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Sample records for baboon alveolar macrophages

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

    Lifescience Database Archive (English)

    Full Text Available 18226603 Silica ... binding and toxicity in alveolar macrophages. Hamilton RF Jr, Thakur SA, Holian ... ub 2007 Dec 27. (.png) (.svg) (.html) (.csml) Show Silica ... binding and toxicity in alveolar macrophages. Pubm ... edID 18226603 Title Silica ... binding and toxicity in alveolar macrophages. Auth ...

  8. Effect of growth hormone on human alveolar macrophage oxidative metabolism

    OpenAIRE

    Keane, M. P.; Coakley, R.; COSTELLO, R; O'Neill, S. J.

    1997-01-01

    BACKGROUND: Growth hormone (GH) has diverse immunological actions and has been shown to augment oxidative metabolism in rat peritoneal and porcine alveolar macrophages and both human and animal neutrophils. A study was performed to determine the effects of GH on human alveolar macrophages in vitro. METHODS: Macrophages were harvested from 10 patients undergoing bronchoalveolar lavage and incubated with 0, 10 and 100 nmol/ml GH for four hours. Oxidative metabolism was assessed by means o...

  9. Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages.

    Science.gov (United States)

    Chen, S; Kammerl, I E; Vosyka, O; Baumann, T; Yu, Y; Wu, Y; Irmler, M; Overkleeft, H S; Beckers, J; Eickelberg, O; Meiners, S; Stoeger, T

    2016-06-01

    The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators. Immunoproteasomes are specialized types of proteasomes involved in shaping adaptive immune responses, but their role in innate immune signaling is still elusive. Here, we analyzed immunoproteasome function for polarization of alveolar macrophages, highly specialized tissue macrophages of the alveolar lung surface. Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNγ transcriptionally induced all three immunoproteasome subunits, low molecular mass protein 2 (LMP2), LMP7 and multicatalytic endopeptidase complex-like 1, which was accompanied by increased immunoproteasome activity in M1 cells. Deficiency of LMP7 had no effect on the LPS/IFNγ-triggered M1 profile indicating that immunoproteasome function is dispensable for classical alveolar macrophage activation. In contrast, IL-4 triggered alternative (M2) activation of primary alveolar macrophages was accompanied by a transcriptionally independent amplified expression of LMP2 and LMP7 and an increase in immunoproteasome activity. Alveolar macrophages from LMP7 knockout mice disclosed a distorted M2 profile upon IL-4 stimulation as characterized by increased M2 marker gene expression and CCL17 cytokine release. Comparative transcriptome analysis revealed enrichment of IL-4-responsive genes and of genes involved in cellular response to defense, wounding and inflammation in LMP7-deficient alveolar macrophages indicating a distinct M2 inflammation resolving phenotype. Moreover, augmented M2 polarization was accompanied by amplified AKT/STAT6 activation and increased RNA and protein expression of the M2 master transcription factor interferon regulatory factor 4 in LMP7(-/-) alveolar macrophages. IL-13 stimulation of LMP7-deficient macrophages induced a similar M2-skewed profile indicative for augmented signaling via the IL-4 receptor α (IL4Rα). IL4Rα expression was generally

  10. 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...

  11. 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...

  12. 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

  13. 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

  14. 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

  15. 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...

  16. 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...

  17. 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

  18. 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...

  19. 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

  20. 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

  1. In vitro studies of actinides and alveolar macrophages

    International Nuclear Information System (INIS)

    The toxicity of 239PuO2, 239Pu(NO3)4, and 241AmO2 to rabbit alveolar macrophages in culture was assessed. Comparison of toxicity of 239Pu(NO3)4 and 241AmO2 at the same radiation dose level indicates toxicity is due to radiation and not the chemical form of the actinide. Investigations were begun to determine the effect of serum macrophages and DTPA on 241AmO2 solubility

  2. 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...

  3. 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...

  4. 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.

  5. 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...

  6. 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.

  7. 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

  8. 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

  9. 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, …)

  10. 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...

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

    International Nuclear Information System (INIS)

    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.

  12. 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

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. Alveolar macrophage cytokine response to air pollution particles: Oxidant mechanisms

    International Nuclear Information System (INIS)

    Alveolar macrophages (AMs) primed with LPS and treated with concentrated ambient air particles (CAPs) showed enhanced release of tumor necrosis factor (TNF) and provide an in vitro model for the amplified effects of air pollution particles seen in people with preexisting lung disease. To investigate the mechanism(s) by which CAPs mediate TNF release in primed rat AMs, we first tested the effect of a panel of antioxidants. N-Acetyl-L-cysteine (20 mM), dimethyl thiourea (20 mM) and catalase (5 μM) significantly inhibited TNF release by primed AMs incubated with CAPs. Conversely, when LPS-primed AMs were treated with CAPs in the presence of exogenous oxidants (H2O2 generated by glucose oxidase, 10 μM/h), TNF release and cell toxicity was significantly increased. The soluble fraction of CAPs suspensions caused most of the increased bioactivity in the presence of exogenous H2O2. The metal chelator deferoxamine (DFO) strongly inhibited the interaction of the soluble fraction with H2O2 but had no effect on the bioactivity of the insoluble CAPs fraction. We conclude that CAPs can mediate their effects in primed AMs by acting on oxidant-sensitive cytokine release in at least two distinct ways. In the primed cell, insoluble components of PM mediate enhanced TNF production that is H2O2-dependent (catalase-sensitive) yet independent of iron (DFO-insensitive). In the presence of exogenous H2O2 released by AMs, PMNs, or other lung cells within an inflamed alveolar milieu, soluble iron released from air particles can also mediate cytokine release and cell toxicity

  18. 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

  19. 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.

  20. 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.

  1. 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...

  2. Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis

    Energy Technology Data Exchange (ETDEWEB)

    Rom, W.N.; Harkin, T. (New York Univ. Medical Center, New York (United States))

    1991-08-01

    Asbestosis is characterized by an alveolar macrophage alveolitis with injury and fibrosis of the lower respiratory tract. Alveolar macrophages recovered by bronchoalveolar lavage spontaneously release exaggerated amounts of oxidants including superoxide anion and hydrogen peroxide that may mediate alveolar epithelial cell injury. Dehydroepiandrosterone (DHEA) is a normally occurring adrenal androgen that inhibits glucose-6-phosphate dehydrogenase, the initial enzyme in the pentose phosphate shunt necessary for NADPH generation and superoxide anion formation. In this regard, the authors hypothesized that DHEA may reduce asbestos-induced oxidant release. DHEA added in vitro to alveolar macrophages lavaged from 11 nonsmoking asbestos workers significantly reduced superoxide anion release. DHEA is an antioxidant and potential anticarcinogenic agent that may have a therapeutic role in reducing the increased oxidant burden in asbestos-induced alveolitis of the lower respiratory tract.

  3. 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

  4. 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...

  5. 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.

  6. 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

  7. Temperature effect on endocytosis and exocytosis by rabbit alveolar macrophages

    International Nuclear Information System (INIS)

    Endocytosis of 125I-mannose-bovine serum albumin (BSA) and exocytosis of 125I-mannose-poly-D-lysine by rabbit alveolar macrophages were examined as a function of temperature. A plot for total ligand uptake (cell-associated ligand plus degraded ligand) versus time shows a single inflection point at 20 degrees C. Ligand degradation does not occur below 20 degrees C. Internalization of surface-bound 125I-mannose-BSA is negligible below 10 degrees C. The rate constant for internalization increases dramatically above 20 degrees C: 0.02 min-1 at 20 degrees C, 0.05 min-1 at 25 degrees C, 0.13 min-1 at 30 degrees C, and 0.29 min-1 at 35 degrees C. 125I-Mannose-N-acetyl-poly-D-lysine preloaded in lysosomes is exocytosed in a temperature and time-dependent fashion. Even at lower temperatures (2-10 degrees C), secretion of 125I-mannose-N-acetyl-poly-D-lysine was detected, indicating that movement of lysosomal content to plasma membrane and beyond cannot be suppressed at these temperatures. Thus, the temperature dependence of exocytosis of an 125I-labeled ligand is quite different from that of endocytosis, suggesting that the two processes are controlled by different mechanisms. Stimulation of secretion of preloaded 125I-mannose-N-acetyl-poly-D-lysine by mannose-BSA was more pronounced at lower temperatures with a sharp inflection point at 10 degrees C. These findings suggest that endosomes containing newly internalized mannose-BSA interact with the exocytosis pathway and enhance secretion of 125I-mannose-N-acetyl-poly-D-lysine from lysosomes

  8. Influence of Rhodococcus equi on the respiratory burst of resident alveolar macrophages from horses

    International Nuclear Information System (INIS)

    Rhodococcus equi is the etiologic agent of a devastating pneumonia of sporadic incidence in foals. The purpose of this study was to evaluate the influence of R. equi on the superoxide anion production, measured spectrophotometrically as the reduction of cytochrome C, and hexose monophosphate shunt activity, measured by 14CO2 liberation from 14C-1-D-glucose, of alveolar macrophages from horses. Alveolar macrophages were harvested from 6 anesthetized, healthy, light-breed, adult horses by bronchoalveolar lavage. Following a randomized complete block design, the suspension of cells was divided into aliquots of 106 viable alveolar macrophages which were exposed to 1, 10 or 100 g. of opsonized R. equi or opsonized zymosan A at 37 C for 2 hours. In this study the respiratory burst of equine alveolar macrophages was only evidenced by the hexose monophosphate shunt activity and superoxide anion was not coincidentally produced. Rhodococcus equi did not adversely affect that response. The insignificant superoxide anion production by the alveolar macrophages suggests that this may not be a significant oxygen metabolite in those cells

  9. 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...

  10. 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

    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 tiss...

  11. 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.

  12. 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

  13. 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

  14. 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...

  15. The carbohydrates associated with the surfaces of hamster alveolar macrophages: a study using fluorescein-conjugated lectins.

    OpenAIRE

    Meban, C.

    1985-01-01

    Alveolar macrophages were isolated from the lungs of hamsters by lavage and centrifugation. The harvesting procedure yielded about 5.2 X 10(6) cells per animal and the majority of these cells were viable as assessed by a Trypan blue exclusion test. Monolayers of macrophages were labelled with a series of FITC-conjugated lectins. The results of this study suggest that the surface coating of the alveolar macrophages contains the following carbohydrate groups: N-acetylgalactosamine, N-acetylgluc...

  16. 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

  17. 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...

  18. EFFECTS OF OZONE EXPOSURE ON LIPID METABOLISM IN HUMAN ALVEOLAR MACROPHAGES

    Science.gov (United States)

    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. ollowing release, there can be subsequent metabolism of AA into various potent, biological active m...

  19. 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.

  20. 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

  1. 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

  2. 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

  3. [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

  4. 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...... analysis of cell size and membrane integrity) led to 40% reduction in the total number of phagocytozing cells. However, viable/uninfected macrophages in PRRSV-infected cultures exhibited normal phagocytic ability at 48 h, indicating that no soluble phagocytosis-suppressive mediators were induced by PRRSV...... infection in this system. In short, in our minimal system containing only a single cell type, phagocytosis-suppressive effects of PRRSV infection were detected, that acted at the culture level by reducing the total number of alveolar lung macrophages....

  5. 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

  6. 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

  7. 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

  8. 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)

  9. 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)

  10. Evaluation of the alveolar macrophage role in the pulmonary distribution of actinide oxides

    International Nuclear Information System (INIS)

    Actinide oxide inhalation is potentially a risk during the fuel fabrication process in the electronuclear industry. These particles can induce pulmonary lesions. The alveolar macrophage play an important role in the particle sequestration and transport but the actinide toxicity towards these cells is not well known. The aim of this work was to characterize the evolution of particle localisation in lungs after inhalation and to evaluate the role of macrophages in the lesion histo-genesis. We have used of a solid track detector to visualise alpha dose distribution within lung tissue. After 237NpO2, MOX or PuO2 inhalation by rats, different kinetics of clearance were observed for the sub-pleural and peri-bronchial areas compared to the others alveolar areas. For initial lung burdens that alter the lung clearance, particle aggregates were observed. Their kinetic and localisation vary depending on the aerosol, for a same global dose delivered to the lungs. This could be due to the different specific alpha activities of the particles and to the particle number deposited in the lung to obtain a similar burden but it could be also due to a chemical toxicity of neptunium higher than that of the others actinides. The flow cytometry methods developed allow us to measure apoptosis, phagocytosis and free radicals generation. After addition of soluble uranium to the culture medium, similar results were obtained using either alveolar macrophages extracted from rats or a macrophage cell line. This work confirms that alveolar macrophages are involved in the aggregate formation which induces heterogeneous dose distribution within the different lung tissues. (author)

  11. 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

  12. 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...

  13. 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 ...

  14. 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...

  15. 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

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

    OpenAIRE

    Friedman, M.; Madden, M C; Samet, J M; Koren, H S

    1992-01-01

    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. After release, there can be subsequent metabolism of AA into various potent, biologically 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 after ozone (O3) exposu...

  17. 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...

  18. Autophagic Killing Effects against Mycobacterium tuberculosis by Alveolar Macrophages from Young and Aged Rhesus Macaques

    OpenAIRE

    Pacheco, Sophia A.; Powers, Katelyn M.; Engelmann, Flora; Messaoudi, Ilhem; Purdy, Georgiana E.

    2013-01-01

    Non-human primates, notably rhesus macaques (Macaca mulatta, RM), provide a robust experimental model to investigate the immune response to and effective control of Mycobacterium tuberculosis infections. Changes in the function of immune cells and immunosenescence may contribute to the increased susceptibility of the elderly to tuberculosis. The goal of this study was to examine the impact of age on M. tuberculosis host-pathogen interactions following infection of primary alveolar macrophages...

  19. Up-regulation of alveolar macrophage matrix metalloproteinases in HIV1+ smokers with early emphysema

    OpenAIRE

    Kaner, Robert J.; Santiago, Francisco; Crystal, Ronald G.

    2009-01-01

    HIV1+ smokers develop emphysema at an earlier age and with a higher incidence than HIV1– smokers. Since human alveolar macrophages (AMs) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that up-regulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1+ smokers. Microarray analysis was used to screen which matrix metalloproteinases (MMPs) genes were expressed by AM of HIV1+ smokers with early emphysema. For each of t...

  20. Transcription analysis of the porcine alveolar macrophage response to porcine circovirus type 2

    OpenAIRE

    Li, Wentao; Liu, Shuqing; Wang, Yang; Deng, Feng; Yan, Weidong; YANG Kun; Chen, Huanchun; He, Qigai; Charreyre, Catherine; Audoneet, Jean-Christophe

    2013-01-01

    Background Porcine circovirus type 2 (PCV2) is the causal agent of postweaning multisystemic wasting syndrome (PMWS), which has severely impacted the swine industry worldwide. PCV2 triggers a weak and atypical innate immune response, but the key genes and mechanisms by which the virus interferes with host innate immunity have not yet been elucidated. In this study, genes that control the response of primary porcine alveolar macrophages (PAMs), the main target of PCV2, were profiled in vitro. ...

  1. 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...

  2. 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...

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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...

  9. 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, ...

  10. 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

  11. STAT6 expression in T cells, alveolar macrophages and bronchial biopsies of normal and asthmatic subjects

    Directory of Open Access Journals (Sweden)

    Tomita Katsuyuki

    2012-03-01

    Full Text Available Abstract Background Asthma is characterised by increased numbers of Th2-like cells in the airways and IgE secretion. Generation of Th2 cells requires interleukin (IL-4 and IL-13 acting through their specific receptors and activating the transcription factor, signal transducer and activator of transcription 6 (STAT6. STAT6 knockout mice fail to produce IgE, airway hyperresponsiveness and bronchoalveolar lavage eosinophilia after allergen sensitisation, suggesting a critical role for STAT6 in allergic responses. Methods We have investigated the expression of STAT6 in peripheral blood T-lymphocytes, alveolar macrophages and bronchial biopsies from 17 normal subjects and 18 mild-moderate steroid-naïve stable asthmatic patients. Results STAT6 expression was variable and was detected in T-lymphocytes, macrophages and bronchial epithelial cells from all subjects with no difference between normal and stable asthmatic subjects. Conclusions STAT6 expression in different cells suggests that it may be important in regulating the expression of not only Th2-like cytokines in T cells of man, but may also regulate STAT-inducible genes in alveolar macrophages and airway epithelial cells.

  12. 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

  13. Repopulation of murine alveolar macrophage colony-forming cells after whole body irradiation

    International Nuclear Information System (INIS)

    A study was made of the repopulation of alveolar macrophage colony-forming cells (AL-CFC) after a supra lethal irradiation and bone marrow transplantation in mice. The repopulation of both CFU-S (hemopoietic stem cells) and the committed stem cells for both granulocytes and monocytes (GM-CFC) in the femoral bone marrow occurred within 2 weeks. In sharp contrast, the repopulation of AL-CFC in the lung was a very slow process. The number of AL-CFC, which are more resistant to irradiation than both CFU-S and GM-CFC, was reduced to 1% of control values one day after the irradiation and recovered slowly with time. It took almost nine weeks for the number of AL-CFC per mouse to reach normal levels. The number of recoverable alveolar cells in these mice never dropped below 70% of control values and reached the nadir about two weeks after the irradiation. (UK)

  14. 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

  15. In vitro cytotoxicity of Manville Code 100 glass fibers: Effect of fiber length on human alveolar macrophages

    Directory of Open Access Journals (Sweden)

    Jones William

    2006-03-01

    Full Text Available Abstract Background Synthetic vitreous fibers (SVFs are inorganic noncrystalline materials widely used in residential and industrial settings for insulation, filtration, and reinforcement purposes. SVFs conventionally include three major categories: fibrous glass, rock/slag/stone (mineral wool, and ceramic fibers. Previous in vitro studies from our laboratory demonstrated length-dependent cytotoxic effects of glass fibers on rat alveolar macrophages which were possibly associated with incomplete phagocytosis of fibers ≥ 17 μm in length. The purpose of this study was to examine the influence of fiber length on primary human alveolar macrophages, which are larger in diameter than rat macrophages, using length-classified Manville Code 100 glass fibers (8, 10, 16, and 20 μm. It was hypothesized that complete engulfment of fibers by human alveolar macrophages could decrease fiber cytotoxicity; i.e. shorter fibers that can be completely engulfed might not be as cytotoxic as longer fibers. Human alveolar macrophages, obtained by segmental bronchoalveolar lavage of healthy, non-smoking volunteers, were treated with three different concentrations (determined by fiber number of the sized fibers in vitro. Cytotoxicity was assessed by monitoring cytosolic lactate dehydrogenase release and loss of function as indicated by a decrease in zymosan-stimulated chemiluminescence. Results Microscopic analysis indicated that human alveolar macrophages completely engulfed glass fibers of the 20 μm length. All fiber length fractions tested exhibited equal cytotoxicity on a per fiber basis, i.e. increasing lactate dehydrogenase and decreasing chemiluminescence in the same concentration-dependent fashion. Conclusion The data suggest that due to the larger diameter of human alveolar macrophages, compared to rat alveolar macrophages, complete phagocytosis of longer fibers can occur with the human cells. Neither incomplete phagocytosis nor length-dependent toxicity was

  16. Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation

    OpenAIRE

    Pengxiang Chang; Kuchipudi, Suresh V; Kenneth H. Mellits; Sujith Sebastian; Joe James; Jinhua Liu; Holly Shelton; Kin-Chow Chang

    2015-01-01

    Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of PAM in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (H2N3 and H6N1) and three mammalian (swine H1N1, human H1N1 and pandemic H1N1) in...

  17. 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...

