory diseases. PMID:27334278

  3. Characteristic aspects of alveolar proteinosis diagnosis Aspectos característicos do diagnóstico da proteinose alveolar

    OpenAIRE

    Thiago Prudente Bártholo; José Gustavo Pugliese; Luiz Carlos Aguiar Vaz; Cláudia Henrique da Costa; Rogério Rufino

    2012-01-01

    Alveolar proteinosis is an uncommon pulmonary disease characterized by an accumulation of surfactant in terminal airway and alveoli, thereby impairing gas exchange and engendering respiratory insufficiency in some cases. Three clinically and etiologically distinct forms of pulmonary alveolar proteinosis are recognized: congenital, secondary and idiopathic, the latter corresponding to 90% of the cases. In this case report we present a young male patient that was diagnosed with alveolar protein...

  4. Segment distraction to reduce a wide alveolar cleft before alveolar bone grafting.

    NARCIS (Netherlands)

    Binger, T.; Katsaros, C.; Rucker, M.; Spitzer, W.J.

    2003-01-01

    OBJECTIVE: To demonstrate a method for reduction of wide alveolar clefts prior to bone grafting. This method aims to facilitate bone grafting and achieve adequate soft tissue coverage of the graft with attached gingiva. CASE REPORT: Treatment of a patient with bilateral cleft lip and palate with a s

  5. Incorporation of tritiated thymidine by epithelial and interstitial cells in bronchiolar-alveolar regions of asbestos-exposed rats

    International Nuclear Information System (INIS)

    Inhaled asbestos causes progressive interstitial lung disease. The authors have performed a series of studies to elucidate early pathogenetic events at sites of fiber deposition in asbestos-exposed rats. This study reports that a single 5-hour exposure to chrysotile asbestos induces significant increases in incorporation of tritiated thymidine (3HTdR) into nuclei of epithelial and interstitial cells of bronchiolar-alveolar regions. No cell populations in air-exposed or carbonyl iron-exposed control animals exhibited more than 1% labeling at any point in time. Immediately after the 5-hour asbestos exposure, incorporation was normal. By 19 hours after exposure there was a significant increase in incorporation of 3HTdR, particularly by Type II epithelial cells of the first alveolar duct bifurcations. The greatest increase in degree of incorporation (up to 18-fold) was observed 24 hours after exposure, and increased percentages of 3HTdR-labeled cells were maintained through the 48 hours postexposure period. Normal labeling was present by 8 days after exposure, and this level remained through the 1-month period studied. This apparent mitogenic response correlates with increased numbers of bronchiolar-alveolar epithelial and interstitial cells demonstrated by ultrastructural morphometry in correlative studies. The authors speculate that the incorporation of 3HTdR could be induced by the direct effects of inhaled fibers or by mitogenic factors released from macrophages attracted to the inhaled asbestos

  6. Classical and alternative macrophage activation in the lung following ozone-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Sunil, Vasanthi R., E-mail: sunilva@pharmacy.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States); Patel-Vayas, Kinal; Shen, Jianliang [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy, Piscataway, NJ 08854 (United States)

    2012-09-01

    Ozone is a pulmonary irritant known to cause oxidative stress, inflammation and tissue injury. Evidence suggests that macrophages play a role in the pathogenic response; however, their contribution depends on the mediators they encounter in the lung which dictate their function. In these studies we analyzed the effects of ozone-induced oxidative stress on the phenotype of alveolar macrophages (AM). Exposure of rats to ozone (2 ppm, 3 h) resulted in increased expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG), as well as heme oxygenase-1 (HO-1) in AM. Whereas 8-OHdG was maximum at 24 h, expression of HO-1 was biphasic increasing after 3 h and 48–72 h. Cleaved caspase-9 and beclin-1, markers of apoptosis and autophagy, were also induced in AM 24 h post-ozone. This was associated with increased bronchoalveolar lavage protein and cells, as well as matrix metalloproteinase (MMP)-2 and MMP-9, demonstrating alveolar epithelial injury. Ozone intoxication resulted in biphasic activation of the transcription factor, NFκB. This correlated with expression of monocyte chemotactic protein‐1, inducible nitric oxide synthase and cyclooxygenase‐2, markers of proinflammatory macrophages. Increases in arginase-1, Ym1 and galectin-3 positive anti-inflammatory/wound repair macrophages were also observed in the lung after ozone inhalation, beginning at 24 h (arginase-1, Ym1), and persisting for 72 h (galectin-3). This was associated with increased expression of pro-surfactant protein-C, a marker of Type II cell proliferation and activation, important steps in wound repair. These data suggest that both proinflammatory/cytotoxic and anti-inflammatory/wound repair macrophages are activated early in the response to ozone-induced oxidative stress and tissue injury. -- Highlights: ► Lung macrophages are highly sensitive to ozone induced oxidative stress. ► Ozone induces autophagy and apoptosis in lung macrophages. ► Proinflammatory and wound repair macrophages are activated

  7. Classical and alternative macrophage activation in the lung following ozone-induced oxidative stress

    International Nuclear Information System (INIS)

    Ozone is a pulmonary irritant known to cause oxidative stress, inflammation and tissue injury. Evidence suggests that macrophages play a role in the pathogenic response; however, their contribution depends on the mediators they encounter in the lung which dictate their function. In these studies we analyzed the effects of ozone-induced oxidative stress on the phenotype of alveolar macrophages (AM). Exposure of rats to ozone (2 ppm, 3 h) resulted in increased expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG), as well as heme oxygenase-1 (HO-1) in AM. Whereas 8-OHdG was maximum at 24 h, expression of HO-1 was biphasic increasing after 3 h and 48–72 h. Cleaved caspase-9 and beclin-1, markers of apoptosis and autophagy, were also induced in AM 24 h post-ozone. This was associated with increased bronchoalveolar lavage protein and cells, as well as matrix metalloproteinase (MMP)-2 and MMP-9, demonstrating alveolar epithelial injury. Ozone intoxication resulted in biphasic activation of the transcription factor, NFκB. This correlated with expression of monocyte chemotactic protein‐1, inducible nitric oxide synthase and cyclooxygenase‐2, markers of proinflammatory macrophages. Increases in arginase-1, Ym1 and galectin-3 positive anti-inflammatory/wound repair macrophages were also observed in the lung after ozone inhalation, beginning at 24 h (arginase-1, Ym1), and persisting for 72 h (galectin-3). This was associated with increased expression of pro-surfactant protein-C, a marker of Type II cell proliferation and activation, important steps in wound repair. These data suggest that both proinflammatory/cytotoxic and anti-inflammatory/wound repair macrophages are activated early in the response to ozone-induced oxidative stress and tissue injury. -- Highlights: ► Lung macrophages are highly sensitive to ozone induced oxidative stress. ► Ozone induces autophagy and apoptosis in lung macrophages. ► Proinflammatory and wound repair macrophages are activated

  8. Nostril Base Augmentation Effect of Alveolar Bone Graft

    Directory of Open Access Journals (Sweden)

    Woojin Lee

    2013-09-01

    Full Text Available Background The aims of alveolar bone grafting are closure of the fistula, stabilization ofthe maxillary arch, support for the roots of the teeth adjacent to the cleft on each side.We observed nostril base augmentation in patients with alveolar clefts after alveolar bonegrafting. The purpose of this study was to evaluate the nostril base augmentation effect ofsecondary alveolar bone grafting in patients with unilateral alveolar cleft.Methods Records of 15 children with alveolar clefts who underwent secondary alveolar bonegrafting with autogenous iliac cancellous bone between March of 2011 and May of 2012 werereviewed. Preoperative and postoperative worm’s-eye view photographs and reconstructedthree-dimensional computed tomography (CT scans were used for photogrammetry. Thedepression of the nostril base and thickness of the philtrum on the cleft side were measuredin comparison to the normal side. The depression of the cleft side pyriform aperture wasmeasured in comparison to the normal side on reconstructed three-dimensional CT.Results Significant changes were seen in the nostril base (P=0.005, the philtrum length(P=0.013, and the angle (P=0.006. The CT measurements showed significant changes in thepyriform aperture (P<0.001 and the angle (P<0.001.Conclusions An alveolar bone graft not only fills the gap in the alveolar process but alsoaugments the nostril base after surgery. In this study, only an alveolar bone graft was performedto prevent bias from other procedures. Nostril base augmentation can be achieved byperforming alveolar bone grafts in children, in whom invasive methods are not advised.