  18. 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)

  19. Certain biochemical specificities of alveolar macrophages from gamma-irradiated guinea pigs

    International Nuclear Information System (INIS)

    The changes in the metabolism of alveolar macrophages (aMas) from 0.5 Gy and 2 Gy gamma-irradiated guinea pigs have been studied. In view of predominantly aerobic metabolism of the aMas the investigations include oxygen uptake in the presence of substrate glucose as well as the activity of cytochrome oxidase and acid phosphatase. The results show that in the macrophages obtained from 2 Gy exposed guinea pigs there is simultaneous intensification of the oxygen uptake in the presence of glucose and of cytochrome oxidase activity by the 3rd day after irradiation. In the macrophages from the 0.5 Gy exposed guinea pigs there is also parallelism in the intensification of the respiration and cytochrome oxidase activity but on the 7th day of the investigation. In both doses applied the activity of the acid phosphatase of macrophages sharply increases to reach the maximum values between the 3rd and 7th days after irradiation. This discrepancy between the intracellular bactericidal effect and the respiration activity and the acid phosphatase of the aMas give grounds to support the view of Pavillard and Rowlei that the total metabolism of the aMas is not a limiting factor in relation to their intracellular killing effect on the absorbed bacteria. 3 figs., 6 refs

  20. Functional ability and fate of pulmonary alveolar macrophages after intratracheal instillation into rats

    International Nuclear Information System (INIS)

    Pulmonary alveolar macrophages (PAM) from donor rats were intratracheally instilled into recipient rats to determine if donor macrophages were functionally similar to the recipient's own macrophages. Recipient and donor (extrinsic) PAM were equivalent in their ability to phagocytize 1.7 μm and 3.9 μm latex microspheres in vivo and sensitized sheep red blood cells in vitro. Also, the extrinsic PAM appeared functionally equivalent to recipient PAM with respect to ability to translocate into interstitial tissue and migrate to the lung-associated lymph nodes (LALN). The recipient PAN appeared to phagocytize the extrinsic PAM, but the extrinsic PAM did not appear to phagocytize the recipient PAM. This could represent a different degree of physiological coordination of intrinsic and extrinsic PAM activities in the lung. Overall, results indicated that extrinsic PAM can live and function in the lungs of recipient rats, and perform most or all of the functions ascribed to recipient PAM. Results also support the hypothesis that PAM are able to move into the pulmonary interstitium and translocate to the LALM without the involvement of other pulmonary macrophages. (author)

  1. 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

  2. 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

  3. 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

  4. 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

  5. Phagocytosis of viable Candida albicans by alveolar macrophages: flow cytometric quantification.

    Science.gov (United States)

    Rosseau, S; Seeger, W; Pralle, H; Lohmeyer, J

    1994-08-01

    The phagocytic capacity of blood leukocytes may be assessed by flow cytometric techniques using fluorochrome-labeled particles including viable microorganisms. Application of this approach to alveolar macrophages (AM) is hampered or even rendered impossible by the strong autofluorescence of this cell type, superimposing the fluorescence intensity of the labeled phagocytic targets. Viable Candida albicans were loaded with the membrane-permeable fluorescent dye carboxy-seminaphtorhodafluor 2/acetoxymethylester (carboxy-SNARF 2-AM), which is cleaved intracellularly to generate the membrane-impermeable derivative carboxy-SNARF 2. Fluorescence was excited with the 488-nm line of an argon-ion laser, and the emission peak at 633 nm was used for quantification of dye-associated fluorescence. Rabbit and human AM were labeled with fluorescein isothiocyanate-coupled monoclonal mouse anti-macrophage antibodies. After coincubation of macrophages and yeast, 4% paraformaldehyde plus 0.5% EDTA in phosphate-buffered saline was used to stop the phagocytic process and detach adherent yeast from the AM surface. Macrophages loaded with yeast displayed a shift from monochromatic (green) to dual (green and red) fluorescence. The percentage of yeast-positive AM and red fluorescence intensity of phagocytosing macrophages were quantified. Yeast opsonization with serum or anti-Candida immunoglobulins was a prerequisite for phagocytosis. Under optimized conditions (0.5-10% serum; 60 min yeast-AM incubation; yeast-AM ratio 8:1 to 12:1), 71-91% of the AM were involved in the phagocytic process. Yeast engulfment was completely inhibited by N-ethylmaleimide and iodoacetic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8074245

  6. Co-spray dried resveratrol and budesonide inhalation formulation for reducing inflammation and oxidative stress in rat alveolar macrophages.

    Science.gov (United States)

    Trotta, Valentina; Lee, Wing-Hin; Loo, Ching-Yee; Young, Paul M; Traini, Daniela; Scalia, Santo

    2016-04-30

    Oxidative stress is instrumental in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Novel therapeutic strategies that target macrophages, based on the use of antioxidant compounds, could be explored to improve corticosteroid responses in COPD patients. In this study, inhalable microparticles containing budesonide (BD) and resveratrol (RES) were prepared and characterized. This approach was undertaken to develop a multi-drug inhalable formulation with anti-oxidant and anti-inflammatory activities for treatment of chronic lung diseases. The inhalable microparticles containing different ratios of BD and RES were prepared by spray drying. The physico-chemical properties of the formulations were characterized in terms of surface morphology, particle size, physical and thermal stability. Additionally, in vitro aerosol performances of these formulations were evaluated with the multi-stage liquid impinger (MSLI) at 60 and 90l/min, respectively. The cytotoxicity effect of the formulations was evaluated using rat alveolar macrophages. The biological responses of alveolar macrophages in terms of cytokine expressions, nitric oxide (NO) production and free radical scavenging activities were also tested. The co-spray dried (Co-SD) microparticles of all formulations exhibited morphologies appropriate for inhalation administration. Analysis of the deposition profiles showed an increase in aerosol performance proportional to BD concentration. Cell viability assay demonstrated that alveolar macrophages could tolerate a wide range of RES and BD concentrations. In addition, RES and BD were able to decrease the levels of tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS) induced alveolar macrophages. This study has successfully established the manufacture of Co-SD formulations of RES and BD with morphology and aerosol properties suitable for inhalation drug delivery, negligible in vitro toxicity and enhanced

  7. 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

  8. 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

  9. Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions.

    Science.gov (United States)

    Bordbar, Aarash; Lewis, Nathan E; Schellenberger, Jan; Palsson, Bernhard Ø; Jamshidi, Neema

    2010-10-19

    Metabolic coupling of Mycobacterium tuberculosis to its host is foundational to its pathogenesis. Computational genome-scale metabolic models have shown utility in integrating -omic as well as physiologic data for systemic, mechanistic analysis of metabolism. To date, integrative analysis of host-pathogen interactions using in silico mass-balanced, genome-scale models has not been performed. We, therefore, constructed a cell-specific alveolar macrophage model, iAB-AMØ-1410, from the global human metabolic reconstruction, Recon 1. The model successfully predicted experimentally verified ATP and nitric oxide production rates in macrophages. This model was then integrated with an M. tuberculosis H37Rv model, iNJ661, to build an integrated host-pathogen genome-scale reconstruction, iAB-AMØ-1410-Mt-661. The integrated host-pathogen network enables simulation of the metabolic changes during infection. The resulting reaction activity and gene essentiality targets of the integrated model represent an altered infectious state. High-throughput data from infected macrophages were mapped onto the host-pathogen network and were able to describe three distinct pathological states. Integrated host-pathogen reconstructions thus form a foundation upon which understanding the biology and pathophysiology of infections can be developed. PMID:20959820

  10. 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

  11. Kinetics of uptake and distribution of arachidonic acid by rat alveolar macrophages

    International Nuclear Information System (INIS)

    The time course of uptake and distribution of 3H-arachidonic acid (3H-AA) into rat alveolar macrophage phospholipid pools was examined. Macrophages incubated with exogenous 3H-AA in RPMI-1640 containing 0.1% bovine serum albumin (BSA), incorporated this radiolabel into phosphatidylcholine and phosphatidylinositol (PI) with plateaus reached within 2 to 4 hours, which remained relatively constant for up to 18 hours. Incorporation of 3H-AA into phosphatidylethanolamine was small, but continued to increase for 14 hours. Analysis of phosphate content in phospholipid pools revealed that treatment with exogenous 5 nM arachidonic acid had no effect upon pool sizes, but there was a selective incorporation of 3H-AA into PI. Cells were incubated with 3H-AA in RPMI alone or medium containing either 0.2% lactalbumin, fetal calf serum at variable concentrations, 10% Nu Serum, or 0.1% BSA. Incubation of macrophages with 3H-AA in RPMI alone or containing 0.2% lactalbumin, resulted in approximately 70% of the radiolabel taken up by the cells being incorporated into triglyceride. The addition of BSA to RPMI-1640 medium was found to facilitate selective uptake of 3H-AA into phospholipids. Approximately 70% of incorporated 3H-AA was releasable through the action of exogenous phospholipase A2

  12. Increased levels of inflammatory cytokines and endothelin-1 in alveolar macrophages from patients with chronic heart failure.

    Directory of Open Access Journals (Sweden)

    Liv I Bjoner Sikkeland

    Full Text Available BACKGROUND: Pathophysiological interactions between heart and lungs in heart failure (HF are well recognized. We investigated whether expression of different factors known to be increased in the myocardium and/or the circulation in HF is also increased in alveolar macrophages in HF. METHODOLOGY/PRINCIPAL FINDINGS: Lung function, hemodynamic parameters, gene expression in alveolar macrophages, and plasma levels in the pulmonary and femoral arteries of HF patients (n = 20 were compared to control subjects (n = 16. Our principal findings were: (1 Lung function was significantly lower in HF patients compared to controls (P<0.05. (2 mRNA levels of ET-1, tumor necrosis factor (TNF-α and interleukin-6 (IL-6 were increased in alveolar macrophages from HF patients. (3 Plasma levels of ET-1, TNFα, IL-6 and MCP-1 were significantly increased in HF patients, whereas our data indicate a net pulmonary release of MCP-1 into the circulation in HF. CONCLUSIONS/SIGNIFICANCE: Several important cytokines and ET-1 are induced in alveolar macrophages in human HF. Further studies should clarify whether increased synthesis of these factors affects pulmonary remodeling and, directly or indirectly, adversely affects the failing myocardium.

  13. 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.

  14. 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.

  15. Effect of 89Sr-induced monocytopenia on splenic and pulmonary alveolar macrophage populations in a normal steady state

    International Nuclear Information System (INIS)

    A bone-seeking radioisotope, 89Sr eliminates blood monocytes and their precursors in the bone marrow after a selective deposition in the skeletal bone. In the present study, we investigated whether or not such a prominent monocyte depletion can induce any alterations in tissue macrophage populations in 89Sr-injected mice. The number of monocytes or leukocytes possessing a macrophage differentiation antigen, Mac-1, phagocytic or Fc receptor (FcR) activity was significantly reduced in the blood and the bone marrow for about 6 weeks after 89Sr administration. Splenic macrophages characterized by these phenotypic or functional markers were not, however, altered in number during the post-injection period, despite the fact that the total number of spleen cells recovered significantly increased together with macrophage colony forming stem cells (M-CFC) and cells under DNA synthesis. The population of lavaged pulmonary alveolar macrophages (PAM) was invariable not only in the number recovered but also in DNA synthesis. Colony formation by PAM was consistently noted, and the total number of M-CFC in the lung was not reduced during the 8 weeks post-injection period. These results indicate that 89Sr-induced depletion of bone marrow-derived monocytes/macrophages or their precursors has little effect at least on the number of splenic and pulmonary alveolar macrophage populations in a normal steady state. (author)

  16. 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

  17. 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

  18. Comparative morphology and morphometry of alveolar macrophages from six mammalian species

    International Nuclear Information System (INIS)

    Pulmonary alveolar macrophages (PAM) were collected from normal, healthy mice, rats, dogs, cynomolgus monkeys, chimpanzees and humans and evaluated for morphologic and morphometric characteristics. The PAM of mice, rats, and dogs were morphologically similar to one another and had statistically similar frequency distributions for PAM size. The range of cell size for these three species was narrow. The PAM of nonhuman primates and humans were morphologically heterogenous with increased cytoplasmic vacuolation, irregular cell outlines and increased numbers of multi nucleated cells as compared to the PAM of rodents and dogs. The mean size of human PAMs was statistically greater than that for all other species evaluated, including nonhuman primates. These data indicate that significant differences in PAM morphology and size exist among species and that such differences may be important when selecting species for studies of PAM. (author)

  19. 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.)

  20. Alveolar macrophages modulate the epithelial cell response to coal dust in vitro.

    Science.gov (United States)

    Lee, Y C; Rannels, D E

    1996-01-01

    The response of the alveolar epithelium to coal dust exposure is poorly understood. Coal or other dusts may act on the epithelium directly or indirectly through nearby alveolar macrophages (AM) that produce cytokines and other soluble products. AM and type II pneumocytes (T2P) were thus exposed to dust in coculture to evaluate their possible interactions. Anthracite coal dust PSOC 867 increased synthesis of extracellular matrix (ECM) components by T2P. AM alone did not produce ECM. Similarly, coculture of T2P with AM (3.75:1) had little effect on epithelial ECM synthesis. In contrast, coculture of T2P with AM significantly increased PSOC 867 effects on T2P rates of ECM synthesis, ECM fibronectin content, and T2P levels of fibronectin mRNA. AM-conditioned medium did not change the PSOC 867 effect on T2P. Neither control nor PSOC 867-treated AM on Falcon culture inserts (0.45-micron pore size) over T2P stimulated ECM synthesis by either untreated or dust-exposed epithelium. Thus AM-mediated changes in ECM synthesis by PSOC 867-treated T2P require close cell-cell interactions, suggesting a role for cell-cell contact or for short-lived soluble mediators of the AM effects. PMID:8772535

  1. Alveolar macrophages are the main target cells in feline calicivirus-associated pneumonia.

    Science.gov (United States)

    Monné Rodriguez, J M; Soare, T; Malbon, A; Blundell, R; Papoula-Pereira, R; Leeming, G; Köhler, K; Kipar, A

    2014-08-01

    Feline calicivirus (FCV) is a pathogen of felids and one of the most common causative agents of feline upper respiratory disease (URD). Reports of natural FCV pneumonia in the course of respiratory tract infections are sparse. Therefore, knowledge on the pathogenesis of FCV-induced lung lesions comes only from experimental studies. The aim of the present study was to assess the type and extent of pulmonary involvement in natural respiratory FCV infections of domestic cats and to identify the viral target cells in the lung. For this purpose, histology, immunohistochemistry and RNA-in situ hybridisation for FCV and relevant cell markers were performed on diagnostic post-mortem specimens collected after fatal URD, virulent systemic FCV or other conditions. All groups of cats exhibited similar acute pathological changes, dominated by multifocal desquamation of activated alveolar macrophages (AM) and occasional type II pneumocytes with fibrin exudation, consistent with diffuse alveolar damage (DAD). In fatal cases, this was generally seen without evidence of epithelial regeneration. In cats without clinical respiratory signs, type II pneumocyte hyperplasia was present alongside the other changes, consistent with the post-damage proliferative phase of DAD. FCV infected and replicated in AM and, to a lesser extent, type II pneumocytes. This study shows that lung involvement is an infrequent but important feature of FCV-induced URD. AM are the main viral target cell and pulmonary replication site, and their infection is associated with desquamation and activation, as well as death via apoptosis. PMID:24857252

  2. 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

  3. 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.

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

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    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.

  5. 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

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. 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

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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 ...

  15. Importance of Bacterial Replication and Alveolar Macrophage-Independent Clearance Mechanisms during Early Lung Infection with Streptococcus pneumoniae

    OpenAIRE

    Camberlein, Emilie; Cohen, Jonathan M.; José, Ricardo; Hyams, Catherine J.; Callard, Robin; Chimalapati, Suneeta; Yuste, Jose; Edwards, Lindsey A.; Marshall, Helina; van Rooijen, Nico; Noursadeghi, Mahdad; Brown, Jeremy S.

    2015-01-01

    Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveol...

  16. In vitro cytotoxicity of Manville Code 100 glass fibers: Effect of fiber length on human alveolar macrophages

    OpenAIRE

    Jones William; Baron Paul; Deye Gregory J; Clark Melissa P; Ameredes Bill T; Calhoun William J; Zeidler-Erdely Patti C; Blake Terri; Castranova Vincent

    2006-01-01

    Abstract Background Synthetic vitreous fibers (SVFs) are inorganic noncrystalline materials widely used in residential and industrial settings for insulation, filtration, and reinforcement purposes. SVFs conventionally include three major categories: fibrous glass, rock/slag/stone (mineral) wool, and ceramic fibers. Previous in vitro studies from our laboratory demonstrated length-dependent cytotoxic effects of glass fibers on rat alveolar macrophages which were possibly associated with incom...

  17. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. The effects of beryllium metal particles on the viability and function of cultured rat alveolar macrophages

    International Nuclear Information System (INIS)

    Rat pulmonary alveolar macrophages (PAM) were exposed in vitro to beryllium metal particles. The particles used were relatively large (Be-II) and small (Be-V) size fractions of beryllium metal obtained from an aerosol cyclone, and a beryllium metal aerosol generated by laser vaporization of beryllium metal in an argon atmosphere (Be-L). Glass beads (GB) were used as a negative control particle. The endpoints examined included cell killing (trypan blue dye exclusion) and phagocytic ability (sheep red blood cell uptake). Phagocytic ability was inhibited by beryllium particles at concentrations that did not cause appreciable cell killing. Results based on the mass concentration of particles in culture medium were transformed by the amount of specific surface area of the particles to permit expression of toxicity on the basis of amount of surface area of particles per unit volume of culture medium. On a mass concentration basis, the order of cytotoxicity was Be-L > Be-V ∼ Be-II > GB; for inhibition of phagacytosis, the cytotoxicity order was Be-L ∼ Be-V > Be-II > GB. On a surface area concentration basis, the order of toxicity for viability was altered to Be-II > Be-L ∼ Be-V (with GB indeterminant) and to Be-V > Be-II ∼ Be-L > GB for inhibition of phagocytosis. We conclude that there are factors in addition to specific surface area that influence the expression of toxic effects in cultured PAM. (author)

  1. 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)

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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)

  5. 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...

  6. 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.

  7. Training modifies innate immune responses in blood monocytes and in pulmonary alveolar macrophages.

    Science.gov (United States)

    Frellstedt, Linda; Waldschmidt, Ingrid; Gosset, Philippe; Desmet, Christophe; Pirottin, Dimitri; Bureau, Fabrice; Farnir, Frédéric; Franck, Thierry; Dupuis-Tricaud, Marie-Capucine; Lekeux, Pierre; Art, Tatiana

    2014-07-01

    In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs) and costimulatory and antigen-presenting molecules. Lower airway diseases are also a common problem in sport and racing horses. Because innate immunity plays an essential role in lung defense mechanisms, we assessed the effect of acute exercise and training on innate immune responses in two different compartments. Blood monocytes and pulmonary alveolar macrophages (PAMs) were collected from horses in untrained, moderately trained, intensively trained, and deconditioned states before and after a strenuous exercise test. The cells were analyzed for TLR messenger ribonucleic acid (mRNA) expression by real-time PCR in vitro, and cytokine production after in vitro stimulation with TLR ligands was measured by ELISA. Our results showed that training, but not acute exercise, modified the innate immune responses in both compartments. The mRNA expression of TLR3 was down-regulated by training in both cell types, whereas the expression of TLR4 was up-regulated in monocytes. Monocytes treated with LPS and a synthetic diacylated lipoprotein showed increased cytokine secretion in trained and deconditioned subjects, indicating the activation of cells at the systemic level. The production of TNF-α and IFN-β in nonstimulated and stimulated PAMs was decreased in trained and deconditioned horses and might therefore explain the increased susceptibility to respiratory infections. Our study reports a dissociation between the systemic and the lung response to training that is probably implicated in the systemic inflammation and in the pulmonary susceptibility to infection. PMID:24502337

  8. 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.

  9. 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

  10. 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.

  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. 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

  14. 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)

  15. 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)

  16. 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...

  17. 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.

  18. 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...

  19. 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

  20. 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

  1. 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.

  2. Hyporeactivity of Alveolar Macrophages and Higher Respiratory Cell Permissivity Characterize DBA/2J Mice Infected by Influenza A Virus.

    Science.gov (United States)

    Casanova, Tomás; Van de Paar, Els; Desmecht, Daniel; Garigliany, Mutien-Marie

    2015-10-01

    Influenza A virus remains a major public health problem. Mouse models have been widely used to study influenza infection in mammals. DBA/2J and C57BL/6J represent extremes in terms of susceptibility to influenza A infection among inbred laboratory mouse strains. Several studies focused specifically on the factors responsible for the susceptibility of DBA/2J or the resistance of C57BL/6J and resulted in impressive lists of candidate genes or factors over- or underexpressed in one of the strains. We adopted a different phenotypical approach to identify the critical steps of the infection process accounting for the differences between DBA/2J and C57BL/6J strains. We concluded that both a dysfunction of alveolar macrophages and an increased permissivity of respiratory cells rendered DBA/2J more susceptible to influenza infection. PMID:26134384

  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. PMID:7505240

  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. 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

  8. 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.

  9. 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

  10. 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...

  11. Anti-inflammatory effects of myrtol standardized and other essential oils on alveolar macrophages from patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Rantzsch U

    2009-12-01

    Full Text Available Abstract Introduction Myrtol standardized is established in the treatment of acute and chronic bronchitis and sinusitis. It increases mucociliar clearance and has muco-secretolytic effects. Additional anti-inflammatory and antioxidative properties have been confirmed for Myrtol standardized, eucalyptus oil, and orange oil in several in vitro studies. Objective The aim of this study was to prove the ability of essential oils to reduce cytokines release and reactive oxygen species (ROS production derived from ex vivo cultured alveolar macrophages. Material and methods Alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD, n = 26, GOLD III-IV were pre-cultured with essential oils (10-3-10-8% for 1 h and then stimulated with LPS (1 μg/ml. After 4 h and 20 h respectively a cellular reactive oxygen species (ROS using 2',7'-dichlorofluorescein (DCF, and b TNF-α, IL-8, and GM-CSF secretion were quantified. Results In comparison with negative controls, pre-cultured Myrtol, eucalyptus oil and orange oil (10-4% reduced in the LPS-activated alveolar macrophages ROS release significantly after 1+20 h as follows: Myrtol - 17.7% (P = 0.05, eucalyptus oil -21.8% (P α reduction: Myrtol (-37.3%, P α reduction at 1+4 h and 1+20 h did not vary (Myrtol: -31.9% and -37.3% respectively, P = 0.372 indicating that this effect occurs early and cannot be further stimulated. Myrtol reduced the release of GMCSF by -35.7% and that of IL-8 only inconsiderably. Conclusions All essential oils tested have effective antioxidative properties in ex vivo cultured and LPS-stimulated alveolar macrophages. Additionally, Myrtol inhibited TNF-α and GM-CSF release best indicating additional potent anti-inflammator y activity.

  12. 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...

  13. 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.)

  14. Patent ductus arteriosus ligation alters pulmonary gene expression in preterm baboons

    OpenAIRE

    Waleh, Nahid; McCurnin, Donald C.; Yoder, Bradley A.; Shaul, Philip W.; Clyman, Ronald I.

    2011-01-01

    Ibuprofen-induced ductus closure improves pulmonary mechanics and increases alveolar surface area in premature baboons compared with baboons with a persistent patent ductus arteriosus (PDA). Ibuprofen-treatment has no effect on the expression of genes that regulate pulmonary inflammation but does increase the expression of alpha-ENaC (the transepithelial sodium channel that is critical for alveolar water clearance). Although ligation eliminates the PDA, it does not improve pulmonary mechanics...

  15. 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.

  16. Sonicated Protein Fractions of Mycoplasma hyopneumoniae Induce Inflammatory Responses and Differential Gene Expression in a Murine Alveolar Macrophage Cell Line.

    Science.gov (United States)

    Damte, Dereje; Lee, Seung-Jin; Birhanu, Biruk Tesfaye; Suh, Joo-Won; Park, Seung-Chun

    2015-12-28

    Mycoplasma hyopneumoniae is known to cause porcine enzootic pneumonia (EP), an important disease in swine production. The objective of this study was to examine the effects of sonicated protein fractions of M. hyopneumoniae on inflammatory response and gene expression in the murine alveolar macrophage MH-S cell line. The effects of sonicated protein fractions and intact M. hyopneumoniae on the gene expression of cytokines and iNOS were assessed using RT-PCR. The Annealing Control Primer (ACP)-based PCR method was used to screen differentially expressed genes. Increased transcription of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, COX-2, and iNOS mRNA was observed after exposure to the supernatant (SPT), precipitant (PPT), and intact M. hyopneumoniae protein. A time-dependent analysis of the mRNA expression revealed an upregulation after 4 h for IL-6 and iNOS and after 12 h for IL-1β and TNF-α, for both SPT and PPT; the fold change in COX-2 expression was less. A dose- and time-dependent correlation was observed in nitrite (NO) production for both protein fractions; however, there was no significant difference between the effects of the two protein fractions. In a differential gene analysis, PCR revealed differential expression for nine gene bands after 3 h of stimulation - only one gene was downregulated, while the remaining eight were upregulated. The results of this study provide insights that help improve our understanding of the mechanisms underlying the pathogenesis of and macrophage defenses against M. hyopneumoniae assault, and suggest targets for future studies on therapeutic interventions for M. hyopneumoniae infections. PMID:26370797

  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. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Nitrated Fatty Acids Reverse Cigarette Smoke-Induced Alveolar Macrophage Activation and Inhibit Protease Activity via Electrophilic S-Alkylation

    Science.gov (United States)

    Reddy, Aravind T.; Lakshmi, Sowmya P.; Muchumarri, Ramamohan R.; Reddy, Raju C.

    2016-01-01

    Nitrated fatty acids (NFAs), endogenous products of nonenzymatic reactions of NO-derived reactive nitrogen species with unsaturated fatty acids, exhibit substantial anti-inflammatory activities. They are both reversible electrophiles and peroxisome proliferator-activated receptor γ (PPARγ) agonists, but the physiological implications of their electrophilic activity are poorly understood. We tested their effects on inflammatory and emphysema-related biomarkers in alveolar macrophages (AMs) of smoke-exposed mice. NFA (10-nitro-oleic acid or 12-nitrolinoleic acid) treatment downregulated expression and activity of the inflammatory transcription factor NF-κB while upregulating those of PPARγ. It also downregulated production of inflammatory cytokines and chemokines and of the protease cathepsin S (Cat S), a key mediator of emphysematous septal destruction. Cat S downregulation was accompanied by decreased AM elastolytic activity, a major mechanism of septal destruction. NFAs downregulated both Cat S expression and activity in AMs of wild-type mice, but only inhibited its activity in AMs of PPARγ knockout mice, pointing to a PPARγ-independent mechanism of enzyme inhibition. We hypothesized that this mechanism was electrophilic S-alkylation of target Cat S cysteines, and found that NFAs bind directly to Cat S following treatment of intact AMs and, as suggested by in silico modeling and calculation of relevant parameters, elicit S-alkylation of Cys25 when incubated with purified Cat S. These results demonstrate that NFAs’ electrophilic activity, in addition to their role as PPARγ agonists, underlies their protective effects in chronic obstructive pulmonary disease (COPD) and support their therapeutic potential in this disease. PMID:27119365

  4. 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.

  5. 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.

  6. 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.)

  7. 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)

  8. Macrophages programmed by apoptotic cells inhibit epithelial-mesenchymal transition in lung alveolar epithelial cells via PGE2, PGD2, and HGF

    Science.gov (United States)

    Yoon, Young-So; Lee, Ye-Ji; Choi, Youn-Hee; Park, Young Mi; Kang, Jihee Lee

    2016-01-01

    Apoptotic cell clearance results in the release of growth factors and the action of signaling molecules involved in tissue homeostasis maintenance. Here, we investigated whether and how macrophages programmed by apoptotic cells inhibit the TGF-β1-induced Epithelial-mesenchymal transition (EMT) process in lung alveolar epithelial cells. Treatment with conditioned medium derived from macrophages exposed to apoptotic cells, but not viable or necrotic cells, inhibited TGF-β1-induced EMT, including loss of E-cadherin, synthesis of N-cadherin and α-smooth muscle actin, and induction of EMT-activating transcription factors, such as Snail1/2, Zeb1/2, and Twist1. Exposure of macrophages to cyclooxygenase (COX-2) inhibitors (NS-398 and COX-2 siRNA) or RhoA/Rho kinase inhibitors (Y-27632 and RhoA siRNA) and LA-4 cells to antagonists of prostaglandin E2 (PGE2) receptor (EP4 [AH-23848]), PGD2 receptors (DP1 [BW-A868C] and DP2 [BAY-u3405]), or the hepatocyte growth factor (HGF) receptor c-Met (PHA-665752), reversed EMT inhibition by the conditioned medium. Additionally, we found that apoptotic cell instillation inhibited bleomycin-mediated EMT in primary mouse alveolar type II epithelial cells in vivo. Our data suggest a new model for epithelial cell homeostasis, by which the anti-EMT programming of macrophages by apoptotic cells may control the progressive fibrotic reaction via the production of potent paracrine EMT inhibitors. PMID:26875548

  9. Macrophages programmed by apoptotic cells inhibit epithelial-mesenchymal transition in lung alveolar epithelial cells via PGE2, PGD2, and HGF.

    Science.gov (United States)

    Yoon, Young-So; Lee, Ye-Ji; Choi, Youn-Hee; Park, Young Mi; Kang, Jihee Lee

    2016-01-01

    Apoptotic cell clearance results in the release of growth factors and the action of signaling molecules involved in tissue homeostasis maintenance. Here, we investigated whether and how macrophages programmed by apoptotic cells inhibit the TGF-β1-induced Epithelial-mesenchymal transition (EMT) process in lung alveolar epithelial cells. Treatment with conditioned medium derived from macrophages exposed to apoptotic cells, but not viable or necrotic cells, inhibited TGF-β1-induced EMT, including loss of E-cadherin, synthesis of N-cadherin and α-smooth muscle actin, and induction of EMT-activating transcription factors, such as Snail1/2, Zeb1/2, and Twist1. Exposure of macrophages to cyclooxygenase (COX-2) inhibitors (NS-398 and COX-2 siRNA) or RhoA/Rho kinase inhibitors (Y-27632 and RhoA siRNA) and LA-4 cells to antagonists of prostaglandin E2 (PGE2) receptor (EP4 [AH-23848]), PGD2 receptors (DP1 [BW-A868C] and DP2 [BAY-u3405]), or the hepatocyte growth factor (HGF) receptor c-Met (PHA-665752), reversed EMT inhibition by the conditioned medium. Additionally, we found that apoptotic cell instillation inhibited bleomycin-mediated EMT in primary mouse alveolar type II epithelial cells in vivo. Our data suggest a new model for epithelial cell homeostasis, by which the anti-EMT programming of macrophages by apoptotic cells may control the progressive fibrotic reaction via the production of potent paracrine EMT inhibitors. PMID:26875548

  10. Sex differences in the response of the alveolar macrophage proteome to treatment with exogenous surfactant protein-A

    Directory of Open Access Journals (Sweden)

    Phelps David S

    2012-07-01

    Full Text Available Abstract Background Male wild type (WT C57BL/6 mice are less capable of clearing bacteria and surviving from bacterial pneumonia than females. However, if an oxidative stress (acute ozone exposure occurs before infection, the advantage shifts to males who then survive at higher rates than females. We have previously demonstrated that survival in surfactant protein-A (SP-A knockout (KO mice compared to WT was significantly reduced. Because the alveolar macrophage (AM is pivotal in host defense we hypothesized that SP-A and circulating sex hormones are responsible for these sex differences. We used 2D-DIGE to examine the relationship of sex and SP-A on the AM proteome. The role of SP-A was investigated by treating SP-A KO mice with exogenous SP-A for 6 and 18 hr and studying its effects on the AM proteome. Results We found: 1 less variance between KO males and females than between the WT counterparts by principal component analysis, indicating that SP-A plays a role in sex differences; 2 fewer changes in females when the total numbers of significantly changing protein spots or identified whole proteins in WT or 18 hr SP-A-treated males or females were compared to their respective KO groups; 3 more proteins with functions related to chaperones or protease balance and Nrf2-regulated proteins changed in response to SP-A in females than in males; and 4 the overall pattern of SP-A induced changes in actin-related proteins were similar in both sexes, although males had more significant changes. Conclusions Although there seems to be an interaction between sex and the effect of SP-A, it is unclear what the responsible mechanisms are. However, we found that several of the proteins that were expressed at significantly higher levels in females than in males in WT and/or in KO mice are known to interact with the estrogen receptor and may thus play a role in the SP-A/sex interaction. These include major vault protein, chaperonin subunit 2 (beta (CCT2, and Rho

  11. Mycoplasma bovis isolates recovered from cattle and bison (Bison bison) show differential in vitro effects on PBMC proliferation, alveolar macrophage apoptosis and invasion of epithelial and immune cells.

    Science.gov (United States)

    Suleman, Muhammad; Prysliak, Tracy; Clarke, Kyle; Burrage, Pat; Windeyer, Claire; Perez-Casal, Jose

    2016-04-15

    In the last few years, several outbreaks of pneumonia, systemically disseminated infection, and high mortality associated with Mycoplasma bovis (M. bovis) in North American bison (Bison bison) have been reported in Alberta, Manitoba, Saskatchewan, Nebraska, New Mexico, Montana, North Dakota, and Kansas. M. bovis causes Chronic Pneumonia and Polyarthritis Syndrome (CPPS) in young, stressed calves in intensively-managed feedlots. M. bovis is not classified as a primary pathogen in cattle, but in bison it appears to be a primary causative agent with rapid progression of disease with fatal outcomes and an average 20% mature herd mortality. Thus, there is a possibility that M. bovis isolates from cattle and bison differ in their pathogenicity. Hence, we decided to compare selected cattle isolates to several bison isolates obtained from clinical cases. We show differences in modulation of PBMC proliferation, invasion of trachea and lung epithelial cells, along with modulation of apoptosis and survival in alveolar macrophages. We concluded that some bison isolates showed less inhibition of cattle and bison PBMC proliferation, were not able to suppress alveolar macrophage apoptosis as efficiently as cattle isolates, and were more or less invasive than the cattle isolate in various cells. These findings provide evidence about the differential properties of M. bovis isolated from the two species and has helped in the selection of bison isolates for genomic sequencing. PMID:27016754

  12. Virulent and avirulent strains of equine arteritis virus induce different quantities of TNF-α and other proinflammatory cytokines in alveolar and blood-derived equine macrophages

    International Nuclear Information System (INIS)

    Equine arteritis virus (EAV) infects endothelial cells (ECs) and macrophages in horses, and many of the clinical manifestations of equine viral arteritis (EVA) reflect vascular injury. To further evaluate the potential role of EAV-induced, macrophage-derived cytokines in the pathogenesis of EVA, we infected cultured equine alveolar macrophages (AMphi), blood monocyte-derived macrophages (BMphi), and pulmonary artery ECs with either a virulent (KY84) or an avirulent (CA95) strain of EAV. EAV infection of equine AMphi, BMphi, and ECs resulted in their activation with increased transcription of genes encoding proinflammatory mediators, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α. Furthermore, the virulent KY84 strain of EAV induced significantly higher levels of mRNA encoding proinflammatory cytokines in infected AMphi and BMphi than did the avirulent CA95 strain. Treatment of equine ECs with the culture supernatants of EAV-infected AMphi and BMphi also resulted in EC activation with cell surface expression of E-selectin, whereas infection of ECs with purified EAV alone caused only minimal expression of E-selectin. The presence of TNF-α in the culture supernatants of EAV-infected equine AMphi, BMphi, and ECs was confirmed by bioassay, and the virulent KY84 strain of EAV induced significantly more TNF-α in all cell types than did the avirulent CA95 strain. Thus, the data indicate that EAV-induced, macrophage-derived cytokines may contribute to the pathogenesis of EVA in horses, and that the magnitude of the cytokine response of equine AMphi, BMphi, and ECs to EAV infection reflects the virulence of the infecting virus strain

  13. 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)

  14. Respiratory syncytial virus-like nanoparticle vaccination induces long-term protection without pulmonary disease by modulating cytokines and T-cells partially through alveolar macrophages

    Directory of Open Access Journals (Sweden)

    Lee YT

    2015-07-01

    Full Text Available Young-Tae Lee,1,* Eun-Ju Ko,1,2,* Hye Suk Hwang,1,2 Jong Seok Lee,1,3 Ki-Hye Kim,1 Young-Man Kwon,1 Sang-Moo Kang1,2 1Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, 2Department of Biology, Georgia State University, Atlanta, GA, USA; 3National Institute of Biological Resources, Incheon, South Korea *These authors contributed equally to this work Abstract: The mechanisms of protection against respiratory syncytial virus (RSV are poorly understood. Virus-like nanoparticles expressing RSV glycoproteins (eg, a combination of fusion and glycoprotein virus-like nanoparticles [FG VLPs] have been suggested to be a promising RSV vaccine candidate. To understand the roles of alveolar macrophages (AMs in inducing long-term protection, mice that were 12 months earlier vaccinated with formalin-inactivated RSV (FI-RSV or FG VLPs were treated with clodronate liposome prior to RSV infection. FI-RSV immune mice with clodronate liposome treatment showed increases in eosinophils, plasmacytoid dendritic cells, interleukin (IL-4+ T-cell infiltration, proinflammatory cytokines, chemokines, and, in particular, mucus production upon RSV infection. In contrast to FI-RSV immune mice with severe pulmonary histopathology, FG VLP immune mice showed no overt sign of histopathology and significantly lower levels of eosinophils, T-cell infiltration, and inflammatory cytokines, but higher levels of interferon-γ, which are correlated with protection against RSV disease. FG VLP immune mice with depletion of AMs showed increases in inflammatory cytokines and chemokines, as well as eosinophils. The results in this study suggest that FG nanoparticle vaccination induces long-term protection against RSV and that AMs play a role in the RSV protection by modulating eosinophilia, mucus production, inflammatory cytokines, and T-cell infiltration. Keywords: alveolar macrophage, nanoparticle vaccine, VLP, FI-RSV, RSV disease

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

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    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.

  16. 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

  17. Phagocytosis in vitro and intracellular survival rates of R and S forms of Pseudomonas pseudomalley in alveolar macrophages from whole-body gamma-irradiated guinea pigs

    International Nuclear Information System (INIS)

    A study was conducted to investigate the changes in the number of alveolar macrophages (AM), their phagocytosis activity and the intracellular killing effect. Two bacterial strains were used: Ps. pseudomonallei R15 and S7. Guinea pigs of both sexes received whole-body gamma irradiation (2 Gy, 4 x 0.5 Gy and 0.5 Gy; 92.5 rad/min). The macrophages were obtained by the method of Myrvik et al. on days 1, 3, 7, 15 and 30 after irradiation. The smallest applied dose reduced the AM number during the first 7 days and on day 30 it was higher than that of the controls. The sublethal dose of 2 Gy applied acutely led to a marked decrease in the number of AM; the same dose, obtained in fractions (4 x 0.5 Gy), had smaller effect. The phagocytic activity of the AM showed an inhibition both for the two bacterial strains, as follows: for 2 Gy dose it was inhibited until about day 15; for 0.5 Gy dose - until day 3, after which it rose and on day 30 the phagocytic number and phagocytic index was higher than those of the controls. Results for the fractionated dose (4 x 0.5 Gy) were similar to those for acute application. Intracellular survival test showed that melioidosis bacteria reproduced actively during the first 7 days after the single 2 Gy irradiation and during the first 3 days after the fractionated 2 Gy treatment. The intracellular bacterial mechanisms of the AM were appreciably damaged immediately after the irradiation depending on the dose. Comparing the results with similar data regarding rats, mice and peritoneal macrophages, it was concluded, that both R and S forms survived better in AM from guinea pigs irradiated with sublethal dose of gamma rays

  18. 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. PMID:26526351

  19. 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

  20. 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

  1. 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.

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

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    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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Pulmonary alveolar proteinosis

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    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.

  8. 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

  9. 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.

  10. 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...

  11. 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

  12. 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+.