  9. An estimation of mechanical stress on alveolar walls during repetitive alveolar reopening and closure.

    Science.gov (United States)

    Chen, Zheng-Long; Song, Yuan-Lin; Hu, Zhao-Yan; Zhang, Su; Chen, Ya-Zhu

    2015-08-01

    Alveolar overdistension and mechanical stresses generated by repetitive opening and closing of small airways and alveoli have been widely recognized as two primary mechanistic factors that may contribute to the development of ventilator-induced lung injury. A long-duration exposure of alveolar epithelial cells to even small, shear stresses could lead to the changes in cytoskeleton and the production of inflammatory mediators. In this paper, we have made an attempt to estimate in situ the magnitudes of mechanical stresses exerted on the alveolar walls during repetitive alveolar reopening by using a tape-peeling model of McEwan and Taylor (35). To this end, we first speculate the possible ranges of capillary number (Ca) ≡ μU/γ (a dimensionless combination of surface tension γ, fluid viscosity μ, and alveolar opening velocity U) during in vivo alveolar opening. Subsequent calculations show that increasing respiratory rate or inflation rate serves to increase the values of mechanical stresses. For a normal lung, the predicted maximum shear stresses are surface tension or viscosity, the maximum shear stress will notably increase, even at a slow respiratory rate. Similarly, the increased pressure gradients in the case of elevated surface or viscosity may lead to a pressure drop >300 dyn/cm(2) across a cell, possibly inducing epithelial hydraulic cracks. In addition, we have conceived of a geometrical model of alveolar opening to make a prediction of the positive end-expiratory pressure (PEEP) required to splint open a collapsed alveolus, which as shown by our results, covers a wide range of pressures, from several centimeters to dozens of centimeters of water, strongly depending on the underlying pulmonary conditions. The establishment of adequate regional ventilation-to-perfusion ratios may prevent recruited alveoli from reabsorption atelectasis and accordingly, reduce the required levels of PEEP. The present study and several recent animal experiments likewise

  10. Dry powder cationic lipopolymeric nanomicelle inhalation for targeted delivery of antitubercular drug to alveolar macrophage

    Directory of Open Access Journals (Sweden)

    Vadakkan MV

    2013-08-01

    Full Text Available Mithun Varghese Vadakkan,1 K Annapoorna,2 KC Sivakumar,3 Sathish Mundayoor,2 GS Vinod Kumar1 1Chemical Biology, 2Mycobacterium Research Group, 3Bioinformatics Facility, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India Abstract: Excipients having self-assembling properties are less explored in the field of dry powder inhalation (DPI technology. An amphiphilic lipopolymer system was developed using stearic acid (SA and branched polyethyleneimine (BPEI (1800 Dalton, at different proportions by covalent conjugation. A molecular dynamic (MD simulation tool was employed for predicting the carrier behavior in a polar in vivo condition. The structural characterization was carried out using nuclear magnetic resonance spectroscopy (NMR and Fourier transform infrared (FTIR spectroscopy. The physical nature of the lipopolymer was analyzed by differential scanning calorimetry. Determination of zeta potential and diameter of the micelles showed existence of cationic particles in the nano size range when a lower number of primary amino groups of BPEI was grafted with SA. The rifampicin (RIF-loaded lipopolymer was also formulated further into spray-dried microparticles. Powder X-ray diffraction (PXRD studies revealed that the RIF API (active pharmaceutical ingredient exists as molecular dispersion in spray-dried microparticles. Topological analysis of the spray-dried nanomicelle was carried out using scanning electron microscopy (SEM. A large population of the drug-carrying particles were found to be under the inhalable size range (fine particle fraction 67.88% ± 3%. In vitro drug release kinetics from spray-dried nanomicelles were carried out at lung fluid pH. Keywords: molecular dynamics, dry powder inhalation, pulmonary tuberculosis, nanomicelle, lipopolymer, rifampicin

  11. Binding of radiolabeled asbestos fibers to guinea pig (gp) alveolar macrophages (AM)

    International Nuclear Information System (INIS)

    The mechanism by which fibrogenic particulates cause pulmonary fibrosis in humans is not understood, but is likely to involve the AM. Using two fibrogenic particulates, namely, chrysotile (CHR) and crocidolite (CRO) asbestos and gpAM as components of an in vitro model system, the authors have shown that CHR stimulates the gpAM to release superoxide anion, but CRO does not. To examine whether this difference in stimulatory abilities is a result of differences in cell-asbestos binding they have developed an efficient procedure that radiolabels asbestos fibers while retaining their bioactivity. The fibers are labeled with 68Ge. The 68Ge decays into 68Ga, which then can be detected by its characteristic position emission. Both CHR and CRO asbestos were radiolabled successfully. Mild reaction conditions and short reaction times were found under which >90% of the added 68Ge and 68Ga bound to the fibers. The radiolabel was retained even after washing the fibers extensively with physiologic buffers. A density gradient procedure was developed to quantitate the binding of asbestos to gpAM in suspension. The binding of both fibers increased with time over one hr. Thus, these results indicate that although both CHR and CRO interact with the gpAM, only CHR interacts productively to stimulate superoxide anion release

  12. Amelioration of emphysema in mice through lentiviral transduction of long-lived pulmonary alveolar macrophages

    OpenAIRE

    Wilson, Andrew A.; Murphy, George J.; Hamakawa, Hiroshi; Kwok, Letty W.; Srinivasan, Sreedevi; Hovav, Avi-Hai; Mulligan, Richard C.; Amar, Salomon; Suki, Bela; Kotton, Darrell N.

    2009-01-01

    Directed gene transfer into specific cell lineages in vivo is an attractive approach for both modulating gene expression and correcting inherited mutations such as emphysema caused by human α1 antitrypsin (hAAT) deficiency. However, somatic tissues are mainly comprised of heterogeneous, differentiated cell lineages that can be short lived and difficult to specifically transfect. Here, we describe an intratracheally instilled lentiviral system able to deliver genes selectively to as many as 70...

  13. Rhinovirus exposure impairs immune responses to bacterial products in human alveolar macrophages

    NARCIS (Netherlands)

    Oliver, B G G; Lim, S; Wark, P; Laza-Stanca, V; King, N; Black, J L; Burgess, J K; Roth, M; Johnston, S L

    2008-01-01

    BACKGROUND: Rhinovirus infection is responsible for considerable morbidity and mortality as the major cause of exacerbations of asthma, and is also known to induce exacerbations of cystic fibrosis and chronic obstructive pulmonary disease. Exacerbations of these diseases are also frequently associat

  14. Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

    Directory of Open Access Journals (Sweden)

    Boczkowski Jorge

    2009-04-01

    Full Text Available Abstract Background A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red and analyzed 2 time points (3 and 24 hours for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality was calculated. Results The use of MTT assay on THP-1 cells exposed for 24 hours appears to be the most sensitive experimental design to assess the cytotoxic effect of one nanoparticle. With this experimental set-up, Copper- and Zinc-based nanoparticles appear to be the most toxic. Titania, Alumina, Ceria and Zirconia-based nanoparticles show moderate toxicity, and no toxicity was observed for Tungsten Carbide. No correlation between cytotoxicity and equivalent spherical diameter or specific surface area was found. Conclusion Our study clearly highlights the difference of sensitivity between cell types and cytotoxicity assays that has to be carefully taken into account when assessing nanoparticles toxicity.

  15. Biology of Bony Fish Macrophages

    OpenAIRE

    Hodgkinson, Jordan W.; Leon Grayfer; Miodrag Belosevic

    2015-01-01

    Macrophages are found across all vertebrate species, reside in virtually all animal tissues, and play critical roles in host protection and homeostasis. Various mechanisms determine and regulate the highly plastic functional phenotypes of macrophages, including antimicrobial host defenses (pro-inflammatory, M1-type), and resolution and repair functions (anti-inflammatory/regulatory, M2-type). The study of inflammatory macrophages in immune defense of teleosts has garnered much attention, and ...