  13. 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

  14. Transcription analysis on response of porcine alveolar macrophages to co-infection of the highly pathogenic porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Li, Bin; Du, Luping; Xu, Xiangwei; Sun, Bing; Yu, Zhengyu; Feng, Zhixin; Liu, Maojun; Wei, Yanna; Wang, Haiyan; Shao, Guoqing; He, Kongwang

    2015-01-22

    Porcine respiratory disease complex (PRDC) is of great concern economically, for swine producers worldwide. Co-infections with porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (Mhp) are considered the major causative agents of PRDC, and responsible for mass mortality in pigs. Nevertheless, the molecular mechanisms underlying the host factors involved in pathogenesis and persistent infection have not been clearly established because of a lack of information regarding host responses following co-infection. In the current study, high throughput cDNA microarray assays were employed to evaluate host responses of porcine alveolar macrophages (PAM) to co-infection with highly pathogenic PRRSV (HP-PRRSV) and Mhp. A total of 2152 and 1760 genes were identified as being differentially expressed between the control group and PRRSV+Mhp co-infected group at 6 and 15 h post infection, respectively. The DE genes were involved in many vital functional classes, including inflammatory response, immune response, apoptosis, defense response, signal transduction. The pathway analysis demonstrated that the most significant pathways were associated with chemokine signaling pathway, cytokine, TLR, RLR and NLR signaling pathways and Jak-STAT signaling pathway. STRING analysis demonstrated that IL-1β is an integral gene in co-infections with PRRSV and Mhp. The present study is the first to document the response of PAMs to co-infection with HP-PRRSV and Mhp. The observed gene expression profile could help with the screening of potential host agents for reducing the prevalence of co-infections, and to further develop our understanding of the molecular pathogenesis associated with PRRSV and Mhp co-infection in pigs. PMID:25445346

  15. 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.

  16. Bulky PAH-DNA induced by exposure of a co-culture model of human alveolar macrophages and embryonic epithelial cells to atmospheric particulate pollution

    International Nuclear Information System (INIS)

    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/g), inorganic (Fe, AI, Ca, Na, K, Mg, Pb, etc.) and organic compounds (PAHs, etc.). 32P 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: EC50 = 74.63 μg/mL and L132: LC-5-0 = 75.36 μg/mL). Exposure to desorbed particles (MA: C1= 61.11 μg/mL and L132 : C2 = 61.71 μg/mL) and B[a]P (1 μM) 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 they were competent in terms of metabolic activation of PAHs. The DNA

  17. Regulation of toll-like receptors 3, 7 and 9 in porcine alveolar macrophages by different genotype 1 strains of porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Kuzemtseva, Liudmila; de la Torre, Eugenia; Martín, Gerard; Soldevila, Ferran; Ait-Ali, Tahar; Mateu, Enric; Darwich, Laila

    2014-04-15

    The toll-like receptors (TLRs) play an important role in the innate host defense against pathogens. Endosomal TLRs, TLR3, TLR7/8, and TLR9 are involved in antiviral responses by promoting the production of antiviral cytokines such as type I interferons. Porcine reproductive and respiratory syndrome (PRRS) is an important disease causing economically high losses to the swine industry worldwide and caused by a single stranded positive sense RNA virus, known as PRRS virus (PRRSV). Studies focused on the interaction between PRRSV and TLRs are scarce. The aim of the present study was to evaluate the expression of TLR3, TLR7 and TLR9 in porcine alveolar macrophages (PAM) infected with different genotype 1 PRRSV strains previously sequenced and characterized by their ability to induce TNF-α: 3262 (TNF-α inducer), 3267 (TNF-α not inducer) and an attenuated vaccine strain (strain Deventer, PorcilisPRRS, Merck) that replicates scarcely in PAM. PAM were infected with the different PRRSV strains (at 0.1 multiplicity of infection) for 48 h or mock-stimulated with PAM supernatants. Cells were collected at different time-points (0 h, 6 h, 12 h, 24 h, 36 h, 48 h) to determine the kinetics of viral replication by quantitative RT-PCR (qRT-PCR) and the expression of TLR3, 7 and 9 by qRT-PCR, flow cytometry and indirect immunofluorescence assay. Although infection with PRRSV did not affect significantly relative levels of any TLR mRNA transcript (normalized to β-actin expression), this infection resulted in significant differences in the proportion of cells expressing TLR3. Thus, in PAM infected with PRRSV strain 3262 the proportion of TLR3+ cells significantly increased from 24h compared with the controls; in contrast strain 3267 resulted in a lower proportion of TLR3+ PAM. Interestingly, strain 3262 replicate to lower levels than 3267 at comparable post-inoculation times. For strain DV, the results indicated that this strain did not replicate substantially in PAM and did not

  18. 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

  19. 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

  20. 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 and...... accumulated in type II alveolar epithelial cells, lacking CFTR. P. aeruginosa organisms were rarely present in inflamed alveoli. CONCLUSIONS: Chronic inflammation and remodeling is present in alveolar tissues of the CF lung and needs to be addressed by anti-inflammatory therapies....

  1. 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

  2. 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...

  3. 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.

  4. 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

  5. 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...

  6. 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.

  7. Influence of heavy-metal-containing dusts on the release of plateled-activating factor (PAF) by alveolar macrophages. Final report; Einfluss von schwermetallhaltigen Staeuben auf die Freisetzung von Platelet-Activating Factor (PAF) durch Alveolarmakrophagen. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Gercken, G.; Froemming, G.; Mueller, I.M.

    1993-05-01

    The research project investigated the possibility for activating rabbit and bovine alveolar macrophages by quartz- and heavy-metal-containing dust. The formation of platelet activating factor (PAF) was used as a biochemical parameter. For comparison, human monocytes, monocytes differentiated as macrophages and granulocytes were additionally investigated. The results permit the conclusion that the formation of PAF is linked to the particle structure of the respective dust, not so much to the chemical condition of particle surface. In the case of heavy-metal containing dust, the inhibition of PAF synthesis by the heavy metals is not to be excluded. (orig./vhe) [Deutsch] In dem Forschungsprojekt wurde die Aktivierbarkeit von Kaninchen- und Rinderalveolarmakrophagen durch Quarz- und schwermetallhaltige Staeube untersucht. Als biochemischer Parameter wurde die Platelet-Activating-Factor (PAF) - Bildung herangezogen. Zum Vergleich wurden zusaetzlich humane Monocyten, zu Makrophagen ausdifferenzierte Monocyten und Granulocyten untersucht. Aufgrund der Ergebnisse kann davon ausgegangen werden, dass die PAF-Bildung mit der Partikelstruktur der einzelnen Staeube und weniger mit der chemischen Beschaffenheit der Partikeloberflaeche zusammenhaengt. Bei schwermetallhaltigen Staeuben ist eine Inhibierung der PAF-Synthese durch die Schwermetalle nicht auszuschliessen. (orig./vhe)

  8. 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...

  9. Gene expression profiling of human alveolar macrophages infected by B. anthracis spores demonstrates TNF-α and NF-κb are key components of the innate immune response to the pathogen

    Directory of Open Access Journals (Sweden)

    Hurst Robert E

    2009-09-01

    Full Text Available Abstract Background Bacillus anthracis, the etiologic agent of anthrax, has recently been used as an agent of bioterrorism. The innate immune system initially appears to contain the pathogen at the site of entry. Because the human alveolar macrophage (HAM plays a key role in lung innate immune responses, studying the HAM response to B. anthracis is important in understanding the pathogenesis of the pulmonary form of this disease. Methods In this paper, the transcriptional profile of B. anthracis spore-treated HAM was compared with that of mock-infected cells, and differentially expressed genes were identified by Affymetrix microarray analysis. A portion of the results were verified by Luminex protein analysis. Results The majority of genes modulated by spores were upregulated, and a lesser number were downregulated. The differentially expressed genes were subjected to Ingenuity Pathway analysis, the Database for Annotation, Visualization and Integrated Discovery (DAVID analysis, the Promoter Analysis and Interaction Network Toolset (PAINT and Oncomine analysis. Among the upregulated genes, we identified a group of chemokine ligand, apoptosis, and, interestingly, keratin filament genes. Central hubs regulating the activated genes were TNF-α, NF-κB and their ligands/receptors. In addition to TNF-α, a broad range of cytokines was induced, and this was confirmed at the level of translation by Luminex multiplex protein analysis. PAINT analysis revealed that many of the genes affected by spores contain the binding site for c-Rel, a member of the NF-κB family of transcription factors. Other transcription regulatory elements contained in many of the upregulated genes were c-Myb, CP2, Barbie Box, E2F and CRE-BP1. However, many of the genes are poorly annotated, indicating that they represent novel functions. Four of the genes most highly regulated by spores have only previously been associated with head and neck and lung carcinomas. Conclusion The

  10. 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...

  11. 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...

  12. 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 ...

  13. Increased alveolar plasminogen activator in early asbestosis

    Energy Technology Data Exchange (ETDEWEB)

    Cantin, A.; Allard, C.; Begin, R.

    1989-03-01

    Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure of the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of alveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos-exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS) or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity were measured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 +/- 17.3 versus 41.1 +/- 7.2 U/10(5) AM-24 h, p less than 0.05) as was the BAL fluid PA activity (674.9 +/- 168.4 versus 81.3 +/- 19.7 U/mg alb-24 h, p less than 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p less than 0.005), AM PA activity (p less than 0.02), and BAL PA activity (p less than 0.001) compared to the control group.

  14. Deep Learning of Orthographic Representations in Baboons

    OpenAIRE

    Thomas Hannagan; Ziegler, Johannes C.; Stéphane Dufau; Joël Fagot; Jonathan Grainger

    2014-01-01

    What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords [1]. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels) of letter strings onto binary word/nonword responses. We show that th...

  15. 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...

  16. 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...

  17. 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

  18. 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.

  19. 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.

  20. Physico-chemical properties of quartz from industrial manufacturing and its cytotoxic effects on alveolar macrophages: The case of green sand mould casting for iron production.

    Science.gov (United States)

    Di Benedetto, Francesco; Gazzano, Elena; Tomatis, Maura; Turci, Francesco; Pardi, Luca A; Bronco, Simona; Fornaciai, Gabriele; Innocenti, Massimo; Montegrossi, Giordano; Muniz Miranda, Maurizio; Zoleo, Alfonso; Capacci, Fabio; Fubini, Bice; Ghigo, Dario; Romanelli, Maurizio

    2016-07-15

    Industrial processing of materials containing quartz induces physico-chemical modifications that contribute to the variability of quartz hazard in different plants. Here, modifications affecting a quartz-rich sand during cast iron production, have been investigated. Composition, morphology, presence of radicals associated to quartz and reactivity in free radical generation were studied on a raw sand and on a dust recovered after mould dismantling. Additionally, cytotoxicity of the processed dust and ROS and NO generation were evaluated on MH-S macrophages. Particle morphology and size were marginally affected by casting processing, which caused only a slight increase of the amount of respirable fraction. The raw sand was able to catalyze OH and CO2(-) generation in cell-free test, even if in a lesser extent than the reference quartz (Min-U-Sil), and shows hAl radicals, conventionally found in any quartz-bearing raw materials. Enrichment in iron and extensive coverage with amorphous carbon were observed during processing. They likely contributed, respectively, to increasing the ability of processed dust to release CO2- and to suppressing OH generation respect to the raw sand. Carbon coverage and repeated thermal treatments during industrial processing also caused annealing of radiogenic hAl defects. Finally, no cellular responses were observed with the respirable fraction of the processed powder. PMID:27015375

  1. 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, ...

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Nitrogen dioxide effects on alveolar macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Acton, J.D.; Myrvik, Q.N.

    1972-01-01

    Rabbits were exposed to 5, 15, 25, or 50 ppM NO/sub 2/ for 3 h. Some had been previously injected intratracheally with parainfluenza-3 virus. Resistance of cells washed from lungs to new viral challenge was measured. Fifteen ppM NO/sub 2/ greater reduced induced-resistance. Fifteen ppM also reduced phagocytosis of BCG vaccine. Fifty ppM significantly increased O/sub 2/ consumption but 25 ppM did not. The increase in glucose-1-C was significant at 50 ppM.

  7. 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

  8. Animal models of bronchopulmonary dysplasia. The preterm baboon models

    OpenAIRE

    Yoder, Bradley A.; Coalson, Jacqueline J.

    2014-01-01

    Much of the progress in improved neonatal care, particularly management of underdeveloped preterm lungs, has been aided by investigations of multiple animal models, including the neonatal baboon (Papio species). In this article we highlight how the preterm baboon model at both 140 and 125 days gestation (term equivalent 185 days) has advanced our understanding and management of the immature human infant with neonatal lung disease. Not only is the 125-day baboon model extremely relevant to the...

  9. 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

  10. Preweaning food intake influences the adiposity of young adult baboons.

    OpenAIRE

    Lewis, D. S.; Bertrand, H A; McMahan, C.A.; McGill, H. C.; Carey, K D; Masoro, E J

    1986-01-01

    The hypothesis that preweaning nutrition influences adult fat cell number and adiposity was tested in baboons. Newborn baboons were fed Similac formulas with caloric densities of 40.5 kcal (underfed), 67.5 kcal (fed normally), and 94.5 kcal (overfed) per 100 g formula. From weaning (16 wk) until necropsy at 5 yr of age all baboons were fed the same diet. At necropsy, fat cell number and fat cell size in 10 fat depots were measured. Female baboons overfed as infants had markedly greater fat de...

  11. 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.

  12. Polonium metabolism in adult female baboons

    Energy Technology Data Exchange (ETDEWEB)

    Fellman, A. (Malcolm Pirnie, Inc., Cranbury, NJ (United States)); Ralston, L. (S. Cohen Associates, Inc., McLean, VA (United States)); Hickman, D. (Lawrence Livermore National Lab., CA (United States)); Ayres, L.; Cohen, N. (New York Univ. Medical Center, Tuxedo, NY (United States))

    1994-02-01

    The biokinetics of polonium in nonhuman primates (Papio anubis) has been studied after intravenous injection of [sup 210]Po citrate. The urinary excretion of polonium in the baboon could be described by a single exponential function with a half-time of 15.6 days. Excretion fractions of polonium were found to be markedly different from those reported for other species, including humans. Polonium-210 was found to be distributed throughout the soft tissues of the baboon with 29% of the injected polonium being deposited in liver, 7% in kidneys and 0.6 in spleen. Retention of polonium in all tissues exhibited single exponential functions; however, the biological half-times were variable, ranging from 15 to 50 days. 23 refs., 9 figs., 10 tabs.

  13. Deep learning of orthographic representations in baboons.

    Science.gov (United States)

    Hannagan, Thomas; Ziegler, Johannes C; Dufau, Stéphane; Fagot, Joël; Grainger, Jonathan

    2014-01-01

    What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels) of letter strings onto binary word/nonword responses. We show that the networks' highest levels of representations were indeed sensitive to letter combinations as postulated in our previous research. The model also captured the key empirical findings, such as generalization to novel words, along with some intriguing inter-individual differences. The present work shows the merits of deep learning networks that can simulate the whole processing chain all the way from the visual input to the response while allowing researchers to analyze the complex representations that emerge during the learning process. PMID:24416300

  14. Deep learning of orthographic representations in baboons.

    Directory of Open Access Journals (Sweden)

    Thomas Hannagan

    Full Text Available What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels of letter strings onto binary word/nonword responses. We show that the networks' highest levels of representations were indeed sensitive to letter combinations as postulated in our previous research. The model also captured the key empirical findings, such as generalization to novel words, along with some intriguing inter-individual differences. The present work shows the merits of deep learning networks that can simulate the whole processing chain all the way from the visual input to the response while allowing researchers to analyze the complex representations that emerge during the learning process.

  15. Characterization of semen from olive baboons.

    Science.gov (United States)

    Amboka, J N O; Mwethera, P G

    2003-12-01

    Electroejaculation is an accepted method of semen collection from non-human primates and is typically performed using direct penile or rectal probe electro-stimulation. Six mature male olive baboons (Papio anubis) were subjected to rectal probe electro-stimulation procedure that yielded 65 usable ejaculates in 69 attempts over a period of 16 weeks. The four non-usable ejaculates consisted of seminal fluid without sperm cells and thus were not analysed. The analysis of ejaculate volume, concentration, % motility, liquefaction times, and morphology in this study has provided information on the quality of semen samples. It is anticipated that this analysis will provide valuable information for male fertility studies and the development of an in vitro fertilization (IVF) system in the olive baboon as a model for human IVF. PMID:14641787

  16. 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。

  17. 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.

  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. 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

  1. Taxonomy Icon Data: hamadryas baboon [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available hamadryas baboon Papio hamadryas Chordata/Vertebrata/Mammalia/Theria/Eutheria/Primate Papio_hamadry...as_L.png Papio_hamadryas_NL.png Papio_hamadryas_S.png Papio_hamadryas_NS.png http://bioscien...cedbc.jp/taxonomy_icon/icon.cgi?i=Papio+hamadryas&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Papio+hamadry...as&t=NL http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Papio+hamadryas&...t=S http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Papio+hamadryas&t=NS http://togodb.biosciencedbc.jp/togodb/view/taxonomy_icon_comment_en?species_id=186 ...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. Assessment of metacognitive monitoring and control in baboons (Papio papio).

    Science.gov (United States)

    Malassis, Raphaëlle; Gheusi, Gilles; Fagot, Joël

    2015-11-01

    Metacognition refers to the ability of an organism to evaluate its states of knowledge (metacognitive monitoring) and engage in appropriate information-seeking behaviors when a lack of knowledge is detected (metacognitive control). This study assessed metacognitive monitoring and control in three Guinea baboons (Papio papio). Monkeys were required to report on a touchscreen the location of two target stimuli that had previously appeared briefly on a grid. They could either respond directly or use a "Repeat" key providing an opportunity to repeat the target stimuli. In Experiment 1, the baboons used the Repeat key more frequently in difficult trials and transferred this use of the key to novel conditions. Two baboons showed higher accuracy when they declined using the key compared to Baseline trials in which the key was not available, suggesting accurate metacognitive monitoring judgments. The same two baboons were consistently faster at reporting the targets' locations after a repetition of the stimulus. In Experiment 2, the baboons had to choose between two Repeat keys, one for each target. Two baboons showed a preference for repeating the presentation of the less visible target, suggesting that they identified what information they lack. Overall, results support the hypothesis of metacognitive monitoring in baboons, and also provide limited evidence for metacognitive control. We propose that tests requiring subjects to choose between several metacognitive responses in computerized tasks provide a suitable new approach for studying targeted information-seeking behaviors in animals. PMID:26232908

  8. 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.

  9. Complement sequestration in ischemic baboon myocardium

    International Nuclear Information System (INIS)

    Complement-mediated myocardial tissue injury following ischemia has proposed. In the present study, sequestration of radiolabeled human C5 was estimated in baboon myocardial tissue samples obtained 24 hr following ligation of the left anterior descending coronary artery (n=5 baboons). 125I-C5 and 131I-albumin were intravenously administered 24 hr prior to the ligation procedure; 99T-albumin was injected just prior to sacrifice and used to estimate tissue blood volume. Alternating myocardial tissue samples were evaluated for creatine kinase (CK) content after homogenization or for histology after fixation in neutral buffered formalin. 99Tc, 125I, and 131I were determined in all samples. Both C5 and albumin were sequestered in formalin-fixed tissues. No 131I-albumin was retained in any pellet following homogenization whereas, 125I-C5 was present in tissue pellets obtained from ischemic regions. 125I-C5 bound to myocardium was correlated to the extent of the tissue injury, i.e., as myocardial CK decreased, 125I-C5 sequestration increased. Thus, C5 accumulates in ischemic myocardium, and, in contrast to albumin which is present as a consequence of tissue edema following tissue injury, appears to be tissue-bound

  10. Bortezomib, C1-inhibitor and plasma exchange do not prolong the survival of multi-transgenic GalT-KO pig kidney xenografts in baboons.

    Science.gov (United States)

    Le Bas-Bernardet, S; Tillou, X; Branchereau, J; Dilek, N; Poirier, N; Châtelais, M; Charreau, B; Minault, D; Hervouet, J; Renaudin, K; Crossan, C; Scobie, L; Takeuchi, Y; Diswall, M; Breimer, M E; Klar, N; Daha, M R; Simioni, P; Robson, S C; Nottle, M B; Salvaris, E J; Cowan, P J; d'Apice, A J F; Sachs, D H; Yamada, K; Lagutina, I; Duchi, R; Perota, A; Lazzari, G; Galli, C; Cozzi, E; Soulillou, J-P; Vanhove, B; Blancho, G

    2015-02-01

    Galactosyl-transferase KO (GalT-KO) pigs represent a potential solution to xenograft rejection, particularly in the context of additional genetic modifications. We have performed life supporting kidney xenotransplantation into baboons utilizing GalT-KO pigs transgenic for human CD55/CD59/CD39/HT. Baboons received tacrolimus, mycophenolate mofetil, corticosteroids and recombinant human C1 inhibitor combined with cyclophosphamide or bortezomib with or without 2-3 plasma exchanges. One baboon received a control GalT-KO xenograft with the latter immunosuppression. All immunosuppressed baboons rejected the xenografts between days 9 and 15 with signs of acute humoral rejection, in contrast to untreated controls (n = 2) that lost their grafts on days 3 and 4. Immunofluorescence analyses showed deposition of IgM, C3, C5b-9 in rejected grafts, without C4d staining, indicating classical complement pathway blockade but alternate pathway activation. Moreover, rejected organs exhibited predominantly monocyte/macrophage infiltration with minimal lymphocyte representation. None of the recipients showed any signs of porcine endogenous retrovirus transmission but some showed evidence of porcine cytomegalovirus (PCMV) replication within the xenografts. Our work indicates that the addition of bortezomib and plasma exchange to the immunosuppressive regimen did not significantly prolong the survival of multi-transgenic GalT-KO renal xenografts. Non-Gal antibodies, the alternative complement pathway, innate mechanisms with monocyte activation and PCMV replication may have contributed to rejection. PMID:25612490

  11. 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.

  12. 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

  13. 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.

  14. Microscopic anatomy of the baboon (Papio hamadryas) adrenal medulla.

    OpenAIRE

    al-Lami, F; Carmichael, S W

    1991-01-01

    Adrenal medullas of 2 baboons perfused with formaldehyde/glutaraldehyde and tannic acid were studied by light and electron microscopy. Tissues were postfixed in OsO4. This procedure allows identification of noradrenaline cells on the basis of a selective reaction of glutaraldehyde with noradrenaline vesicles. As positive control for noradrenaline cells, similarly treated mouse adrenal medullas were also examined. Light microscopic examination of thick sections of baboon medullas did not show ...

  15. Feto-placental adaptations to maternal obesity in the baboon

    OpenAIRE

    Farley, Darren; Tejero, Maria E; Comuzzie, Anthony G.; Higgins, Paul B.; Cox, Laura; Werner, Sherry L.; Jenkins, Susan L.; Li, Cun; Choi, Jaehyek; Dick, Edward J.; Hubbard, Gene B.; Frost, Patrice; Dudley, Donald D.; Ballesteros, Brandon; Wu, Guoyao

    2009-01-01

    Maternal obesity is present in 20–34% of pregnant women and has been associated with both intrauterine growth restriction and large-for-gestational age fetuses. While fetal and placental functions have been extensively studied in the baboon, no data are available on the effect of maternal obesity on placental structure and function in this species. We hypothesize that maternal obesity in the baboon is associated with a maternal inflammatory state and induces structural and functional changes ...

  16. 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

  17. Salmonella enterica Serovars Typhimurium and Dublin Can Lyse Macrophages by a Mechanism Distinct from Apoptosis

    OpenAIRE

    Watson, Patricia R.; Gautier, Anne V.; Paulin, Sue M.; Bland, A. Patricia; Jones, Philip W.; Wallis, Timothy S.

    2000-01-01

    Salmonella enterica serovars Typhimurium and Dublin lysed primary bovine alveolar macrophages and immortalized J774.2 macrophage-like cells in the absence of either the morphological changes or DNA fragmentation characteristic of apoptosis. Macrophage lysis was dependent on a subset of caspases and an intact sipB gene.

  18. 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...

  19. 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.

  20. 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...

  1. Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids

    NARCIS (Netherlands)

    Bunt, JEH; Carnielli, VP; Seidner, [No Value; Ikegami, M; Wattimena, JLD; Sauer, PJJ; Jobe, AH; Zimmermann, LJI

    1999-01-01

    We studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. The newborn baboons were intubated, treated

  2. What baboons can (not) tell us about natural language grammars.

    Science.gov (United States)

    Poletiek, Fenna H; Fitz, Hartmut; Bocanegra, Bruno R

    2016-06-01

    Rey et al. (2012) present data from a study with baboons that they interpret in support of the idea that center-embedded structures in human language have their origin in low level memory mechanisms and associative learning. Critically, the authors claim that the baboons showed a behavioral preference that is consistent with center-embedded sequences over other types of sequences. We argue that the baboons' response patterns suggest that two mechanisms are involved: first, they can be trained to associate a particular response with a particular stimulus, and, second, when faced with two conditioned stimuli in a row, they respond to the most recent one first, copying behavior they had been rewarded for during training. Although Rey et al. (2012) 'experiment shows that the baboons' behavior is driven by low level mechanisms, it is not clear how the animal behavior reported, bears on the phenomenon of Center Embedded structures in human syntax. Hence, (1) natural language syntax may indeed have been shaped by low level mechanisms, and (2) the baboons' behavior is driven by low level stimulus response learning, as Rey et al. propose. But is the second evidence for the first? We will discuss in what ways this study can and cannot give evidential value for explaining the origin of Center Embedded recursion in human grammar. More generally, their study provokes an interesting reflection on the use of animal studies in order to understand features of the human linguistic system. PMID:26026382

  3. Absorption of biliary cobalamin in baboons following total gastrectomy

    International Nuclear Information System (INIS)

    Absorption of radiolabeled cobalamin in baboons was assessed by whole body counting. Retention of biliary cobalamin and an aqueous solution of cyanocobalamin was measured in normal baboons and in baboons after total gastrectomy by using 57Co-labeled biliary cobalamin and 58C0-cyanocobalamin, with and without baboon gastric juice containing intrinsic factor. Radiolabeled biliary cobalamin was obtained by intravenous injection of 57Co-cyanocobalamin in baboons and collection of bile through a cannula placed in the common bile duct. Cobalamin absorption was not completely abolished by gastrectomy and biliary cobalamin was better retained than cyanocobalamin; intrinsic factor enhanced absorption of both forms. After gastrectomy there was steady depletion of liver and serum cobalamin levels, which ceased after a new equilibrium was reached between a progressively diminishing cobalamin loss and the impaired but significant residual level of absorption. These studies in the nonhuman primate provide further information concerning the enterohepatic circulation of cobalamin and suggest that the form of cobalamin in bile may be more readily absorbed than is cyanocobalamin or that bile itself may have an enhancing effect on cobalamin absorption. The data also suggest that physiologically significant amounts of cobalamin may be absorbed in the absence of a gastric source of intrinsic factor

  4. 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

  5. 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

  6. 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

  7. The Baboon (Papio spp. as a Model of Human Ebola Virus Infection

    Directory of Open Access Journals (Sweden)

    Gary L.White

    2012-10-01

    Full Text Available Baboons are susceptible to natural Ebola virus (EBOV infection and share 96% genetic homology with humans. Despite these characteristics, baboons have rarely been utilized as experimental models of human EBOV infection to evaluate the efficacy of prophylactics and therapeutics in the United States. This review will summarize what is known about the pathogenesis of EBOV infection in baboons compared to EBOV infection in humans and other Old World nonhuman primates. In addition, we will discuss how closely the baboon model recapitulates human EBOV infection. We will also review some of the housing requirements and behavioral attributes of baboons compared to other Old World nonhuman primates. Due to the lack of data available on the pathogenesis of Marburg virus (MARV infection in baboons, discussion of the pathogenesis of MARV infection in baboons will be limited.

  8. Metabolism of bupropion by baboon hepatic and placental microsomes

    OpenAIRE

    Wang, Xiaoming; Abdelrahman, Doaa R.; Fokina, Valentina M.; Hankins, Gary D.V.; AHMED, Mahmoud S.; Nanovskaya, Tatiana N.

    2011-01-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 µM, Vmax 258 ± 32 pmol mg protein−1 min−1), however the formation of OH-...

  9. 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.

  10. 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.

  11. 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...

  12. 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 ...

  13. 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.

  14. 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

  15. 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

  16. Plutonium gastrointestinal absorption by adults baboons

    International Nuclear Information System (INIS)

    Gastrointestinal absorption of plutonium was investigated in baboons after ingestion of plutonium solution (oxidation states III; IV; V; VI), and plutonium incorporated in soya bean and winkles. We studied the effects of oxidation state and ingested mass for masses ranging from 0.35 μg to 51.6 x 10+3 μg (4 x 10-2 to 7776 μg of plutonium per kg of body weight). No clear increase in plutonium retention was shown for concentrations of plutonium smaller than 1 μg/kg. From 1 μg/kg to 1 mg/kg no effects of mass or oxidation state was observed and the mean fractional retention value was 10-4. For ingested masses higher than 1 mg/kg the fractional retention values respectively increased for Pu(V) and Pu(III) to (0.9 + 0.2) x 10-2 and (7.4+ 4.1) x 10-4 of the ingested mass. This increase might be due to the weak hydrolysis of these oxidation states which would increase gastrointestinal absorption by decrease of hydroxide formation. The fraction of plutonium retained after ingestion of soya bean was (3.0 + 0.5) x 10-4 about 3 fold higher than the value for 238 Pu nitrate solution. No clear increase in plutonium retention was shown after ingestion of winkles containing 238 Pu. In conclusion, except for high masses of ingested Pu, the retention of which could reach 1% of the ingested dose, our results show that the gastrointestinal transfer factor of 10-4 proposed by ICRP for gastrointestinal absorption of soluble form of Pu is acceptable, but 10-3 would provide better safety margin

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Inherently analog quantity representations in olive baboons (Papio anubis

    Directory of Open Access Journals (Sweden)

    JessicaFrancineCantlon

    2013-05-01

    Full Text Available Strong evidence indicates that non-human primates possess a numerical representation system, but the inherent nature of that system is still debated. Two cognitive mechanisms have been proposed to account for non-human primate numerical performance: (1 a discrete object-file system limited to quantities <4, and (2 an analog system which represents quantities comparatively but is limited by the ratio between two quantities. To test the underlying nature of non-human primate quantification, we asked eight experiment -naive olive baboons (Papio anubis to discriminate between number pairs containing small (<4, large (>4, or span (small vs. large numbers of food items presented simultaneously or sequentially. The prediction from the object-file hypothesis is that baboons will only accurately choose the larger quantity in small pairs, but not large or span pairs. Conversely, the analog system predicts that baboons will be successful with all numbers, and that success will be dependent on numerical ratio. We found that baboons successfully discriminated all pair types at above chance levels. In addition, performance significantly correlated with the ratio between the numerical values. Although performance was better for simultaneous trials than sequential trials, evidence favoring analog numerical representation emerged from both conditions, and was present even in the first exposure to number pairs. Together, these data favor the interpretation that a single, coherent analog representation system underlies spontaneous quantitative abilities in primates.

  2. 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 ...

  3. 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

  4. 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...

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. Mortality in Captive Baboons with Seizures: A New Model for SUDEP?

    OpenAIRE

    Szabó, C. Ákos; Knape, Koyle D.; Leland, M. Michelle; Feldman, Jake; McCoy, Karin J. M.; HUBBARD Gene B.; Williams, Jeff T.

    2009-01-01

    As the baboon is a model of primary generalized epilepsy, we were interested in mortality of captive animals with a history of witnessed seizures. Causes of natural death were investigated in 46 seizure baboons (SZ) and 78 nonepileptic controls (CTL), all of which underwent a complete pathological examination at the Southwest Foundation for Biomedical Research (SFBR) in San Antonio. SZ animals died at a younger age than the control baboons (p

  10. Baboon Model of Generalized Epilepsy: Continuous Intracranial Video-EEG Monitoring with Subdural Electrodes

    OpenAIRE

    Szabó, C. Ákos; Salinas, Felipe S.; Leland, M Michelle; Caron, Jean-Louis; Hanes, Martha A.; Knape, Koyle D.; Xie, Dongbin; Williams, Jeff T.

    2012-01-01

    The baboon provides a natural non-human primate model for photosensitive, generalized epilepsy. This study describes an implantation procedure for the placement of subdural grid and strip electrodes for continuous video-EEG monitoring in the epileptic baboon to evaluate the generation and propagation of ictal and interictal epileptic discharges. Subdural grid, strip and depth electrodes were implanted in six baboons, targeting brain regions that were activated in functional neuroimaging studi...

  11. Detection and Experimental Transmission of a Novel Babesia Isolate in Captive Olive Baboons (Papio cynocephalus anubis)

    OpenAIRE

    Reichard, Mason V; Gray, Kristene M; Van Den Bussche, Ronald A.; d'Offay, Jean M; White, Gary L.; Simecka, Christine M; Wolf, Roman F.

    2011-01-01

    Babesia spp. are tick-transmitted apicomplexan hemoparasites that infect mammalian red blood cells. Our purpose was to determine the prevalence of Babesia infection in a colony of captive baboons and to evaluate potential experimental routes of the transmission of the hemoparasite. DNA was extracted from the blood of baboons and tested for infection with Babesia by PCR and primers that amplify the 18s rRNA gene of the parasite. The overall prevalence of infection of Babesia in the baboon popu...

  12. Craniofacial Trauma as a Clinical Marker of Seizures in a Baboon Colony

    OpenAIRE

    Szabó, C. Ákos; Knape, Koyle D.; Leland, M. Michelle; Bauer, Cassondra; Williams, Jeff T.

    2014-01-01

    Baboons provide a natural model of epilepsy. However, spontaneous seizures are usually sporadic, brief, and may not be observed. We hypothesized that various types of craniofacial trauma (CFT) may serve as reliable markers for epilepsy. We evaluated the type, demographics, and clinical significance of CFT in a large baboon colony. CFT was categorized according to somatotopic location, propensity to recur, and association with witnessed seizures or abnormal EEG findings. We divided the baboons...

  13. Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids

    OpenAIRE

    Bunt, Jan Erik; Carnielli, Virgilio; Seidner, S.R.; Ikegami, M; Wattimena, Josias; Sauer, Pieter; Jobe, Alan; Zimmermann, Luc

    1999-01-01

    textabstractWe studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. The newborn baboons were intubated, treated with surfactant, and ventilated for 6 d. They received a 24-h infusion with the stable isotope [U-(13)C]glucose as precursor for the synthesis of palmitic acid in surfactant phosphatidy...

  14. 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...

  15. Electroejaculated Baboon (Papio anubis) Sperm Requires a Higher Dosage of Pentoxifylline to Enhance Motility

    OpenAIRE

    Cseh, Sandor; Chan, Philip J.; Corselli, Johannah; Bailey, Leonard L.

    2000-01-01

    Purpose: Sperm collected by electroejaculation often showpoor motility. The objective was to determine whether theaddition of the phosphodiesterase inhibitor, pentoxifylline,would stimulate electroejaculated baboon sperm motility.

  16. 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.

  17. Macrophage uptake of cylindrical microparticles investigated with correlative microscopy.

    OpenAIRE

    Tscheka, Clemens; Hittinger, Marius; Lehr, Claus-Michael; Schneider-Daum, Nicole; Schneider, Marc

    2015-01-01

    Cylindrical particles offer the opportunity to develop controlled and sustained release systems for the respiratory tract. One reason is that macrophages can phagocyte such particles only from either of the two ends. We investigated the uptake behaviour of murine alveolar macrophages incubated with elongated submicron-structured particles. For that purpose, fluorescent model silica nanoparticles were interconnected with the biocompatible polysaccharide agarose, building up cylindrical particl...

  18. Gastrointestinal transfer of neptunium (V) in newborn baboons: preliminary results

    International Nuclear Information System (INIS)

    To measure gastrointestinal neptunium absorption, baboons aged from 17 hours to 26 days were gavaged with an oral dose of 0.002 ug/kg of neptunium-239 nitrate. Absorption ranged from 3.71 to 0.113 per cent of the gavaged dose which was, 88 to 3 times higher than the values for adults. This range was reduced to 41 to 3 when doubtful results were discarded because of possible lung contamination. Absorption was expressed in terms of retention per animal at killing since collection of urine and faeces from neonates was not possible. For the same animals the skeleton/liver ratio of the neptunium burden rose continuously in the 26 dav-old baboon and reached twice the mean adult value

  19. Treponema infection associated with genital ulceration in wild baboons.

    Science.gov (United States)

    Knauf, S; Batamuzi, E K; Mlengeya, T; Kilewo, M; Lejora, I A V; Nordhoff, M; Ehlers, B; Harper, K N; Fyumagwa, R; Hoare, R; Failing, K; Wehrend, A; Kaup, F J; Leendertz, F H; Mätz-Rensing, K

    2012-03-01

    The authors describe genital alterations and detailed histologic findings in baboons naturally infected with Treponema pallidum. The disease causes moderate to severe genital ulcerations in a population of olive baboons (Papio hamadryas anubis) at Lake Manyara National Park in Tanzania. In a field survey in 2007, 63 individuals of all age classes, both sexes, and different grades of infection were chemically immobilized and sampled. Histology and molecular biological tests were used to detect and identify the organism responsible: a strain similar to T pallidum ssp pertenue, the cause of yaws in humans. Although treponemal infections are not a new phenomenon in nonhuman primates, the infection described here appears to be strictly associated with the anogenital region and results in tissue alterations matching those found in human syphilis infections (caused by T pallidum ssp pallidum), despite the causative pathogen's greater genetic similarity to human yaws-causing strains. PMID:21411621

  20. 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.

  1. 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...

  2. 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).

  3. 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.

  4. 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.



  5. 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

  6. Genetic integration of molar cusp size variation in baboons

    OpenAIRE

    Koh, Christina; BATES, ELIZABETH; Broughton, Elizabeth; Do, Nicholas T.; Fletcher, Zachary; Mahaney, Michael C.; Hlusko, Leslea J.

    2010-01-01

    Many studies of primate diversity and evolution rely on dental morphology for insight into diet, behavior, and phylogenetic relationships. Consequently, variation in molar cusp size has increasingly become a phenotype of interest. In 2007 we published a quantitative genetic analysis of mandibular molar cusp size variation in baboons. Those results provided more questions than answers, as the pattern of genetic integration did not fit predictions from odontogenesis. To follow up, we expanded o...

  7. Cross-placental transfer of 2434Cm in the baboon

    International Nuclear Information System (INIS)

    An adult female baboon was injected with 1.36 μCi 2434Cm approximately four months after the onset of pregnancy. Forty-five days subsequent to the injection, the fetus was delivered by Caesarean section and the individual organs assayed for their 2434Cm contents. The soft tissues, placenta and skeleton were found to contain 0.03, 1.11, and 0.42% respectively of the mother's body burden

  8. 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

  9. 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.

  10. Antelope Predation by Nigerian Forest Baboons: Ecological and Behavioural Correlates.

    Science.gov (United States)

    Sommer, Volker; Lowe, Adriana; Jesus, Gonçalo; Alberts, Nienke; Bouquet, Yaëlle; Inglis, David M; Petersdorf, Megan; van Riel, Eelco; Thompson, James; Ross, Caroline

    2016-01-01

    Baboons are well studied in savannah but less so in more closed habitats. We investigated predation on mammals by olive baboons (Papio anubis) at a geographical and climatic outlier, Gashaka Gumti National Park (Nigeria), the wettest and most forested site so far studied. Despite abundant wildlife, meat eating was rare and selective. Over 16 years, baboons killed 7 bushbuck (Tragelaphus scriptus) and 3 red-flanked duiker (Cephalophus rufilatus), mostly still-lying 'parked' infants. Taking observation time into account, this is 1 predation per group every 3.3 months - far lower than at other sites. Some features of meat eating resemble those elsewhere; predation is opportunistic, adult males monopolize most prey, a targeted killing bite is lacking and begging or active sharing is absent. Carcass owners employ evasive tactics, as meat is often competed over, but satiated owners may tolerate others taking meat. Other features are unusual; this is only the second study site with predation records for bushbuck and the only one for red-flanked duiker. The atypical prey and rarity of eating mammals probably reflects the difficulty of acquiring prey animals when vegetation cover is dense. Our data support the general prediction of the socioecological model that environments shape behavioural patterns, while acknowledging their intraspecific or intrageneric plasticity. PMID:27287424

  11. Detective mice assess relatedness in baboons using olfactory cues.

    Science.gov (United States)

    Célérier, Aurélie; Huchard, Elise; Alvergne, Alexandra; Féjan, Delphine; Plard, Floriane; Cowlishaw, Guy; Raymond, Michel; Knapp, Leslie A; Bonadonna, Francesco

    2010-05-01

    The assessment of relatedness may be crucial in the evolution of socio-sexual behaviour, because it can be associated with fitness benefits mediated by both nepotism and inbreeding avoidance. In this context, one proposed mechanism for kin recognition is 'phenotype matching'; animals might compare phenotypic similarities between themselves and others in order to assess the probability that they are related. Among cues potentially used for kin discrimination, body odours constitute interesting candidates that have been poorly investigated in anthropoid primates so far, because of a mixture of theoretical considerations and methodological/experimental constraints. In this study, we used an indirect approach to examine the similarity in odour signals emitted by related individuals from a natural population of chacma baboons (Papio ursinus). For that purpose, we designed an innovative behavioural tool using mice olfactory abilities in a habituation-discrimination paradigm. We show that: (i) mice can detect odour differences between individuals of same sex and age class in another mammal species, and (ii) mice perceive a higher odour similarity between related baboons than between unrelated baboons. These results suggest that odours may play a role in both the signalling of individual characteristics and of relatedness among individuals in an anthropoid primate. The 'biological olfactometer' developed in this study offers new perspectives to the exploration of olfactory signals from a range of species. PMID:20400623

  12. 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 ...