  16. Overexpression of sICAM-1 in the Alveolar Epithelial Space Results in an Exaggerated Inflammatory Response and Early Death in Gram Negative Pneumonia

    Directory of Open Access Journals (Sweden)

    Curtis Jeffery L

    2011-01-01

    Full Text Available Abstract Background A sizeable body of data demonstrates that membrane ICAM-1 (mICAM-1 plays a significant role in host defense in a site-specific fashion. On the pulmonary vascular endothelium, mICAM-1 is necessary for normal leukocyte recruitment during acute inflammation. On alveolar epithelial cells (AECs, we have shown previously that the presence of normal mICAM-1 is essential for optimal alveolar macrophage (AM function. We have also shown that ICAM-1 is present in the alveolar space as a soluble protein that is likely produced through cleavage of mICAM-1. Soluble intercellular adhesion molecule-1 (sICAM-1 is abundantly present in the alveolar lining fluid of the normal lung and could be generated by proteolytic cleavage of mICAM-1, which is highly expressed on type I AECs. Although a growing body of data suggesting that intravascular sICAM-1 has functional effects, little is known about sICAM-1 in the alveolus. We hypothesized that sICAM-1 in the alveolar space modulates the innate immune response and alters the response to pulmonary infection. Methods Using the surfactant protein C (SPC promoter, we developed a transgenic mouse (SPC-sICAM-1 that constitutively overexpresses sICAM-1 in the distal lung, and compared the responses of wild-type and SPC-sICAM-1 mice following intranasal inoculation with K. pneumoniae. Results SPC-sICAM-1 mice demonstrated increased mortality and increased systemic dissemination of organisms compared with wild-type mice. We also found that inflammatory responses were significantly increased in SPC-sICAM-1 mice compared with wild-type mice but there were no difference in lung CFU between groups. Conclusions We conclude that alveolar sICAM-1 modulates pulmonary inflammation. Manipulating ICAM-1 interactions therapeutically may modulate the host response to Gram negative pulmonary infections.

  17. Bioelectric modulation of macrophage polarization

    Science.gov (United States)

    Li, Chunmei; Levin, Michael; Kaplan, David L.

    2016-02-01

    Macrophages play a critical role in regulating wound healing and tissue regeneration by changing their polarization state in response to local microenvironmental stimuli. The native roles of polarized macrophages encompass biomaterials and tissue remodeling needs, yet harnessing or directing the polarization response has been largely absent as a potential strategy to exploit in regenerative medicine to date. Recent data have revealed that specific alteration of cells’ resting potential (Vmem) is a powerful tool to direct proliferation and differentiation in a number of complex tissues, such as limb regeneration, craniofacial patterning and tumorigenesis. In this study, we explored the bioelectric modulation of macrophage polarization by targeting ATP sensitive potassium channels (KATP). Glibenclamide (KATP blocker) and pinacidil (KATP opener) treatment not only affect macrophage polarization, but also influence the phenotype of prepolarized macrophages. Furthermore, modulation of cell membrane electrical properties can fine-tune macrophage plasticity. Glibenclamide decreased the secretion and gene expression of selected M1 markers, while pinacidil augmented M1 markers. More interestingly, glibencalmide promoted macrophage alternative activation by enhancing certain M2 markers during M2 polarization. These findings suggest that control of bioelectric properties of macrophages could offer a promising approach to regulate macrophage phenotype as a useful tool in regenerative medicine.

  18. Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway.

    Science.gov (United States)

    Moon, H-G; Cao, Y; Yang, J; Lee, J H; Choi, H S; Jin, Y

    2015-01-01

    Despite decades of research, the pathogenesis of acute respiratory distress syndrome (ARDS) remains poorly understood, thus impeding the development of effective treatment. Diffuse alveolar damage (DAD) and lung epithelial cell death are prominent features of ARDS. Lung epithelial cells are the first line of defense after inhaled stimuli, such as in the case of hyperoxia. We hypothesized that lung epithelial cells release 'messenger' or signaling molecules to adjacent or distant macrophages, thereby initiating or propagating inflammatory responses after noxious insult. We found that, after hyperoxia, a large amount of extracellular vesicles (EVs) were generated and released into bronchoalveolar lavage fluid (BALF). These hyperoxia-induced EVs were mainly derived from live lung epithelial cells as the result of hyperoxia-associated endoplasmic reticulum (ER) stress. These EVs were remarkably different from epithelial 'apoptotic bodies', as reflected by the significantly smaller size and differentially expressed protein markers. These EVs fall mainly in the size range of the exosomes and smaller microvesicles (MVs) (50-120 nm). The commonly featured protein markers of apoptotic bodies were not found in these EVs. Treating alveolar macrophages with hyperoxia-induced, epithelial cell-derived EVs led to an increased secretion of pro-inflammatory cytokines and macrophage inflammatory protein 2 (MIP-2). Robustly increased macrophage and neutrophil influx was found in the lung tissue of the mice intranasally treated with hyperoxia-induced EVs. It was determined that EV-encapsulated caspase-3 was largely responsible for the alveolar macrophage activation via the ROCK1 pathway. Caspase-3-deficient EVs induced less cytokine/MIP-2 release, reduced cell counts in BALF, less neutrophil infiltration and less inflammation in lung parenchyma, both in vitro and in vivo. Furthermore, the serum circulating EVs were increased and mainly derived from lung epithelial cells after

  19. Macrophage elastase (MMP-12: a pro-inflammatory mediator?

    Directory of Open Access Journals (Sweden)

    Soazig Nénan

    2005-03-01

    Full Text Available As many metalloproteinases (MMPs, macrophage elastase (MMP-12 is able to degrade extracellular matrix components such as elastin and is involved in tissue remodeling processes. Studies using animal models of acute and chronic pulmonary inflammatory diseases, such as pulmonary fibrosis and chronic obstrutive pulmonary disease (COPD, have given evidences that MMP-12 is an important mediator of the pathogenesis of these diseases. However, as very few data regarding the direct involvement of MMP-12 in inflammatory process in the airways were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12 in mouse airways. Hence, we have demonstrated that this instillation induced a severe inflammatory cell recruitment characterized by an early accumulation of neutrophils correlated with an increase in proinflammatory cytokines and in gelatinases and then by a relatively stable recruitment of macrophages in the lungs over a period of ten days. Another recent study suggests that resident alveolar macrophages and recruited neutrophils are not involved in the delayed macrophage recruitment. However, epithelial cells could be one of the main targets of rhMMP-12 in our model. We have also reported that a corticoid, dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP inhibitor, marimastat could reverse some of these inflammatory events. These data indicate that our rhMMP-12 model could mimic some of the inflammatory features observed in COPD patients and could be used for the pharmacological evaluation of new anti-inflammatory treatment. In this review, data demonstrating the involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be summarized.

  20. Perawatan Pulpa Gigi Sulung Disertai Abses Dento Alveolar

    OpenAIRE

    Nasution, Nurasiah Adita

    2008-01-01

    Abses dento alveolar adalah kumputan pus yang berada pada tulang alveolar sekitar apeks gigi akibat kematian pulpa. Matinya pulpa dapat disebabkan bakteri, trauma, iritasi mekanis, termis maupun kimiawi. Pengaruh bakteri merupakan penyebab kerusakan jaringan pulpa yang terbesar. Perluasan infeksi ke dalam jaringan periapikal dapat melalui foramen apikalke jaringan periodontal sehingga terjadi inflarnasi. Bila virulensi bakteri meningkat disertai rendahnya pertahanan tubuh penderita dapat ...