  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. Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids

    NARCIS (Netherlands)

    J.E.H. Bunt (Jan Erik); V.P. Carnielli (Virgilio); S.R. Seidner; M. Ikegami; J.L.D. Wattimena (Josias); P.J.J. Sauer (Pieter); A.H. Jobe (Alan); L.J.I. Zimmermann (Luc)

    1999-01-01

    textabstractWe studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. Th

  16. Exposure of surfactant protein A to ozone in vitro and in vivo impairs its interactions with alveolar cells

    Energy Technology Data Exchange (ETDEWEB)

    Oosting, R.S.; Van Iwaarden, J.F.; Van Bree, L.; Verhoef, J.; Van Golde, L.M.; Haagsman, H.P. (Laboratory of Veterinary Biochemistry, Utrecht University (Netherlands))

    1992-01-01

    This study focused on the question of whether exposure of surfactant protein A (SP-A) to ozone affected properties of this protein that may be involved in regulating alveolar type II cell and alveolar macrophage functions. In vitro exposure of human or canine SP-A to ozone reduced the ability of this protein to inhibit phorbol-ester induced secretion of (3H)phosphatidylcholine by alveolar type II cells in culture. Ozone-exposed human SP-A showed a decreased ability to enhance phagocytosis of herpes simplex virus and to stimulate superoxide anion production by alveolar macrophages. Experiments with elastase showed that ozone-exposed canine SP-A was more susceptible to proteolysis. A conformational change of the protein could underlie this phenomenon. Surfactant isolated from ozone-exposed rats (0.4 ppm ozone for 12 h) was also less able to stimulate superoxide anion production by alveolar macrophages than surfactant from control rats, which suggested that SP-A in vivo was also susceptible to ozone. The results of this study suggest that SP-A-alveolar cell interactions can be inhibited by ozone exposure, which may contribute to the toxicity of ozone in the lungs.

  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. 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

  19. 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

  20. 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...

  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. 5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons.

    OpenAIRE

    DESIMONE, J.; Heller, P; Hall, L; Zwiers, D

    1982-01-01

    In an attempt to stimulate Hb F synthesis in baboons by means other than erythropoietic stress, we considered the possibility that an agent that inhibits methylation of CpG sequences in DNA may be effective. 5-Azacytidine, a cytosine analogue that cannot be methylated, is such an agent. Animals whose packed red cell volume was maintained at approximately 20% by bleeding were given 10 daily intravenous injections of the drug (6 mg/kg) in 12 days. Hb F levels in these animals started to increas...

  4. Failure to label baboon milk intrinsically with iron

    International Nuclear Information System (INIS)

    The widely held belief that 50% of the iron in human milk is absorbed is based on studies that have used an extrinsic radioactive iron tag. To determine the validity of an extrinsic tag, it is necessary to label the milk intrinsically with one isotope and to compare absorption of this isotope with absorption of another isotope added as the extrinsic tag. We chose the baboon as a model and infused 59Fe intravenously. In each of three attempts we failed to label the milk intrinsically

  5. [18F]haloperidol binding in baboon brain in vivo

    International Nuclear Information System (INIS)

    The binding of [18F]haloperidol to dopamine D2 and to sigma recognition sites in baboon brain was examined using positron emission tomography (PET). Studies were performed at baseline and after treatment with either haloperidol (to evaluate saturability), (+)-butaclamol (which has specificity for dopamine D2 receptors) or (-)-butaclamol (which has specificity for sigma sites). Binding was widespread. Treatment with (-)-butaclamol had no effect, whereas (+)-butaclamol selectively reduced the uptake in striatum. Haloperidol increased the clearance rate from all brain regions. These results indicate that the binding profile of [18F]haloperidol does not permit the selective examination of either dopamine D2 or sigma sites using PET

  6. 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...

  7. 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...

  8. 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.

  9. 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

  10. 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.

  11. Resolvins Decrease Oxidative Stress Mediated Macrophage and Epithelial Cell Interaction through Decreased Cytokine Secretion

    OpenAIRE

    Cox, Ruan; Phillips, Oluwakemi; Fukumoto, Jutaro; Fukumoto, Itsuko; Tamarapu Parthasarathy, Prasanna; Mandry, Maria; Cho, Young; Lockey, Richard; Kolliputi, Narasaiah

    2015-01-01

    Background Inflammation is a key hallmark of ALI and is mediated through ungoverned cytokine signaling. One such cytokine, interleukin-1beta (IL-1β) has been demonstrated to be the most bioactive cytokine in ALI patients. Macrophages are the key players responsible for IL-1β secretion into the alveolar space. Following the binding of IL-1β to its receptor, “activated” alveolar epithelial cells show enhanced barrier dysfunction, adhesion molecule expression, cytokine secretion, and leukocyte a...

  12. 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...

  13. Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia

    NARCIS (Netherlands)

    D.J. Janssen; V.P. Carnielli (Virgilio); P.E. Cogo (Paola); S.R. Seidner; I.H.I. Luijendijk; J.L.D. Wattimena (Josias); A.H. Jobe (Alan); L.J.I. Zimmermann (Luc)

    2002-01-01

    textabstractBecause minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing bronchopulmon

  14. Voxel-based morphometry in epileptic baboons: Parallels to human juvenile myoclonic epilepsy.

    Science.gov (United States)

    Szabó, C Ákos; Salinas, Felipe S

    2016-08-01

    The epileptic baboon represents a natural model for genetic generalized epilepsy (GGE), closely resembling juvenile myoclonic epilepsy (JME). Due to functional neuroimaging and pathological differences between epileptic (SZ+) and asymptomatic control (CTL) baboons, we expected structural differences in gray matter concentration (GMC) using voxel-based morphometry (VBM). Standard anatomical (MP-RAGE) MRI scans using a 3T Siemens TIM Trio (Siemens, Erlangen, Germany) were available in 107 baboons (67 females; mean age 16±6years) with documented clinical histories and scalp-electroencephalography (EEG) results. For neuroimaging, baboons were anesthetized with isoflurane 1% (1-1.5 MAC) and paralyzed with vecuronium (0.1-0.3mg/kg). Data processing and analysis were performed using FSL's VBM toolbox. GMC was compared between CTL and SZ+ baboons, epileptic baboons with interictal epileptic discharges on scalp EEG (SZ+/IED+), asymptomatic baboons with abnormal EEGs (SZ-/IED+), and IED+ baboons with (IED+/PS+) and without (IED+/PS-) photosensitivity, and the subgroups amongst themselves. Age and gender related changes in gray matter volumes were also included as confound regressors in the VBM analyses of each animal group. Significant increases in GMC were noted in the SZ+/IED+ subgroup compared to the CTL group, including bilaterally in the frontopolar, orbitofrontal and anterolateral temporal cortices, while decreases in GMC were noted in the right more than left primary visual cortices and in the specific nuclei of the thalamus, including reticular, anterior and medial dorsal nuclei. No significant differences were noted otherwise, except that SZ+/IED+ baboons demonstrated increased GMC in the globus pallidae bilaterally compared to the SZ-/IED+ group. Similar to human studies of JME, the epileptic baboons demonstrated GMC decreases in the thalami and occipital cortices, suggesting secondary injury due to chronic epilepsy. Cortical GMC, on the other hand, was increased

  15. Microdistribution of 2434Cm in the ovary of an adult baboon

    International Nuclear Information System (INIS)

    Studies are currently underway to define the distribution of 2434Cm in tissues of the adult baboon. The results of these investigations are not yet complete, however, the specific loci of deposition for curium in the ovary was of sufficient interest and contained dosimetric implications which warrant this preview of a more complete description. Therefore, a brief description of the autoradiographic results obtained in sections of the left ovary of a representative adult baboon injected with 2434Cm is presented

  16. Antibiotic-resistant bacteria in wild primates: increased prevalence in baboons feeding on human refuse.

    OpenAIRE

    Rolland, R M; Hausfater, G; Marshall, B.; Levy, S B

    1985-01-01

    We examined three groups of wild baboons (Papio cynocephalus) in Amboseli National Park, Kenya, to determine the prevalence of aerobic antibiotic-resistant fecal bacteria in nonhuman primates with and without contact with human refuse. Using standard isolation and replica plating techniques, we found only low numbers of antibiotic-resistant gram-negative enteric bacteria in two groups of baboons leading an undisturbed existence in their natural habitat and having limited or no contact with hu...

  17. Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia

    OpenAIRE

    Janssen, D.J.; Carnielli, Virgilio; Cogo, Paola; Seidner, S.R.; Luijendijk, I.H.I.; Wattimena, Josias; Jobe, Alan; Zimmermann, Luc

    2002-01-01

    textabstractBecause minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing bronchopulmonary dysplasia, using stable isotopes, radioactive isotopes, and direct pool size measurements. Eight ventilated premature baboons received (2)H-DPPC (dipalmitoyl phosphatidylcholine) on d 5 of life, and radioactive ...

  18. 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

  19. Age Effects on Transfer Index Performance and Executive Control in Baboons (Papio papio

    Directory of Open Access Journals (Sweden)

    JoëlFagot

    2014-03-01

    Full Text Available Reversal performance in the transfer index (TI task is known to improve from prosimians to apes, suggesting that this task is a marker of cognitive evolution within the primate taxa (Rumbaugh, 1970. However, the cognitive processes recruited by this task remain unclear. In the present study, 19 socially-housed baboons (Papio papio from 1.6 to 14.3 years were tested on a computerized version of the TI task, using an automated self-testing procedure. Age was a significant factor in the level of success, with the younger baboons outperforming the adults. The younger baboons also learned the pre-reversal discrimination faster and improved their post-reversal performance more rapidly than adult baboons. As the same baboons had been tested in previous studies on inhibitory control and cognitive flexibility tasks, comparison across tasks provide indicators of the underlying cognitive processes. Age variations in performance were similar between the TI task and in an adaptation of the Wisconsin Card Sorting Task measuring cognitive flexibility (Bonté, Flemming and Fagot, 2011. This contrasts previous results from a task requiring motor inhibitory control (Fagot, Bonté and Hopkins, 2013. Therefore, these findings suggest that cognitive flexibility was a central component of the cognitive system that evolved within nonhuman primates. They also implicate a decline in executive control with age that begins during early adulthood in the baboon species.

  20. DSCR9 gene simultaneous expression in placental, testicular and renal tissues from baboon (papio hamadryas

    Directory of Open Access Journals (Sweden)

    Rodriguez-Sanchez Irám

    2012-06-01

    Full Text Available Abstract Background In 2002 Takamatsu and co-workers described the human DSCR9 gene and observed that it was transcriptionally active in human testicular tissue, but no protein was identified as a product of this transcript. Similar results were obtained in chimpanzee tissue. This gene has not been detected in species other than primates, suggesting that DSCR9 is exclusively found in these mammals. Results We report evidence of DSCR9 expression in placenta, testis and kidney of baboon (Papio hamadryas. We used primers specific for DSCR9 to amplify transcripts through reverse transcription (RT coupled to polymerase chain reaction (PCR. Furthermore, PCR was used to amplify the complete DSCR9 gene from genomic DNA from three baboons. We amplified and sequenced five overlapping segments that were assembled into the 3284 bp baboon DSCR9 gene, including the putative promoter and the entire transcriptional unit (5'-UTR, CDS and 3'-UTR. Conclusions The baboon DSCR9 gene is highly similar to the human counterpart. The isolated transcripts from baboon tissues (placenta, testis and kidney of three different baboons correspond to the human orthologous gene.

  1. 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.

  2. 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

  3. Fetal hemoglobin reactivation in baboon and man: a short perspective.

    Science.gov (United States)

    Lavelle, D; DeSimone, J; Heller, P

    1993-01-01

    Present concepts of the mechanism of reactivation of synthesis of fetal hemoglobin (HbF) in the adult under conditions of erythropoietic stress are briefly reviewed. Since HbF can be considered an effective natural antisickling agent, the reactivation of its synthesis in patients with sickle cell anemia as a desirable therapeutic goal has been extensively explored since the discovery in 1982 that 5-azacytidine increases HbF levels in the baboon. Hydroxyurea (HU) has become the most widely used agent, although its effectiveness in increasing HbF levels and the number of F cells is highly variable. Recent investigations are cited showing that other agents such as butyrate, and the addition of recombinant hemopoietic growth factors, such as erythropoietin and stem cell factor, especially in combination with HU, offer important therapeutic possibilities. Transacting nuclear proteins are briefly discussed as possibly having a future role in the efforts of stimulating gamma-chain synthesis. PMID:7677951

  4. A pacific culture among wild baboons: its emergence and transmission.

    Directory of Open Access Journals (Sweden)

    Robert M Sapolsky

    2004-04-01

    Full Text Available Reports exist of transmission of culture in nonhuman primates. We examine this in a troop of savanna baboons studied since 1978. During the mid-1980s, half of the males died from tuberculosis; because of circumstances of the outbreak, it was more aggressive males who died, leaving a cohort of atypically unaggressive survivors. A decade later, these behavioral patterns persisted. Males leave their natal troops at adolescence; by the mid-1990s, no males remained who had resided in the troop a decade before. Thus, critically, the troop's unique culture was being adopted by new males joining the troop. We describe (a features of this culture in the behavior of males, including high rates of grooming and affiliation with females and a "relaxed" dominance hierarchy; (b physiological measures suggesting less stress among low-ranking males; (c models explaining transmission of this culture; and (d data testing these models, centered around treatment of transfer males by resident females.

  5. 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.

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. True Fibroma of Alveolar Mucosa

    Directory of Open Access Journals (Sweden)

    Shankargouda Patil

    2014-01-01

    Full Text Available Benign fibrous overgrowths are often found in the oral cavity, almost always being reactive/irritational in nature. However, benign mesenchymal neoplasms of the fibroblasts are extremely uncommon. Here we report a case of “True Fibroma of Alveolar Mucosa” for its rarity.

  11. 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

  12. Metabolism and Disposition of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) in Baboons after Oral Administration: Comparison with Humans Reveals Marked Differences

    OpenAIRE

    Mueller, Melanie; Goodwin, Amy K.; Ator, Nancy A; McCann, Una D.; Ricaurte, George A.

    2011-01-01

    The baboon is potentially an attractive animal for modeling 3,4-methylenedioxymethamphetamine (MDMA) effects in humans. Baboons self-administer MDMA, are susceptible to MDMA neurotoxicity, and are suitable for positron emission tomography, the method most often used to probe for MDMA neurotoxicity in humans. Because pharmacokinetic equivalence is a key feature of a good predictive animal model, we compared the pharmacokinetics of MDMA in baboons and humans. Baboons were trained to orally cons...

  13. 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...

  14. 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...

  15. Modeling the effective connectivity of the visual network in healthy and photosensitive, epileptic baboons.

    Science.gov (United States)

    Ákos Szabó, C; Salinas, Felipe S; Li, Karl; Franklin, Crystal; Leland, M Michelle; Fox, Peter T; Laird, Angela R; Narayana, Shalini

    2016-05-01

    The baboon provides a model of photosensitive, generalized epilepsy. This study compares cerebral blood flow responses during intermittent light stimulation (ILS) between photosensitive (PS) and healthy control (CTL) baboons using H 2 (15) O-PET. We examined effective connectivity associated with visual stimulation in both groups using structural equation modeling (SEM). Eight PS and six CTL baboons, matched for age, gender and weight, were classified on the basis of scalp EEG findings performed during the neuroimaging studies. Five H 2 (15) O-PET studies were acquired alternating between resting and activation (ILS at 25 Hz) scans. PET images were acquired in 3D mode and co-registered with MRI. SEM demonstrated differences in neural connectivity between PS and CTL groups during ILS that were not previously identified using traditional activation analyses. First-level pathways consisted of similar posterior-to-anterior projections in both groups. While second-level pathways were mainly lateralized to the left hemisphere in the CTL group, they consisted of bilateral anterior-to-posterior projections in the PS baboons. Third- and fourth-level pathways were only evident in PS baboons. This is the first functional neuroimaging study used to model the photoparoxysmal response (PPR) using a primate model of photosensitive, generalized epilepsy. Evidence of increased interhemispheric connectivity and bidirectional feedback loops in the PS baboons represents electrophysiological synchronization associated with the generation of epileptic discharges. PS baboons demonstrated decreased model stability compared to controls, which may be attributed to greater variability in the driving response or PPRs, or to the influence of regions not included in the model. PMID:25749860

  16. 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

  17. 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.

  18. 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)

  19. Sex differences in the acoustic structure of vowel-like grunt vocalizations in baboons and their perceptual discrimination by baboon listeners

    Science.gov (United States)

    Rendall, Drew; Owren, Michael J.; Weerts, Elise; Hienz, Robert D.

    2004-01-01

    This study quantifies sex differences in the acoustic structure of vowel-like grunt vocalizations in baboons (Papio spp.) and tests the basic perceptual discriminability of these differences to baboon listeners. Acoustic analyses were performed on 1028 grunts recorded from 27 adult baboons (11 males and 16 females) in southern Africa, focusing specifically on the fundamental frequency (F0) and formant frequencies. The mean F0 and the mean frequencies of the first three formants were all significantly lower in males than they were in females, more dramatically so for F0. Experiments using standard psychophysical procedures subsequently tested the discriminability of adult male and adult female grunts. After learning to discriminate the grunt of one male from that of one female, five baboon subjects subsequently generalized this discrimination both to new call tokens from the same individuals and to grunts from novel males and females. These results are discussed in the context of both the possible vocal anatomical basis for sex differences in call structure and the potential perceptual mechanisms involved in their processing by listeners, particularly as these relate to analogous issues in human speech production and perception.

  20. Gastrointestinal absorption of plutonium and uranium in fed and fasted adult baboons and mice: application to humans

    International Nuclear Information System (INIS)

    Gastrointestinal (GI) absorption values of plutonium and uranium were determined in fed and fasted adult baboons and mice. For both baboons and mice, the GI absorptions of plutonium and uranium were 10 to 20 times higher in 24 h fasted animals than in fed ones. For plutonium, GI absorption values in baboons were almost identical to those in mice for both fed and fasted conditions, and values for fed animals agreed with estimates for humans. For uranium, GI absorption values in fed and fasted baboons were 6 to 7 times higher than those in mice, and agreed well with those fed and fasted humans. For one baboon that was not given its morning meal, plutonium absorption 2 h after the start of the active phase was the same as that in the 24 h fasted animals. In contrast, for baboons that received a morning meal, plutonium absorption did not rise to the value of 24 h fasted baboons even 8 h after the meal. We conclude that GI absorption values for plutonium and uranium in adult baboons are good estimates of the values in humans and that the values for the fasted condition should be used to set standards for oral exposure of persons in the workplace. (author)

  1. Mitochondrial genome analyses suggest multiple Trichuris species in humans, baboons, and pigs from different geographical regions

    DEFF Research Database (Denmark)

    Hawash, Mohamed B. F.; Andersen, Lee O.; Gasser, Robin B.;

    2015-01-01

    primates. METHODS AND FINDINGS: We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes of...