  1. Alveolar pressure during high-frequency jet ventilation

    NARCIS (Netherlands)

    A.J. van Vught (Adrianus); A. Versprille (Adrian); J.R.C. Jansen (Jos)

    1990-01-01

    textabstractWe studied the influence of ventilatory frequency (1-5 Hz), tidal volume, lung volume and body position on the end-expiratory alveolar-to-tracheal pressure difference during high-frequency jet ventilation (HFJV) in Yorkshire piglets. The animals were anesthetized and paralysed. Alveolar

  2. Post-neonatal drop in alveolar SP-A expression

    DEFF Research Database (Denmark)

    Stray-Pedersen, Arne; Vege, Ashild; Stray-Pedersen, Asbjorg;

    2008-01-01

    was developed enabling semi-quantitative estimation of staining intensity and distribution. RESULTS: SP-A was detected in the terminal bronchioles and alveolar spaces of fetuses >35 weeks gestation. The intra-alveolar SP-A expression increased in the perinatal period followed by a marked drop in infants aged...

  3. Anaesthetic management of bilateral alveolar proteinosis for bronchopulmonary lavage.

    OpenAIRE

    Dixit R; Chaudhari L; Mahashur A

    1998-01-01

    The most hazardous manifestation of pulmonary alveolar proteinosis is progressive hypoxia for which bronchopulmonary lavage (BPL) is the single most effective treatment. Unfortunately this procedure under general anesthesia itself increases the risk of hypoxia due to the need for one lung ventilation. It was therefore considered interesting to report the successful anaesthetic management of a patient with pulmonary alveolar proteinosis for Bronchopulmonary lavage.

  4. Tongue-Palate Contact of Perceptually Acceptable Alveolar Stops

    Science.gov (United States)

    Lee, Alice; Gibbon, Fiona E.; O'Donovan, Cliona

    2013-01-01

    Increased tongue-palate contact for perceptually acceptable alveolar stops has been observed in children with speech sound disorders (SSD). This is a retrospective study that further investigated this issue by using quantitative measures to compare the target alveolar stops /t/, /d/ and /n/ produced in words by nine children with SSD (20 tokens of…

  5. DAP12 expression in lung macrophages mediates ischemia/reperfusion injury by promoting neutrophil extravasation.

    Science.gov (United States)

    Spahn, Jessica H; Li, Wenjun; Bribriesco, Alejandro C; Liu, Jie; Shen, Hua; Ibricevic, Aida; Pan, Jie-Hong; Zinselmeyer, Bernd H; Brody, Steven L; Goldstein, Daniel R; Krupnick, Alexander S; Gelman, Andrew E; Miller, Mark J; Kreisel, Daniel

    2015-04-15

    Neutrophils are critical mediators of innate immune responses and contribute to tissue injury. However, immune pathways that regulate neutrophil recruitment to injured tissues during noninfectious inflammation remain poorly understood. DAP12 is a cell membrane-associated protein that is expressed in myeloid cells and can either augment or dampen innate inflammatory responses during infections. To elucidate the role of DAP12 in pulmonary ischemia/reperfusion injury (IRI), we took advantage of a clinically relevant mouse model of transplant-mediated lung IRI. This technique allowed us to dissect the importance of DAP12 in tissue-resident cells and those that infiltrate injured tissue from the periphery during noninfectious inflammation. Macrophages in both mouse and human lungs that have been subjected to cold ischemic storage express DAP12. We found that donor, but not recipient, deficiency in DAP12 protected against pulmonary IRI. Analysis of the immune response showed that DAP12 promotes the survival of tissue-resident alveolar macrophages and contributes to local production of neutrophil chemoattractants. Intravital imaging demonstrated a transendothelial migration defect into DAP12-deficient lungs, which can be rescued by local administration of the neutrophil chemokine CXCL2. We have uncovered a previously unrecognized role for DAP12 expression in tissue-resident alveolar macrophages in mediating acute noninfectious tissue injury through regulation of neutrophil trafficking.

  6. Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages

    Directory of Open Access Journals (Sweden)

    Dagmar A. Kuhn

    2014-09-01

    Full Text Available Precise knowledge regarding cellular uptake of nanoparticles is of great importance for future biomedical applications. Four different endocytotic uptake mechanisms, that is, phagocytosis, macropinocytosis, clathrin- and caveolin-mediated endocytosis, were investigated using a mouse macrophage (J774A.1 and a human alveolar epithelial type II cell line (A549. In order to deduce the involved pathway in nanoparticle uptake, selected inhibitors specific for one of the endocytotic pathways were optimized regarding concentration and incubation time in combination with fluorescently tagged marker proteins. Qualitative immunolocalization showed that J774A.1 cells highly expressed the lipid raft-related protein flotillin-1 and clathrin heavy chain, however, no caveolin-1. A549 cells expressed clathrin heavy chain and caveolin-1, but no flotillin-1 uptake-related proteins. Our data revealed an impeded uptake of 40 nm polystyrene nanoparticles by J774A.1 macrophages when actin polymerization and clathrin-coated pit formation was blocked. From this result, it is suggested that macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play a crucial role. The uptake of 40 nm nanoparticles in alveolar epithelial A549 cells was inhibited after depletion of cholesterol in the plasma membrane (preventing caveolin-mediated endocytosis and inhibition of clathrin-coated vesicles (preventing clathrin-mediated endocytosis. Our data showed that a combination of several distinguishable endocytotic uptake mechanisms are involved in the uptake of 40 nm polystyrene nanoparticles in both the macrophage and epithelial cell line.

  7. Cytotoxic effects of four types of welding fumes on macrophages in vitro: a comparative study.

    Science.gov (United States)

    Pasanen, J T; Gustafsson, T E; Kalliomäki, P L; Tossavainen, A; Järvisalo, J O

    1986-01-01

    The effects of fume particles given off by the manual metal arc (MMA) and metal inert gas (MIG) welding of stainless steel (SS) and mild steel (MS) were studied on rat alveolar macrophage cultures in vitro. The fumes were generated by welding, and particulate material obtained was collected on membrane filters. The macrophage cultures were exposed to the total dust and to its water-insoluble fractions. Cell variability and the release of both lactate dehydrogenase and one lysosomal enzyme from the cells to the medium were measured after an exposure period of 24 h. The cytotoxic control dust was DQ 12 quartz, and the inert control dust was pure titanium dioxide. According to the parameters studied, SS/MMA and MS/MMA welding fumes were cytotoxic to rat alveolar macrophages. The cytotoxic effect of SS/MMA welding fumes decreased after the samples had been washed with phosphate-buffered salt solution. The MIG welding fumes of SS and MS had markedly smaller effects on the cells. Diluted solutions of potassium chromate were also tested in order to investigate its role in the cytotoxicity of SS/MMA welding fumes. The results suggest that hexavalent chromium may be responsible for the cytotoxicity of SS/MMA. PMID:3701879

  8. Host lung immunity is severely compromised during tropical pulmonary eosinophilia: role of lung eosinophils and macrophages.

    Science.gov (United States)

    Sharma, Pankaj; Sharma, Aditi; Vishwakarma, Achchhe Lal; Agnihotri, Promod Kumar; Sharma, Sharad; Srivastava, Mrigank

    2016-04-01

    Eosinophils play a central role in the pathogenesis of tropical pulmonary eosinophilia, a rare, but fatal, manifestation of filariasis. However, no exhaustive study has been done to identify the genes and proteins of eosinophils involved in the pathogenesis of tropical pulmonary eosinophilia. In the present study, we established a mouse model of tropical pulmonary eosinophilia that mimicked filarial manifestations of human tropical pulmonary eosinophilia pathogenesis and used flow cytometry-assisted cell sorting and real-time RT-PCR to study the gene expression profile of flow-sorted, lung eosinophils and lung macrophages during tropical pulmonary eosinophilia pathogenesis. Our results show that tropical pulmonary eosinophilia mice exhibited increased levels of IL-4, IL-5, CCL5, and CCL11 in the bronchoalveolar lavage fluid and lung parenchyma along with elevated titers of IgE and IgG subtypes in the serum. Alveolar macrophages from tropical pulmonary eosinophilia mice displayed decreased phagocytosis, attenuated nitric oxide production, and reduced T-cell proliferation capacity, and FACS-sorted lung eosinophils from tropical pulmonary eosinophilia mice upregulated transcript levels of ficolin A and anti-apoptotic gene Bcl2,but proapoptotic genes Bim and Bax were downregulated. Similarly, flow-sorted lung macrophages upregulated transcript levels of TLR-2, TLR-6, arginase-1, Ym-1, and FIZZ-1 but downregulated nitric oxide synthase-2 levels, signifying their alternative activation. Taken together, we show that the pathogenesis of tropical pulmonary eosinophilia is marked by functional impairment of alveolar macrophages, alternative activation of lung macrophages, and upregulation of anti-apoptotic genes by eosinophils. These events combine together to cause severe lung inflammation and compromised lung immunity. Therapeutic interventions that can boost host immune response in the lungs might thus provide relief to patients with tropical pulmonary eosinophilia. PMID

  9. Treatment to pulmonary alveolar proteinosis with total bronchoalveolar lavage

    International Nuclear Information System (INIS)

    The pulmonary alveolar proteinosis is a rare disease with variable course and characterized by the accumulation of surfactant in the alveoli. By the treatment it was used the alveolar lavage with good results. We present the experience accumulated in the Las Americas clinic of Medellin city with the treatment of three patients with diagnosis of pulmonary alveolar proteinosis by alveolar lavage. We realized seven lavages, two of them bilateral and sequential. We didn't 't have important complications and in all cases we got good clinical and physiological results. Two patients had relapsed six and seven months after the first lavage and they needed a second lavage. We conclude that the pulmonary lavage is a secure and effective procedure in the treatment of the pulmonary alveolar proteinosis and the modality of bilateral sequential lavage is a good alternative and less expensive

  10. Contemporary Approaches in the Repair of Alveolar Clefts

    Directory of Open Access Journals (Sweden)

    Ufuk Tatli

    2014-08-01

    Full Text Available Cleft lip and palate is one of the most common craniofacial anomalies. The repair of the alveolar clefts is an important part of the treatment for patients with cleft lip and palate. The treatment concepts of alveolar bone grafting are still controversial. The corresponding controversial issues are; timing of alveolar bone grafting, graft materials, and timing of the orthodontic expansion. In the present article, aforementioned controversial issues and contemporary treatment modalities of the maxillary alveolar clefts were reviewed in the light of current literature. In conclusion, the most suitable time for alveolar bone grafting is mixed dentition period. Grafting procedure may be performed in the early or late phases of this period depending on some clinical features. Adjunct orthodontic expansion procedures should be performed before and/or after grafting depending on the patient's current features. [Archives Medical Review Journal 2014; 23(4.000: 563-574

  11. Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss

    Institute of Scientific and Technical Information of China (English)

    Ujjal K Bhawal; Nobushiro Hamada; Ikuo Nasu; Hirohisa Arakawa; Koh Shibutani; Hye-Jin Lee; Kazumune Arikawa; Michiharu Shimosaka; Masatoshi Suzuki; Toshizo Toyama; Takenori Sato; Ryota Kawamata; Chieko Taguchi

    2015-01-01

    Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte/macrophage lineage precursors. Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases. Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride (NaF) on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. NaF strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of cathepsin K, interleukin (IL)-1b, matrix metalloproteinase 9 (MMP9), and tartrate-resistant acid phosphatase, which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti-osteoclastogenic effect, NaF inhibited osteoclast formation caused by the differentiation factor RANKL (receptor activator of nuclear factor kB ligand) and macrophage colony-stimulating factor (M-CSF). The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells (NFAT) c1 was also abrogated by NaF. Taken together, our data demonstrate that NaF inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATc1, ultimately leading to the suppressed expression of cathepsin K and MMP9. The in vivo effect of NaF on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of NaF for treating periodontal diseases.

  12. Rv3351c, a Mycobacterium tuberculosis gene that affects bacterial growth and alveolar epithelial cell viability.

    Science.gov (United States)

    Pavlicek, Rebecca L; Fine-Coulson, Kari; Gupta, Tuhina; Quinn, Frederick D; Posey, James E; Willby, Melisa; Castro-Garza, Jorge; Karls, Russell K

    2015-12-01

    Despite the interactions known to occur between various lower respiratory tract pathogens and alveolar epithelial cells (AECs), few reports examine factors influencing the interplay between Mycobacterium tuberculosis bacilli and AECs during infection. Importantly, in vitro studies have demonstrated that the M. tuberculosis hbha and esxA gene products HBHA and ESAT6 directly or indirectly influence AEC survival. In this report, we identify Rv3351c as another M. tuberculosis gene that impacts the fate of both the pathogen and AEC host. Intracellular replication of an Rv3351c mutant in the human AEC type II pneumocyte cell line A549 was markedly reduced relative to the complemented mutant and parent strain. Deletion of Rv3351c diminished the release of lactate dehydrogenase and decreased uptake of trypan blue vital stain by host cells infected with M. tuberculosis bacilli, suggesting attenuated cytotoxic effects. Interestingly, an isogenic hbha mutant displayed reductions in AEC killing similar to those observed for the Rv3351c mutant. This opens the possibility that multiple M. tuberculosis gene products interact with AECs. We also observed that Rv3351c aids intracellular replication and survival of M. tuberculosis in macrophages. This places Rv3351c in the same standing as HBHA and ESAT6, which are important factors in AECs and macrophages. Defining the mechanism(s) by which Rv3351c functions to aid pathogen survival within the host may lead to new drug or vaccine targets.

  13. Autophagy deficiency in macrophages enhances NLRP3 inflammasome activity and chronic lung disease following silica exposure.

    Science.gov (United States)

    Jessop, Forrest; Hamilton, Raymond F; Rhoderick, Joseph F; Shaw, Pamela K; Holian, Andrij

    2016-10-15

    Autophagy is an important metabolic mechanism that can promote cellular survival following injury. The specific contribution of autophagy to silica-induced inflammation and disease is not known. The objective of these studies was to determine the effects of silica exposure on the autophagic pathway in macrophages, as well as the general contribution of autophagy in macrophages to inflammation and disease. Silica exposure enhanced autophagic activity in vitro in Bone Marrow derived Macrophages and in vivo in Alveolar Macrophages isolated from silica-exposed mice. Impairment of autophagy in myeloid cells in vivo using Atg5(fl/fl)LysM-Cre(+) mice resulted in enhanced cytotoxicity and inflammation after silica exposure compared to littermate controls, including elevated IL-18 and the alarmin HMGB1 in the whole lavage fluid. Autophagy deficiency caused some spontaneous inflammation and disease. Greater silica-induced acute inflammation in Atg5(fl/fl)LysM-Cre(+) mice correlated with increased fibrosis and chronic lung disease. These studies demonstrate a critical role for autophagy in suppressing silica-induced cytotoxicity and inflammation in disease development. Furthermore, this data highlights the importance of basal autophagy in macrophages and other myeloid cells in maintaining lung homeostasis.

  14. Activation of a distinct subpopulation of pulmonary macrophages following exposure to biological response modifiers.

    Science.gov (United States)

    Drath, D B; Do, C; Burd, T; Hong, L L

    1994-03-01

    A distinct subpopulation of tissue-associated pulmonary macrophages (TAPM) displayed tumoricidal activity towards syngeneic and xenogeneic targets following in vitro incubation with N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP). This subpopulation, as well as, the predominant population of freely lavagable alveolar macrophages destroyed allogeneic targets following a similar incubation with either 6-0-stearoyl MDP (S-MDP) or recombinant interferon-gamma (IFN-gamma). IFN-gamma-induced in vivo tumoricidal activation of both populations of pulmonary macrophage was most effective when delivered either intravenously or via osmotic minipump infusion and least effective when administered by direct intratracheal instillation. The separate populations also displayed in vivo activation in response to liposome-encapsulated i.v. administered S-MDP. Under comparable conditions, IFN-alpha was not nearly as effective. Metabolic activation of TAPM, assessed by the release of increased levels of superoxide free radicals during phagocytosis, occurred following 24 hr exposure to S-MDP or lipopolysaccharide. Incorporation of these agents into multilamellar vesicle liposomes further augmented the release of superoxide observed at 24 hrs. Our results collectively demonstrated that a subpopulation of lung macrophage, a tissue-associated pulmonary macrophage, may be activated to a tumoricidal state and to release pronounced levels of oxygen free radicals following either in vitro or in situ treatment with several biological response modifiers. PMID:8194852