  2. S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis

    Directory of Open Access Journals (Sweden)

    Banzon Virryan

    2010-10-01

    Full Text Available Abstract Background S110 is a novel dinucleoside analog that could have advantages over existing DNA methyltransferase (DNMT inhibitors such as decitabine. A potential therapeutic role for S110 is to increase fetal hemoglobin (HbF levels to treat β-hemoglobinopathies. In these experiments the effect of S110 on HbF levels in baboons and its ability to reduce DNA methylation of the γ-globin gene promoter in vivo were evaluated. Methods The effect of S110 on HbF and γ-globin promoter DNA methylation was examined in cultured human erythroid progenitors and in vivo in the baboon pre-clinical model. S110 pharmacokinetics was also examined in the baboon model. Results S110 increased HbF and reduced DNA methylation of the γ-globin promoter in human erythroid progenitors and in baboons when administered subcutaneously. Pharmacokinetic analysis was consistent with rapid conversion of S110 into the deoxycytosine analog decitabine that binds and depletes DNA. Conclusion S110 is rapidly converted into decitabine, hypomethylates DNA, and induces HbF in cultured human erythroid progenitors and the baboon pre-clinical model.

  3. Schistosoma mansoni: parasitology and immunology of baboons vaccinated with irradiated cryopreserved schistosomula

    Energy Technology Data Exchange (ETDEWEB)

    Damian, R.T.; Powell, M.R.; Roberts, M.L. (Georgia Univ., Athens (USA). Dept. of Zoology); Clark, J.D. (Georgia Univ., Athens (USA). Lab. Animal Medicine); Stirewalt, M.A.; Lewis, F.A. (Biomedical Research Inst., Rockville, MD (USA))

    1985-06-01

    Young baboons (Papio cynocephalus) were vaccinated with ..gamma..-irradiated (500 Gy) cryopreserved Puerto Rican strain schistosomula of S. mansoni. Protection against heterologous, normal Kenyan Strain S. mansoni challenge infection was erratic and partial; and two putative correlates of immunity, reduced worm fecundity and change in worm location (anterior shift) were not observed. However, immunization of baboons with this vaccine resulted in a stimulated immune system. Both cellular and humoral anamnesis were demonstrable in vaccinated-challenged baboons. Schistosome infection-associated IgM hypergammaglobulinemia was also greatly reduced in vaccinated-challenged baboons. However IgG antibodies to adult, egg, and cercarial antigens were increased after challenge infection in preimmunized baboons. Vaccination appears to have resulted in a redirection of the immune system into anti-parasite channels, but this more specific immune response was insufficient to confer good protection against challenge infection in this experiment. The dampening effect of the vaccine on the hypergammaglobulinemia of schistosomiasis is another candidate for a possible ''anti-pathogenesis'' effect of irradiated schistosome larval vaccines.

  4. Schistosoma mansoni: parasitology and immunology of baboons vaccinated with irradiated cryopreserved schistosomula

    International Nuclear Information System (INIS)

    Young baboons (Papio cynocephalus) were vaccinated with γ-irradiated (500 Gy) cryopreserved Puerto Rican strain schistosomula of S. mansoni. Protection against heterologous, normal Kenyan Strain S. mansoni challenge infection was erratic and partial; and two putative correlates of immunity, reduced worm fecundity and change in worm location (anterior shift) were not observed. However, immunization of baboons with this vaccine resulted in a stimulated immune system. Both cellular and humoral anamnesis were demonstrable in vaccinated-challenged baboons. Schistosome infection-associated IgM hypergammaglobulinemia was also greatly reduced in vaccinated-challenged baboons. However IgG antibodies to adult, egg, and cercarial antigens were increased after challenge infection in preimmunized baboons. Vaccination appears to have resulted in a redirection of the immune system into anti-parasite channels, but this more specific immune response was insufficient to confer good protection against challenge infection in this experiment. The dampening effect of the vaccine on the hypergammaglobulinemia of schistosomiasis is another candidate for a possible ''anti-pathogenesis'' effect of irradiated schistosome larval vaccines. (author)

  5. Comparison of early mortality in baboons and dogs after inhalation of 239PuO2

    International Nuclear Information System (INIS)

    Results from experiments with baboons were compared with those from experiments with dogs to determine the relative sensitivity of the two species to early mortality from inhaled 239PuO2. To ensure a valid comparison of data developed at two laboratories, methodology differences were minimized by establishing a common pool of raw data, using the same computer programs to analyze the data, and standardizing assumptions regarding the calculation of plutonium concentration in lungs. Several comparison methods were used involving variations in estimating different parameters used in these calculations. Although nearly all comparisons suggested baboons were slightly more sensitive, none of the methods for comparing the relationship between dose and survival time showed consistently significant differences between baboons and dogs. Although the baboons were physiologically and morphologically immature when exposed to plutonium, whereas the dogs were mature, we concluded that adult baboons and dogs are similarly sensitive to the early effects of inhaled 239PuO2. Since only early mortality was considered in this comparison, the results do not apply to possible late effects caused by much lower levels of plutonium than were used in these experiments

  6. Human infants and baboons show the same pattern of handedness for a communicative gesture.

    Directory of Open Access Journals (Sweden)

    Helene Meunier

    Full Text Available To test the role of gestures in the origin of language, we studied hand preferences for grasping or pointing to objects at several spatial positions in human infants and adult baboons. If the roots of language are indeed in gestural communication, we expect that human infants and baboons will present a comparable difference in their pattern of laterality according to task: both should be more right-hand/left-hemisphere specialized when communicating by pointing than when simply grasping objects. Our study is the first to test both human infants and baboons on the same communicative task. Our results show remarkable convergence in the distribution of the two species' hand biases on the two kinds of tasks: In both human infants and baboons, right-hand preference was significantly stronger for the communicative task than for grasping objects. Our findings support the hypothesis that left-lateralized language may be derived from a gestural communication system that was present in the common ancestor of baboons and humans.

  7. Bomb-spike dating of a mummified baboon in Ludwig Cave, Namibia

    Directory of Open Access Journals (Sweden)

    Hodgins Greg

    2007-01-01

    Full Text Available In 1982 a mummified adult female baboon was discovered on a ledge in Ludwig Cave in Namibia. A toe bone was removed for dating in July 1995. AMS radiocarbon dating of bone collagen, tendon, and skin indicates a post-modern age. Application of the atomic bomb-spike calibration curve suggests death in late 1977 and an age at death of around 19 years. Baboons roost in the cave and the mummified female, along with a mummified juvenile male discovered in 2002 and three rotting corpses discovered in 1995, were probably chased by other baboons or by leopards down a ca. 6 m drop during the rainy season, and were unable to climb the steep and very slippery slope to escape. The large number of baboons trapped in the cave in less than 20 years, and mummification of two individuals on dry, dusty ledges in the cave, may explain why large numbers of baboon skeletons have been discovered in ancient bone breccias (up to 4 Ma old in a number of caves throughout Southern Africa.

  8. New data on the toxicity and translocation of inhaled 239PuO2 in baboons

    International Nuclear Information System (INIS)

    In 1973-1974, baboons were exposed to a polydispersed aerosol of 239PuO2, prepared at 10000C, at the Commissariat a l'Energie Atomique in France. The data published in 1978 for these baboons were used by Bair et al (1980), for comparison with those obtained in beagles exposed to 239PuO2 at the Pacific Northwest Laboratory, USA. Since our 1978 publication, 8 baboons have died or were killed by euthanasia when moribund, and 11 were still alive when the present report was drafted. Two of the eight baboons died of lung squamous cell carcinoma at 2171 and 2528 days respectively. The remaining 6 died of fibrosis, interstitial pneumonia or diseases unrelated to Pu toxicity. The relationship observed in the eight baboons between initial lung burden and survival time shows that their lifespan was longer than expected from the data curve based on the findings for the first 1000 days. However, this increased survival time was not observed if the lifespan was expressed as a function of the average lung burden. (author)

  9. Comparison of acute mortality in baboons and dogs after inhalation of 239PuO2

    International Nuclear Information System (INIS)

    Results from experiments with baboons were compared with those from experiments with dogs to determine the relative sensitivity of the two species to acute mortality from inhaled 239PuO2. To assure a valid comparison of data developed at two laboratories, methodology differences were minimized by establishing a common pool of raw data, using the same computer programs to analyze the data, and standardizing assumptions regarding the calculation of radiation doses to lungs. Several comparison methods were used involving variations in estimating different parameters such as the concentration of plutonium in the lungs. Although nearly all comparisons suggested baboons were slightly more sensitive, none of the methods for comparing the relationship between dose and survival time showed consistently significant differences between baboons and dogs. Although the baboons were physiologically and morphologically immature when exposed to plutonium, whereas the dogs were mature, it was concluded that adult baboons and dogs are similarly sensitive to the acute effects of inhaled 239PuO2. Since only acute mortality was considered in this comparison, the results do not apply to possible late effects caused by much lower levels of plutonium than were used in these experiments

  10. 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...

  11. 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...

  12. 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

  13. 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

  14. Distribution and retention of 2434Cm in the adult baboon

    International Nuclear Information System (INIS)

    The metabolism of 2434Cm-citrate was studied in six adult female baboons for up to 26 months post intravenous injection. In vivo measurements employing gamma scintillation detectors in conjunction with whole-body and partial-body counting techniques were used to estimate deposition and retention for the total body and specific organ sites. In addition, 2434Cm concentrations were measured in urine, feces, blood, and biopsy samples of liver. Curium-243,4 leaves the blood rapidly with 0.7% of the injected dose present in the blood at 24 hrs after injection. The primary sites of deposition are skeleton (approx. = 60%) and liver (approx. = 20%) at early times. The retention of 2434Cm in bone has a half-life of several years, while that in liver is approximately 40 days. Approximately 7% of the injected dose is excreted in the urine during the first 24 hrs. Curium-243,4 eliminated from the liver appears to be predominantly excreted with the feces as is the case for 241Am

  15. Wild chacma baboons (Papio ursinus) remember single foraging episodes.

    Science.gov (United States)

    Noser, Rahel; Byrne, Richard W

    2015-07-01

    Understanding animal episodic-like memory is important for tracing the evolution of the human mind. However, our knowledge about the existence and nature of episodic-like memory in non-human primates is minimal. We observed the behaviour of a wild male chacma baboon faced with a trade-off between protecting his stationary group from aggressive extra-group males and foraging among five out-of-sight platforms. These contained high-priority food at a time of natural food shortage. In 10 morning and eight evening trials, the male spontaneously visited the platforms in five and four different sequences, respectively. In addition, he interrupted foraging sequences at virtually any point on eight occasions, returning to the group for up to 2 h. He then visited some or all of the remaining platforms and prevented revisits to already depleted ones, apparently based on his memory for the previous foraging episode about food value, location, and time. Efficient use of memory allowed him to keep minimal time absent from his group while keeping food intake high. These findings support the idea that episodic-like memory offers an all-purpose solution to a wide variety of problems that require flexible, quick, yet precise decisions in situations arising from competition for food and mates in wild primates. PMID:25833223

  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. 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...

  18. 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.

  19. 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

  20. A non-Levy random walk in chacma baboons: what does it mean?

    Directory of Open Access Journals (Sweden)

    Cédric Sueur

    Full Text Available The Lévy walk is found from amoebas to humans and has been described as the optimal strategy for food research. Recent results, however, have generated controversy about this conclusion since animals also display alternatives to the Lévy walk such as the Brownian walk or mental maps and because movement patterns found in some species only seem to depend on food patches distribution. Here I show that movement patterns of chacma baboons do not follow a Lévy walk but a Brownian process. Moreover this Brownian walk is not the main process responsible for movement patterns of baboons. Findings about their speed and trajectories show that baboons use metal maps and memory to find resources. Thus the Brownian process found in this species appears to be more dependent on the environment or might be an alternative when known food patches are depleted and when animals have to find new resources.

  1. 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

  2. [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

  3. The metabolism and gastrointestinal absorption of neptunium and protactinium in adult baboons

    International Nuclear Information System (INIS)

    The metabolism of neptunium and protactinium was studied in adult female baboons following intravenous injection and intragastric intubation. Neptunium-239, Np-237, and Pa-233 were prepared as either citrate-buffer, nitrate, or bicarbonate solutions with oxidation states of (V) and (VI). Samples of blood, urine, feces and autopsy tissues were measured by gamma spectrometry. Retention of neptunium and protactinium was determined in vivo using whole and partial body gamma-scintillation spectrometry with [NaI-CsI(T1)] detectors. Fed and fasted baboons were administered solutions of Np(VI) bicarbonate (10/sup -8/ to 10/sup -1/ mg/kg) and Pa(V) citrate-buffer (10/sup -9/ mg/kg) by gavage. The gastrointestinal absorption value for neptunium in two fasted baboons, sacrificed at 1 day post administration, was determined to be 0.92 +- 0.04%. Of the total amount of neptunium absorbed, 52 +- 3% was retained in bone, 6 + 2% was in liver, and 42 +- 0.1% was excreted in urine. The metabolism of neptunium followed oral and iv administrations was found to be similar. This observation was also true for baboons which had received oral and iv doses of protactinium. A method was developed to estimate GI absorption values for both nuclides in baboons, which were not sacrificed, by comparison of activities present in bioassay samples after injection and gavage. Absorption values calculated by this method for neptunium and protactinium in fasted baboons were 1.8 +- 0.8% and 0.65 +- 0.01%, respectively. Values for fed animals were 1 to 2 orders of magnitude less than those for fasted animals. Further experiments are currently underway to evaluate this assay technique

  4. High Prevalence of Antibodies against the Bacterium Treponema pallidum in Senegalese Guinea Baboons (Papio papio.

    Directory of Open Access Journals (Sweden)

    Sascha Knauf

    Full Text Available The bacterium Treponema pallidum is known to cause syphilis (ssp. pallidum, yaws (ssp. pertenue, and endemic syphilis (ssp. endemicum in humans. Nonhuman primates have also been reported to be infected with the bacterium with equally versatile clinical manifestations, from severe skin ulcerations to asymptomatic. At present all simian strains are closely related to human yaws-causing strains, an important consideration for yaws eradication. We tested clinically healthy Guinea baboons (Papio papio at Parc National Niokolo Koba in south eastern Senegal for the presence of anti-T. pallidum antibodies. Since T. pallidum infection in this species was identified 50 years ago, and there has been no attempt to treat non-human primates for infection, it was hypothesized that a large number of West African baboons are still infected with simian strains of the yaws-bacterium. All animals were without clinical signs of treponematoses, but 18 of 20 (90% baboons tested positive for antibodies against T. pallidum based on treponemal tests. Yet, Guinea baboons seem to develop no clinical symptoms, though it must be assumed that infection is chronic or comparable to the latent stage in human yaws infection. The non-active character is supported by the low anti-T. pallidum serum titers in Guinea baboons (median = 1:2,560 versus serum titers that are found in genital-ulcerated olive baboons with active infection in Tanzania (range of medians among the groups of initial, moderate, and severe infected animals = 1:15,360 to 1:2.097e+7. Our findings provide evidence for simian infection with T. pallidum in wild Senegalese baboons. Potentially, Guinea baboons in West Africa serve as a natural reservoir for human infection, as the West African simian strain has been shown to cause sustainable yaws infection when inoculated into humans. The present study pinpoints an area where further research is needed to support the currently on-going second WHO led yaws eradication

  5. Bomb-spike dating of a mummified baboon in Ludwig Cave, Namibia

    OpenAIRE

    Hodgins Greg; Brook George A.; Marais Eugene

    2007-01-01

    In 1982 a mummified adult female baboon was discovered on a ledge in Ludwig Cave in Namibia. A toe bone was removed for dating in July 1995. AMS radiocarbon dating of bone collagen, tendon, and skin indicates a post-modern age. Application of the atomic bomb-spike calibration curve suggests death in late 1977 and an age at death of around 19 years. Baboons roost in the cave and the mummified female, along with a mummified juvenile male discovered in 2002 and three rotting corpses discovered i...

  6. High Prevalence of Antibodies against the Bacterium Treponema pallidum in Senegalese Guinea Baboons (Papio papio)

    Science.gov (United States)

    Knauf, Sascha; Barnett, Ulrike; Maciej, Peter; Klapproth, Matthias; Ndao, Ibrahima; Frischmann, Sieghard; Fischer, Julia; Zinner, Dietmar; Liu, Hsi

    2015-01-01

    The bacterium Treponema pallidum is known to cause syphilis (ssp. pallidum), yaws (ssp. pertenue), and endemic syphilis (ssp. endemicum) in humans. Nonhuman primates have also been reported to be infected with the bacterium with equally versatile clinical manifestations, from severe skin ulcerations to asymptomatic. At present all simian strains are closely related to human yaws-causing strains, an important consideration for yaws eradication. We tested clinically healthy Guinea baboons (Papio papio) at Parc National Niokolo Koba in south eastern Senegal for the presence of anti-T. pallidum antibodies. Since T. pallidum infection in this species was identified 50 years ago, and there has been no attempt to treat non-human primates for infection, it was hypothesized that a large number of West African baboons are still infected with simian strains of the yaws-bacterium. All animals were without clinical signs of treponematoses, but 18 of 20 (90%) baboons tested positive for antibodies against T. pallidum based on treponemal tests. Yet, Guinea baboons seem to develop no clinical symptoms, though it must be assumed that infection is chronic or comparable to the latent stage in human yaws infection. The non-active character is supported by the low anti-T. pallidum serum titers in Guinea baboons (median = 1:2,560) versus serum titers that are found in genital-ulcerated olive baboons with active infection in Tanzania (range of medians among the groups of initial, moderate, and severe infected animals = 1:15,360 to 1:2.097e+7). Our findings provide evidence for simian infection with T. pallidum in wild Senegalese baboons. Potentially, Guinea baboons in West Africa serve as a natural reservoir for human infection, as the West African simian strain has been shown to cause sustainable yaws infection when inoculated into humans. The present study pinpoints an area where further research is needed to support the currently on-going second WHO led yaws eradication campaign with

  7. Gastrointestinal absorption of plutonium, uranium and neptunium in fed and fasted adult baboons: Application to humans

    International Nuclear Information System (INIS)

    Gastrointestinal (GI) absorption values of plutonium, uranium, and neptunium were determined in fed and fasted adult baboons. A dual isotope method of determining GI absorption, which does not require animal sacrifice, was validated and shown to compare well with the sacrifice method (summation of oral isotope in urine with that in tissues at sacrifice). For all three elements, mean GI absorption values were significantly high (5- to 50-fold) in 24-hour (h)-fasted animals than in fed animals, and GI absorption values for baboons agreed well with those for humans

  8. 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...... dysfunction via a T-helper 2 (T(H)2) dominated alveolar inflammation with CD20 T-cell activation, induced by the chronic infection and showing a poor prognosis. There is great potential for treatment in transforming the T(H)2 into the more favorable T-helper 1 (T(H)1) response....

  9. Management of the alveolar cleft.

    Science.gov (United States)

    Santiago, Pedro E; Schuster, Lindsay A; Levy-Bercowski, Daniel

    2014-04-01

    Orthopedic and orthodontic management of patients born with clefts of the lip, alveolus and palate is based on the application of basic biomechanical principles adapted to the individualized cleft anatomy. This article focuses on orthopedic and orthodontic preparation for 2 stages of interdisciplinary orthodontic/surgical cleft care: presurgical infant orthopedics (nasoalveolar molding) for lip/alveolus/nasal surgical repair and maxillary arch preparation for secondary alveolar bone grafting. These preparatory stages of orthopedic/orthodontic therapy are undertaken with the goal of restoring normal anatomic relationships to assist the surgeon in providing the best possible surgical care. PMID:24607190

  10. Maternal obesity disrupts the methionine cycle in baboon pregnancy.

    Science.gov (United States)

    Nathanielsz, Peter W; Yan, Jian; Green, Ralph; Nijland, Mark; Miller, Joshua W; Wu, Guoyao; McDonald, Thomas J; Caudill, Marie A

    2015-11-01

    Maternal intake of dietary methyl-micronutrients (e.g. folate, choline, betaine and vitamin B-12) during pregnancy is essential for normal maternal and fetal methionine metabolism, and is critical for important metabolic processes including those involved in developmental programming. Maternal obesity and nutrient excess during pregnancy influence developmental programming potentially predisposing adult offspring to a variety of chronic health problems. In the present study, we hypothesized that maternal obesity would dysregulate the maternal and fetal methionine cycle. To test this hypothesis, we developed a nulliparous baboon obesity model fed a high fat, high energy diet (HF-HED) prior to and during gestation, and examined methionine cycle biomarkers (e.g., circulating concentrations of homocysteine, methionine, choline, betaine, key amino acids, folate, and vitamin B-12). Animals were group housed allowing full physical activity and social interaction. Maternal prepregnancy percent body fat was 5% in controls and 19% in HF-HED mothers, while fetal weight was 16% lower in offspring of HF-HED mothers at term. Maternal and fetal homocysteine were higher, while maternal and fetal vitamin B-12 and betaine were lower in the HF-HED group. Elevations in circulating maternal folate were evident in the HF-HED group indicating impaired folate metabolism (methyl-trap) as a consequence of maternal vitamin B-12 depletion. Finally, fetal methionine, glycine, serine, and taurine were lower in the HF-HED fetuses. These data show that maternal obesity disturbs the methionine cycle in primate pregnancy, providing a mechanism for the epigenetic changes observed among obese pregnant women and suggesting diagnostic and therapeutic opportunities in human pregnancies complicated by obesity. PMID:26537341

  11. 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.)