  15. Chronic Exposure to Water-Pipe Smoke Induces Alveolar Enlargement, DNA Damage and Impairment of Lung Function

    Directory of Open Access Journals (Sweden)

    Abderrahim Nemmar

    2016-03-01

    Full Text Available Background/Aim: Epidemiological evidence indicates that water-pipe smoking (WPS adversely affects the respiratory system. However, the mechanisms underlying its effects are not well understood. Recent experimental studies reported the occurrence of lung inflammation and oxidative stress following acute and subacute exposure to WPS. Here, we wanted to verify the extent of inflammation and oxidative stress in mice chronically-exposed to WPS and to evaluate, for the first time, its effect on alveolar injury and DNA damage and their association with impairment of lung function. Methods: Mice were nose-only exposed to mainstream WPS (30 min/day; 5 days/week for 6 consecutive months. Control mice were exposed using the same protocol to atmospheric air only. At the end of the exposure period, several respiratory parameters were assessed. Results: In bronchoalveolar lavage fluid, WPS increased neutrophil and lymphocyte numbers, lactate dehydrogenase, myeloperoxidase and matrix metallopeptidase 9 activities, as well as several proinflammatory cytokines. In lung tissue, lipid peroxidation, reactive oxygen species, superoxide dismutase activity and reduced glutathione were all increased by WPS exposure. Along with oxidative stress, WPS exposure significantly increased lung DNA damage index. Histologically the lungs of WPS-exposed mice had foci of mixed inflammatory cells infiltration in the interalveolar interstitium which consisted of neutrophils, lymphocytes and macrophages. Interestingly, we found dilated alveolar spaces and alveolar ducts with damaged interalveolar septae, and impairment of lung function following WPS exposure. Conclusion: We show the persistence of lung inflammation and oxidative stress in mice chronically-exposed to WPS and demonstrate, for the first time, the occurrence of DNA damage and enlargement of alveolar spaces and ducts associated with impairment of lung function. Our findings provide novel mechanistic elucidation for the

  16. Neonatal malnutrition programs the oxidant function of macrophages in response to Candida albicans.

    Science.gov (United States)

    Costa, Thacianna Barreto Da; Morais, Natália Gomes De; Pedrosa, Amanda Lúcia F; De Albuquerque, Suênia Da Cunha G; De Castro, Maria Carolina A B; Pereira, Valéria Rêgo A; Cavalcanti, Milena De Paiva; De Castro, Célia Maria M B

    2016-06-01

    Experimental maternal nutrition restriction models are used to investigate short or long-term consequences of nutritional deficiency on puppies' growth. By assuming that the immune function is directly related to host's nutritional status, the current study aims to investigate the effects of neonatal malnutrition on oxidative stress and on the cell death of the alveolar macrophage after in vitro infection by Candida albicans. Wistar rats were suckled by mothers fed on diets containing 17% protein (Nourished group) or 8% protein (Malnourished group) in the current assay. Both groups received the standard diet used in the vivarium until adulthood, after weaning. The results showed that the offspring from mothers fed on low-protein diet presented lower body weight from 5 days of life on. Their low weight remained until adulthood when it was compared to that of rats in the nourished group. Superoxide and nitric oxide production was lower in malnourished animals and it was accompanied by low inducible nitric oxide synthase gene expression levels in systems in which the alveolar macrophages were challenged by immunogenic stimulus. No significant differences were observed in comparisons performed between the nourished and malnourished groups in any of the analyzed cell viability (apoptosis/necrosis) parameters. The fungal inoculum-stimulated system induced higher oxidative stress and cell death by necrosis. The current study demonstrated that dietary restriction during lactation alters the oxidant function of alveolar macrophages in puppies; It happens from the gene transcription step to the release of mediators, thus compromising the host's defenses against Candida albicans. It raises the possibility that Candida albicans may cease to be a commensal fungus to become a pathogen in offspring that have suffered nutritional deficiency during critical developmental periods, due to impaired immune responses. PMID:27001703

  17. Recent advances in alveolar biology: Evolution and function of alveolar proteins☆

    OpenAIRE

    Orgeig, Sandra; Hiemstra, Pieter S.; Edwin J A Veldhuizen; Casals, Cristina; Clark, Howard W.; Haczku, Angela; Knudsen, Lars; Possmayer, Fred

    2010-01-01

    This review is focused on the evolution and function of alveolar proteins. The lung faces physical and environmental challenges, due to changing pressures/volumes and foreign pathogens, respectively. The pulmonary surfactant system is integral in protecting the lung from these challenges via two groups of surfactant proteins – the small molecular weight hydrophobic SPs, SP-B and -C, that regulate interfacial adsorption of the lipids, and the large hydrophilic SPs, SP-A and -D, which are surfa...

  18. Hemorragia alveolar associada a nefrite lúpica Alveolar hemorrhage associated with lupus nephritis

    Directory of Open Access Journals (Sweden)

    Ricardo Henrique de Oliveira Braga Teixeira

    2003-12-01

    Full Text Available Hemorragia alveolar, como causa de insuficiência respiratória, é pouco freqüente, com diversas etiologias possíveis. Entre elas, o lúpus eritematoso sistêmico, que se apresenta geralmente como síndrome pulmão-rim, possui alta morbimortalidade. Acredita-se que a patogênese da microangiopatia, tanto renal como pulmonar, esteja associada ao depósito de imunocomplexos, que ativariam as vias de apoptose celular. Relatam-se dois casos de pacientes com nefrite lúpica que evoluíram com hemorragia alveolar associada à insuficiência respiratória necessitando de ventilação mecânica com evoluções totalmente distintas frente às terapias farmacológicas. O achado de anticorpos antimembrana basal em um dos casos evidencia a multiplicidade de mecanismos fisiopatológicos possivelmente envolvidos, que poderiam justificar as respostas heterogêneas frente aos tratamentos disponíveis.Alveolar hemorrhage leading to respiratory failure is uncommon. Various etiologies have been reported, including systemic lupus erythematosus, which generally presents as pulmonary-renal syndrome. It is believed that the pathogenesis of microangiopathy is related to deposits of immune complexes that lead to activation of cellular apoptosis. The authors report two cases of alveolar hemorrhage and respiratory failure, both requiring mechanical ventilation. The two cases had opposite outcomes after pharmacological therapy. The presence of anti-glomerular basement membrane antibodies in one of the cases demonstrates the multiplicity of physiopathological mechanisms that may be involved. This multiplicity of mechanisms provides a possible explanation for the heterogeneous responses to the available treatments.

  19. CT diagnosis of pulmonary alveolar microlithiasis

    International Nuclear Information System (INIS)

    Purpose: To study the CT findings and evaluate the value of CT in the diagnosis of pulmonary alveolar microlithiasis (PAM). Methods: The CT findings of 9 cases of PAM proved by lung biopsy or clinical diagnosis were retrospectively analysed. Results: On conventional CT, pulmonary window revealed widespread intraalveolar calcifications of both lungs concentrating in the subpleural parenchyma of the middle and lower lobes. The CT value of microliths ranged from 200 to 400 HU, usually combined with pulmonary emphysema and interstitial fibrosis; Mediastinal window showed linear calcifications along pleura or scattered punctate calcifications in the concentrated area of microliths looking like flame or white line in the medial border. On HRCT, pulmonary window revealed diffuse ground-glass appearance, nodules of different sizes, more microliths along the bronchovesicular bundles and thickening of lobule septa. Conclusion: CT, especially HRCT, can better demonstrate pathological features and stage of PAM, playing an important role in diagnosis and differential diagnosis

  20. Computed tomographic appearances of pulmonary alveolar proteinosis

    International Nuclear Information System (INIS)

    We evaluated longitudinal changes in chest CT images in six cases (5 males and one female, age: 35-57 yr) of pulmonary alveolar proteinosis treated with bronchopulmonary lavage. Chest CT images on admission showed a mixed pattern of air-space consolidation and reticular or reticulonodular shadows in most cases and showed a peripheral clear zone in all cases. These shadows gradually diminished after bronchopulmonary lavage. Some cases revealed early improvement in the hilar zone while others had equal improvement in all lung lesions. In one case, consolidation was changed into reticular shadows by treatment. Previous reports have indicated that 'interstitial shadows which disappeared with lavage' reflect edematous thickening of interlobular septa. However, our longitudinal evaluation suggests that interstitial shadows on CT images may reflect not only real interstitial infiltration but also inhomogeneous distribution of intralobular deposits. (author)

  1. Computed tomographic appearances of pulmonary alveolar proteinosis

    Energy Technology Data Exchange (ETDEWEB)

    Takiguchi, Yasuo; Uchiyama, Takashi; Nagao, Keiichi; Kuriyama, Takayuki (Chiba Univ. (Japan). School of Medicine); Fujita, Akira; Hashizume, Ikko

    1994-03-01

    We evaluated longitudinal changes in chest CT images in six cases (5 males and one female, age: 35-57 yr) of pulmonary alveolar proteinosis treated with bronchopulmonary lavage. Chest CT images on admission showed a mixed pattern of air-space consolidation and reticular or reticulonodular shadows in most cases and showed a peripheral clear zone in all cases. These shadows gradually diminished after bronchopulmonary lavage. Some cases revealed early improvement in the hilar zone while others had equal improvement in all lung lesions. In one case, consolidation was changed into reticular shadows by treatment. Previous reports have indicated that 'interstitial shadows which disappeared with lavage' reflect edematous thickening of interlobular septa. However, our longitudinal evaluation suggests that interstitial shadows on CT images may reflect not only real interstitial infiltration but also inhomogeneous distribution of intralobular deposits. (author).

  2. Epidemiology of human alveolar echinococcosis in China.

    Science.gov (United States)

    Craig, Philip S

    2006-01-01

    Globally human alveolar echinococcosis (AE) is a rare zoonotic helminthic disease confined to the Northern Hemisphere as sporadic infections in rural populations, principally in some areas of North America, west-central Europe, the Near East, Siberia, Central Asia, Japan and China. In China the first human cases were reported from western regions in the 1960s, but most hospital records remain fragmented and inadequate. From the mid-1990s mass screening surveys using portable ultrasound scanners recorded higher prevalences (up to 6% by county) than in any other areas of the world with some village rates as high as 15%. Risk factors identified for AE cases included ethnicity, sex, age and occupation. The role of the dog in transmission of Echinococcus multilocularis to humans now appears to be significant and may be one of the most important risk factor, in combination with landscape/land-use features conducive to maintaining wildlife host populations. PMID:16338167

  3. Imaging features of alveolar soft part sarcoma

    Institute of Scientific and Technical Information of China (English)

    Teng Jin; Ping Zhang Co-first author; Xiaoming Li

    2015-01-01

    Objective The aim of this study was to analyze the imaging features of alveolar soft part sarcoma (ASPS). Methods The imaging features of 11 cases with ASPS were retrospectively analyzed. Results ASPS mainly exhibited an isointense or slightly high signal intensity on T1-weighted imaging (T1WI), and a mixed high signal on T2-weighted imaging (T2WI). ASPS was partial, with rich tortuous flow voids, or “line-like” low signal septa. The essence of the mass was heterogeneous enhancement. The 1H-MRS showed a slight choline peak at 3.2 ppm. Conclusion The wel-circumscribed mass and blood voids, combined with “line-like” low signals play a significant role in diagnosis. The choline peak and the other signs may be auxiliary diagnoses.

  4. L-Fucose-terminated glycoconjugates are recognized by pinocytosis receptors on macrophages.

    OpenAIRE

    Shepherd, V L; Lee, Y.C.; Schlesinger, P H; Stahl, P D

    1981-01-01

    125I-Labeled L-fucose-albumin complex and rat preputial beta-glucuronidase are rapidly cleared from plasma after intravenous infusion. L-Fucose-albumin retards the plasma clearance of beta-glucuronidase whereas D-fucose-albumin is inactive. In vitro, 125I-labeled L-fucose-albumin is taken up into rat or rabbit alveolar macrophages by receptor-mediated pinocytosis. Uptake (37 degrees C) is time-dependent, is saturable with increasing ligand concentration (Kuptake = 4.4 X 10(-8) M), and require...

  5. [Distraction osteogenesis of deficient alveolar bone prior to dental rehabilitation].

    Science.gov (United States)

    Shilo, D; Emodi, O; Aizenbud, D; Rachmiel, A

    2015-07-01

    Implant supported rehabilitation has become very common in treatment plans nowadays, yet many patients lack the vertical and horizontal bone dimensions required for endosseous implant insertion. Distraction osteogenesis is a technique in which bone is generated by progressive elongation of two bone fragments following an osteotomy or corticotomy. Distraction osteogenesis of the alveolar ridge as a treatment modality in implant dentistry is a very useful technique that allows for adequate bone formation suitable for implant insertion. Alveolar distraction can be unidirectional, bidirectional, multidirectional or horizontal. Alveolar distraction osteogenesis can be performed by using intraosseous distraction devices, intraosseous distraction implants or by extraosseous devices which are the most prevalent today. Distraction osteogenesis has many advantages such as gradual lengthening of the bone with no need for an autogenous bone graft and lack of the associated donor site morbidity as well as distraction of the surrounding soft tissue together with the transported bone. One of the major challenges when using alveolar distraction osteogenesis is controlling the vector of distraction, this problem should be further addressed in future researches. We describe different methods for alveolar distraction osteogenesis, including the surgical procedure, latency period, lengthening and consolidation period. We also discuss the advantages, disadvantages and complications of the method. In this manuscript a case of mandibular alveolar deficiency following mandibular fracture and loss of teeth and the alveolar bone is presented. This patient was treated by alveolar distraction osteogenesis with excellent results. This patient was later rehabilitated . using endosseous implants as demonstrated by radiographs. Alveolar distraction osteogenesis provides a method to regain both hard tissue and soft tissue without additional grafting and is an efficient modality in cases of medium

  6. Upper Alveolar Ridge in Edentulous Patients and Caldwell Luc Surgery

    OpenAIRE

    Ashok Murthy, V.; Mahendra Kumar, R.

    2012-01-01

    The aim of this study is to understand the upper alveolar ridge changes and its impact on Caldwell Luc surgery, in a patient papulation from a Medical College Hospital. We undertook a study to measure the thickness of upper alveolar ridge in edentulous and edentulous patients, to know the difference between the two and its effects on Caldwell Luc surgery. The finding of the study led us to conclude that the upper alveolar ridge is quite thin in edentulous patients and requires care while scra...

  7. Crazy paving radiography finding in asymptomatic pulmonary alveolar proteinosis.

    Science.gov (United States)

    Choi, Young Rak; Chang, You-Jin; Kim, Si Wook; Choe, Kang Hyeon; Lee, Ki Man; An, Jin-Young

    2015-06-01

    Pulmonary alveolar proteinosis is a rare disorder characterized by alveolar accumulation of surfactant phospholipids and protein components. The symptoms and prognosis are extremely variable. Bronchoalveolar lavage fluid and/or transbronchial lung biopsy are useful for diagnosis; surgical lung biopsy is often unnecessary but useful in the focal involvement. We report a case of pulmonary alveolar proteinosis in a 50-year-old woman, confirmed by a video-assisted thoracoscopic surgery biopsy from the initial focal involvement, with normal bronchoalveolar lavage and transbronchial lung biopsy findings. PMID:25182335

  8. Laser-matter interaction studies at Centre d'Etudes de Limeil

    International Nuclear Information System (INIS)

    A review is made of the laser-matter interaction and implosion experiments carried out at Centre d'Etudes de Limeil with the two following neodymium glass lasers; the monobeam 50 J - 1ns P102 laser for the interaction with foils and the eight beam 400 J - 0.5ns OCTAL laser for the implosion of glass microballoons

  9. CFTR is required for maximal transepithelial liquid transport in pig alveolar epithelia

    OpenAIRE

    Li, Xiaopeng; Comellas, Alejandro P.; Karp, Philip H.; Ernst, Sarah E.; Moninger, Thomas O.; Gansemer, Nicholas D.; Taft, Peter J.; Pezzulo, Alejandro A; Michael V Rector; Rossen, Nathan; Stoltz, David A.; McCray, Paul B.; Welsh, Michael J.; Zabner, Joseph

    2012-01-01

    A balance between alveolar liquid absorption and secretion is critical for maintaining optimal alveolar subphase liquid height and facilitating gas exchange in the alveolar space. However, the role of cystic fibrosis transmembrane regulator protein (CFTR) in this homeostatic process has remained elusive. Using a newly developed porcine model of cystic fibrosis, in which CFTR is absent, we investigated ion transport properties and alveolar liquid transport in isolated type II alveolar epitheli...

  10. The role of synthetic biomaterials in resorptive alveolar bone regeneration

    Directory of Open Access Journals (Sweden)

    Kaličanin Biljana M.

    2007-01-01

    Full Text Available The alveolar bone tissue resorption defect has a significant role in dentistry. Because of the bone tissue deficit developed by alveolar resorption, the use of synthetic material CP/PLGA (calcium-phosphate/polylactide-co-gliycolide composite was introduced. Investigations were performed on rats with artificially produced resorption of the mandibular bone. The results show that the best effect on alveolar bone were attained by using nano-composite implants. The effect of the nanocomposite was ascertained by determining the calcium and phosphate content, as a basis of the hydroxyapatite structure. The results show that synthetic CP/PLGA nanocomposite alleviate the rehabilitation of weakened alveolar bone. Due to its osteoconductive effect, CP/PLGA can be the material of choice for bone substitution in the future.

  11. Alveolar proteinosis lung lavage using partial cardiopulmonary bypass.

    OpenAIRE

    Freedman, A P; Pelias, A; Johnston, R F; Goel, I P; Hakki, H I; Oslick, T; Shinnick, J P

    1981-01-01

    An adult case of pulmonary alveolar proteinosis presented with an arterial oxygen tension of 27 mmHg (3.6 kPa) while breathing air. Dangerous hypoxaemia during lung lavage was avoided by using partial cardiopulmonary bypass.

  12. Pulmonary Alveolar Proteinosis: A Rare Cause of Respiratory Failure.

    Science.gov (United States)

    Munir, Zeeshan; Khosa, Muhammad Zeeshan; Qazi, Muhammad Yaqoob

    2015-07-01

    Pulmonary Alveolar Proteinosis (PAP) is a rare syndrome in the paediatric age group and characterized by intra-alveolar accumulation of proteinaceous phospholipid-laden material called surfactant. The diagnosis is made by High Resolution Computed Tomography (HRCT) chest which shows characteristic crazy paving appearance and diagnosis confirmed by Bronchoalveolar Lavage (BAL). We report two cases. First was a 9-month old infant who presented with respiratory distress and peripheral cyanosis since birth. He was diagnosed on High Resolution Computed Tomography (HRCT) chest as a case of pulmonary alveolar proteinosis and broncho-alveolar lavage confirmed his diagnosis. Second case was a 10-year old female child who had a history of repeated chest infections for 5 years and now presented with cough and respiratory distress for 45 days. She was also diagnosed on HRCT chest but unfortunately she died before bronchoalveolar lavage. PMID:26208564

  13. Alveolar lymphangioma in infants: report of two cases.

    LENUS (Irish Health Repository)

    FitzGerald, Kirsten

    2009-06-01

    The alveolar lymphangioma is a benign but relatively rare condition found only in the oral cavities of black infants. Dentists practising in Ireland may be unaware of this condition due to its racial specificity. This paper presents two case reports of multiple alveolar lymphangiomas found in black infants in a children\\'s hospital in Ireland. The epidemiology, aetiology, clinical presentation, histology, and management options are discussed. The photographs should aid the practitioner in recognising these lesions.

  14. Dynamics of surfactant release in alveolar type II cells

    OpenAIRE

    Haller, Thomas; Ortmayr, Jörg; Friedrich, Franz; Völkl, Harald; Dietl, Paul

    1998-01-01

    Pulmonary surfactant, secreted via exocytosis of lamellar bodies (LB) by alveolar type II (AT II) cells, maintains low alveolar surface tension and is therefore essential for normal lung function. Here we describe real-time monitoring of exocytotic activity in these cells by visualizing and quantifying LB fusion with the plasma membrane (PM). Two approaches were used. First, fluorescence of LysoTracker Green DND-26 (LTG) in LB disappeared when the dye was released after exocytosis. Second, ph...

  15. Identification of a cell membrane protein that binds alveolar surfactant.

    OpenAIRE

    Strayer, D. S.

    1991-01-01

    Alveolar surfactants are complex mixtures of proteins and phospholipids produced by type II alveolar cells and responsible for lowering pulmonary surface tension. The process by which surfactant is produced and exported and by which its production by pulmonary cells is regulated are not well understood. This study was designed to identify a cellular receptor for surfactant constituents. To do so, monoclonal anti-idiotypic antibodies directed against antibodies to porcine and rabbit surfactant...

  16. Is alveolar cleft reconstruction still controversial? (Review of literature)

    OpenAIRE

    Seifeldin, Sameh A.

    2015-01-01

    Cleft lip and palate (CL/P) is a frequent congenital malformation that manifests in several varieties including unilateral or bilateral and complete or incomplete. Alveolar cleft reconstruction remains controversial with regard to timing, graft materials, surgical techniques, and methods of evaluation. Many studies have been conducted addressing these points to develop an acceptable universal protocol for managing CL/P. The primary goal of alveolar cleft reconstruction in CL/P patients is to ...

  17. Familial occurrence of pulmonary alveolar microlithiasis in 3-siblings

    International Nuclear Information System (INIS)

    Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown etiology characterized by intra-alveolar calcium deposits. More than 500 cases were reported in the literature. The disorder affects people at every age beginning from the early childhood. It occurs probably as a result of autosomal recessive transmission. Familial occurrence is often found with family history of the disease being present in up to 50% of the reported cases. We report PAM in 3 siblings. (author)

  18. Alveolar lymphangioma in infants: report of two cases.

    LENUS (Irish Health Repository)

    FitzGerald, Kirsten

    2012-02-01

    The alveolar lymphangioma is a benign but relatively rare condition found only in the oral cavities of black infants. Dentists practising in Ireland may be unaware of this condition due to its racial specificity. This paper presents two case reports of multiple alveolar lymphangiomas found in black infants in a children\\'s hospital in Ireland. The epidemiology, aetiology, clinical presentation, histology, and management options are discussed. The photographs should aid the practitioner in recognising these lesions.

  19. Alveolar proteinosis in Behçet's disease

    OpenAIRE

    Tetikkurt Cuneyt; Tetikkurt Seza; Ozdemir Imran; Zuhur Cigdem; Bayar Nihal

    2010-01-01

    Abstract A 51-year-old man with Behçet's disease complained of fever, dry cough and dyspnea during exertion. Chest CT showed ground glass opacities with interstitial septal thickening in both lungs. Bronchoalveolar lavage (BAL) revealed amorphous and lipoproteinaceous material that was periodic acid-Schiff (PAS) stain positive. Transbronchial biopsy specimen demonstrated PAS positive alveolar eosinophilic material consistent with pulmonary alveolar proteinosis. Serum anti-granulocyte-macropha...

  20. Anaesthetic management of bilateral alveolar proteinosis for bronchopulmonary lavage.

    Directory of Open Access Journals (Sweden)

    Dixit R

    1998-01-01

    Full Text Available The most hazardous manifestation of pulmonary alveolar proteinosis is progressive hypoxia for which bronchopulmonary lavage (BPL is the single most effective treatment. Unfortunately this procedure under general anesthesia itself increases the risk of hypoxia due to the need for one lung ventilation. It was therefore considered interesting to report the successful anaesthetic management of a patient with pulmonary alveolar proteinosis for Bronchopulmonary lavage.