  12. 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.)

  13. Networked T cell death following macrophage infection by Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    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

  14. 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.)

  15. 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.)

  16. Chelation of curium in the adult baboon using Ca- and Zn-DTPA

    International Nuclear Information System (INIS)

    The effectiveness of Ca-DTPA in removing internally deposited Cm-243, 244 was tested in the baboon at 1.5 and 8-month intervals between injection of Cm-243, 244 and treatment. Four young adult female baboons were injected IV with the radionuclides in citrate form. Ca-DTPA was administered three times in five days on alternate days beginning at 1.5 months in one baboon and at 8 months in another. The two remaining control baboons were administered physiological saline only. In vivo counting was performed to determine the total body, skeletal, and liver retention before, during and after chelation therapy. All urine and feces were collected and the Cm-243, 244 content of each was determined daily. A comparison of the efficacy of chelate therapy with Cm-243, 244 and Am-241 when treatment was delayed for 1.5 months after Am-241 injection showed that Ca-DTPA is more effective in enhancing the excretion of established burdens of Cm-243, 244 than that of Am-241 by approximately 34 percent in the urine and 87 percent in the feces during the first seven days after initiation of therapy

  17. Immunization of baboons with Schistosoma mansoni cercariae attenuated by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Stek, M. Jr.; Minard, P.; Dean, D.A.; Hall, J.E.

    1981-06-26

    Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70%) and egg excretion rates (82%). These results support immunization as a potential method for schistosomiasis control.

  18. Immunization of Baboons with Schistosoma mansoni Cercariae attenuated by gamma irradiation

    International Nuclear Information System (INIS)

    Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70 percent) and egg excretion rates (82 percent). These results support immunization as a potential method for schistosomiasis control

  19. Immunization of baboons with Schistosoma mansoni cercariae attenuated by gamma irradiation

    International Nuclear Information System (INIS)

    Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70%) and egg excretion rates (82%). These results support immunization as a potential method for schistosomiasis control

  20. Immunization of Baboons with Schistosoma mansoni Cercariae attenuated by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Stek, M.; Minard, P.; Dean, D.A.; Hall, J.E.

    1981-06-01

    Studies on the efficacy of a vaccine against schistosomiasis in young baboons (Papio anubis) disclosed that immunization with Schistosoma mansoni cercariae attenuated by gamma irradiation induced significant protection against subsequent infection with normal, viable S. mansoni cercariae. Such immunization resulted in reduced worm burdens (70 percent) and egg excretion rates (82 percent). These results support immunization as a potential method for schistosomiasis control.

  1. The average baboon brain: MRI templates and tissue probability maps from 89 individuals.

    Science.gov (United States)

    Love, Scott A; Marie, Damien; Roth, Muriel; Lacoste, Romain; Nazarian, Bruno; Bertello, Alice; Coulon, Olivier; Anton, Jean-Luc; Meguerditchian, Adrien

    2016-05-15

    The baboon (Papio) brain is a remarkable model for investigating the brain. The current work aimed at creating a population-average baboon (Papio anubis) brain template and its left/right hemisphere symmetric version from a large sample of T1-weighted magnetic resonance images collected from 89 individuals. Averaging the prior probability maps output during the segmentation of each individual also produced the first baboon brain tissue probability maps for gray matter, white matter and cerebrospinal fluid. The templates and the tissue probability maps were created using state-of-the-art, freely available software tools and are being made freely and publicly available: http://www.nitrc.org/projects/haiko89/ or http://lpc.univ-amu.fr/spip.php?article589. It is hoped that these images will aid neuroimaging research of the baboon by, for example, providing a modern, high quality normalization target and accompanying standardized coordinate system as well as probabilistic priors that can be used during tissue segmentation. PMID:26975558

  2. Sarcoglycan complex in masseter and sternocleidomastoid muscles of baboons: an immunohistochemical study

    Directory of Open Access Journals (Sweden)

    G. Cutroneo

    2015-06-01

    Full Text Available The sarcoglycan complex consists of a group of single-pass transmembrane glycoproteins that are essential to maintain the integrity of muscle membranes. Any mutation in each sarcoglycan gene causes a series of recessive autosomal dystrophin-positive muscular dystrophies. Negative fibres for sarcoglycans have never been found in healthy humans and animals. In this study, we have investigated whether the social ranking has an influence on the expression of sarcoglycans in the skeletal muscles of healthy baboons. Biopsies of masseter and sternocleidomastoid muscles were processed for confocal immunohistochemical detection of sarcoglycans. Our findings showed that baboons from different social rankings exhibited different sarcoglycan expression profiles. While in dominant baboons almost all muscles were stained for sarcoglycans, only 55% of muscle fibres showed a significant staining. This different expression pattern is likely to be due to the living conditions of these primates. Sarcoglycans which play a key role in muscle activity by controlling contractile forces may influence the phenotype of muscle fibres, thus determining an adaptation to functional conditions. We hypothesize that this intraspecies variation reflects an epigenetic modification of the muscular protein network that allows baboons to adapt progressively to a different social status.

  3. 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...

  4. Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense Pathways in Rat Alveolar Type II Pneumocytes

    Directory of Open Access Journals (Sweden)

    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.

  5. [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

  6. 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

  7. Pleistocene aridification cycles shaped the contemporary genetic architecture of Southern African baboons.

    Directory of Open Access Journals (Sweden)

    Riashna Sithaldeen

    Full Text Available Plio-Pleistocene environmental change influenced the evolutionary history of many animal lineages in Africa, highlighting key roles for both climate and tectonics in the evolution of Africa's faunal diversity. Here, we explore diversification in the southern African chacma baboon Papio ursinus sensu lato and reveal a dominant role for increasingly arid landscapes during past glacial cycles in shaping contemporary genetic structure. Recent work on baboons (Papio spp. supports complex lineage structuring with a dominant pulse of diversification occurring 1-2Ma, and yet the link to palaeoenvironmental change remains largely untested. Phylogeographic reconstruction based on mitochondrial DNA sequence data supports a scenario where chacma baboon populations were likely restricted to refugia during periods of regional cooling and drying through the Late Pleistocene. The two lineages of chacma baboon, ursinus and griseipes, are strongly geographically structured, and demographic reconstruction together with spatial analysis of genetic variation point to possible climate-driven isolating events where baboons may have retreated to more optimum conditions during cooler, drier periods. Our analysis highlights a period of continuous population growth beginning in the Middle to Late Pleistocene in both the ursinus and the PG2 griseipes lineages. All three clades identified in the study then enter a state of declining population size (Nef through to the Holocene; this is particularly marked in the last 20,000 years, most likely coincident with the Last Glacial Maximum. The pattern recovered here conforms to expectations based on the dynamic regional climate trends in southern Africa through the Pleistocene and provides further support for complex patterns of diversification in the region's biodiversity.

  8. Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi.

    Science.gov (United States)

    Nyakundi, Ruth K; Nyamongo, Onkoba; Maamun, Jeneby; Akinyi, Mercy; Mulei, Isaac; Farah, Idle O; Blankenship, D'Arbra; Grimberg, Brian; Hau, Jann; Malhotra, Indu; Ozwara, Hastings; King, Christopher L; Kariuki, Thomas M

    2016-05-01

    Malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n = 8 each) and a schistosomiasis control group (n = 3) were infected with 500 Schistosoma mansoni cercariae. At 14 and 15 weeks postinfection, one group was given praziquantel to treat schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n = 8) were intravenously inoculated with 10(5) Plasmodium knowlesi parasites and monitored daily for development of severe malaria. A total of 81% of baboons exposed to chronic S. mansoni infection with or without praziquantel treatment survived malaria, compared to only 25% of animals infected with P. knowlesi only (P = 0.01). Schistosome-infected animals also had significantly lower parasite burdens (P = 0.004) than the baboons in the P. knowlesi-only group and were protected from severe anemia. Coinfection was associated with increased spontaneous production of interleukin-6 (IL-6), suggesting an enhanced innate immune response, whereas animals infected with P. knowlesi alone failed to develop mitogen-driven tumor necrosis factor alpha and IL-10, indicating the inability to generate adequate protective and balancing immunoregulatory responses. These results indicate that chronic S. mansoni attenuates the severity of P. knowlesi coinfection in baboons by mechanisms that may enhance innate immunity to malaria. PMID:26883586

  9. Natural killer cells in baboons and humans subjected to total lymphoid irradiation and subsequent renal transplantation

    International Nuclear Information System (INIS)

    This study investigates the functional ability and numbers of natural killer (NK) cells in peripheral blood of the chacma baboon and humans which were subjected to varying doses of total lymphoid irradiation (TLI) and subsequent renal transplantation. NK cell activity was determined by measuring the amount of 51Cr release from K562 target cells when placed in contact with baboon or human peripheral blood lymphocytes. The anti-human antibody Leu11b was shown to cross-react with determinants on baboon effector cells. Concomitant measurements of large granular lymphocytes (LGL) were also made. Normal values for NK cell activity Leu11b+ cells and LGL in the baboon were 73.4+-39.6 Vmax units, 6.8+-3.8% and 6.0+-3.2% respectively. After TLI, NK cell activity was elevated 3 to 4 fold of pre-TLI values and remained at these supranormal levels. The effects of surgery caused a transient depression of activity. Normal values for NK cell activity, Leu11b+ cells and LGL in humans were 280+-212 Vmax units, 6.7+-2.5% and 7.6+-2.5% respectively. A significant depression of NK cell activity was observed in renal allograft patients receiving combination doses of immunosuppressive drugs. Those patients that received tolerogenic doses of TLI prior to transplant followed by immunosuppressive drug regimens had a significant and persistent elevation of NK cell activity. Baboons and humans showed no relationship between NK cell function and Leu11b+ cells or LGL. The latter two parameters did not significantly change in response to TLI or transplantation. It was concluded that TLI gives rise to activated NK cells which results in elevated function unrelated to cell numbers. This dissertation has demonstrated that one advantage of TLI lies in the selective suppression of immunity - while graft tolerance is easily induced

  10. 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

  11. Experimental infections of baboons (Papio spp. and vervet monkeys (Cercopithecus aethiops with Trichinella zimbabwensis and successful treatment with ivermectin

    Directory of Open Access Journals (Sweden)

    S. Mukaratirwa

    2008-08-01

    Full Text Available Experimental Trichinella zimbabwensis infections were established in three baboons (Papios p.and four vervet monkeys (Cercopithecuase thiops and the clinical-pathological manifestations assessed. The infected animals showed clinical signs ranging from fever, diarrhoea, periorbitaol edema and muscular pain in varying degrees. One baboon became blind due to the infection. Levels of creatinine phosphokinase and lactated ehydrogenase increased to reach a peak on Day 42 post-infection(pifor both baboons and monkeys. Blood parameters such as packed cell volume, levels of red blood cells and white blood cells did not change significantly from the normal ranges except for the levels of eosinophils which peaked above the normal ranges at Day 28 and 56 pi in baboons and at Day 56 pi in monkeys.

  12. Inability to sustain intraphagolysosomal killing of Staphylococcus aureus predisposes to bacterial persistence in macrophages.

    Science.gov (United States)

    Jubrail, Jamil; Morris, Paul; Bewley, Martin A; Stoneham, Simon; Johnston, Simon A; Foster, Simon J; Peden, Andrew A; Read, Robert C; Marriott, Helen M; Dockrell, David H

    2016-01-01

    Macrophages are critical effectors of the early innate response to bacteria in tissues. Phagocytosis and killing of bacteria are interrelated functions essential for bacterial clearance but the rate-limiting step when macrophages are challenged with large numbers of the major medical pathogen Staphylococcus aureus is unknown. We show that macrophages have a finite capacity for intracellular killing and fail to match sustained phagocytosis with sustained microbial killing when exposed to large inocula of S. aureus (Newman, SH1000 and USA300 strains). S. aureus ingestion by macrophages is associated with a rapid decline in bacterial viability immediately after phagocytosis. However, not all bacteria are killed in the phagolysosome, and we demonstrate reduced acidification of the phagolysosome, associated with failure of phagolysosomal maturation and reduced activation of cathepsin D. This results in accumulation of viable intracellular bacteria in macrophages. We show macrophages fail to engage apoptosis-associated bacterial killing. Ultittop mately macrophages with viable bacteria undergo cell lysis, and viable bacteria are released and can be internalized by other macrophages. We show that cycles of lysis and reuptake maintain a pool of viable intracellular bacteria over time when killing is overwhelmed and demonstrate intracellular persistence in alveolar macrophages in the lungs in a murine model. PMID:26248337

  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. Fetal baboon sex specific outcomes in adipocyte differentiation at 0.9 gestation in response to moderate maternal nutrient reduction

    OpenAIRE

    Tchoukalova, Yourka D.; Krishnapuram, Rashmi; White, Ursula A.; Burk, David; Fang, Xiaobing; Nijland, Mark J.; Nathanielsz, Peter W.

    2013-01-01

    Objective To investigate in vitro adipocyte differentiation in baboon fetuses in response to reduced maternal nutrition. Design Cross-sectional comparison of adipocyte differentiation in normally grown fetuses and fetuses of pregnant baboons fed 70% control global diet from 30 days of pregnancy to term. Subjects Control (CTR) fetuses of ad libitum fed mothers (5 females and 5 males) and fetuses of mothers fed the 70% global diet eaten by CTR (MNR, 5 females and 5 males). The expression of gen...

  15. Hunting, food subsidies, and mesopredator release: the dynamics of crop-raiding baboons in a managed landscape

    OpenAIRE

    Taylor, RA; Ryan, SJ; Brashares, JS; Johnson, LR

    2016-01-01

    The establishment of protected areas or parks has become an important tool for wildlife conservation. However, frequent occurrences of human-wildlife conflict at the edges of these parks can undermine their conservation goals. Many African protected areas have experienced concurrent declines of apex predators alongside increases in both baboon abundance and the density of humans living near the park boundary. Baboons then take excursions outside of the park to raid crops for food, conflicting...

  16. Cortisol responses to immobilization with Telazol or ketamine in baboons (Papio cynocephalus/anubis) and rhesus macaques (Macaca mulatta)

    OpenAIRE

    Bentson, K L; Capitanio, J P; Mendoza, S P

    2003-01-01

    Little is known about the influence of Telazol on cortisol or of anesthetic agents on immunological measures, and reports of ketamine's effect on cortisol are inconsistent. We measured effects of Telazol, ketamine and blood sampling on cortisol in male rhesus macaques and male savannah baboons. We also obtained leukocyte counts in the macaques. In macaques, Telazol reduced cortisol in the morning but not in the afternoon; ketamine had no effect on cortisol in these animals. In baboons, cortis...

  17. 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...

  18. Studies on the propagation in cell culture and the infectivity for baboons of human hepatitis A virus

    International Nuclear Information System (INIS)

    Current aspects of hepatitis A and hepatitis A virus (HAV) research and the techniques used for the propagation and monitoring of HAV and HAV antigen (HA Ag) production in vitro and HAV infection in vivo, and its sequelae are reviewed. Radioimmunoassay, immunofluorescence and electron microscopic techniques for the demonstration of HA Ag were adapted for this investigation. The cell-adapted strain of HAV(MBB) was successfully propagated in the human hepatoma cell line PLC/PRF/5 at 32 degrees Celsius. A crystalline structure was demonstrated in the cytoplasm of HAV-infected cells by thin-section electron microscopy. The origin and significance of this structure is uncertain. A possible temperature variant of HAV (strain MBB) or an HAV-related baboon virus was detected in PLC/PRF/5 cells maintained at 37 degrees Celsius after infection with a faecal extract prepared from baboons which had been infected with the cell-cultured HAV. Baboons, both free-ranging and in captivity, were found to have antibodies to HAV, which suggests susceptibility to human HAV or another cross-reacting virus. The experimental infection of the Cape baboon orally, intravenously or by both routes with HAV were investigated. The results of the study suggest reasons for the presence of anti-HAV antibodies in certain baboon populations and show that the baboon is not an ideal model for hepatitis A investigations

  19. 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...

  20. 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...

  1. 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...

  2. 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

  3. 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.

  4. 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

  5. Metabolism and gastrointestinal absorption of neptunium and protactinium in adult baboons

    Energy Technology Data Exchange (ETDEWEB)

    Ralston, L.G.; Cohen, N.; Bhattacharyya, M.H.; Larsen, R.P.; Ayres, L.; Oldham, R.D.; Moretti, E.S.

    1985-01-01

    The metabolism of neptunium and protactinium was studied in adult female baboons following intravenous injection and intragastric intubation. Immediately following intravenous injection (10/sup -1/ to 10/sup -10/ mg Np per kg body wt), neptunium cleared rapidly from blood, deposited primarily in the skeleton (54 +- 5%) and liver (3 +- 0.2%), and was excreted predominantly via urine (40 +- 3%). For the first year post injection, neptunium was retained with a biological half-time of approx.100 days in liver and 1.5 +- 0.2 yr in bone. In comparison, injected protactinium (10/sup -9/ mg/kg) was retained in blood in higher concentrations and was initially eliminated in urine to a lesser extent (6 +- 3%). In vivo measurements indicated that protactinium was retained in bone (65 +- 0.3%) with a half-time of 3.5 +- 0.6 yr. Differences in the physicochemical states of the neptunium or protactinium solutions injected did not alter the metabolic behavior of these nuclides. The gastrointestinal absorption value for neptunium in two fasted baboons, sacrificed at 1 day post administration, was determined to be 0.92 +- 0.04%. Of the total amount of neptunium absorbed, 52 +- 3% was retained in bone, 6 +- 2% was in liver, and 42 +- 0.1% was excreted in urine. A method was developed to estimate GI absorption values for both nuclides in baboons which were not sacrificed. Absorption values calculated by this method for neptunium and protactinium in fasted baboons were 1.8 +- 0.8% and 0.65 +- 0.01%, respectively. Values for fed animals were 1 to 2 orders of magnitude less than those for fasted animals. 14 refs., 3 figs., 4 tabs. (DT)

  6. Curium-243,4 in the tissues of the adult baboon

    International Nuclear Information System (INIS)

    The curium content of the soft tissues and skeletons of six baboons (serially sacrificed at 3, 7, and 26 months post exposure) was determined in order to define the changing distribution of 2434Cm with time post intravenous injection. The efficacy of a DTPA treatment regimen was also investigated as a function of time of initiation of decorporation post injection of curium. Administration of DTPA treatment was begun at either 0.6, 1.5, or 8 months post exposure

  7. Contagious yawning in gelada baboons as a possible expression of empathy

    OpenAIRE

    Palagi, E.; Leone, A.; Mancini, G; Ferrari, P. F.

    2009-01-01

    Yawn contagion in humans has been proposed to be related to our capacity for empathy. It is presently unclear whether this capacity is uniquely human or shared with other primates, especially monkeys. Here, we show that in gelada baboons (Theropithecus gelada) yawning is contagious between individuals, especially those that are socially close, i.e., the contagiousness of yawning correlated with the level of grooming contact between individuals. This correlation persisted after controlling for...

  8. Variation in the nasal cavity of baboon hybrids with implications for late Pleistocene hominins.

    Science.gov (United States)

    Eichel, Kaleigh Anne; Ackermann, Rebecca Rogers

    2016-05-01

    Hybridization is increasingly proving to be an important force shaping human evolution. Comparisons of both ancient and modern genomes have provided support for a complex evolutionary scenario over the past million years, with evidence for multiple incidents of gene exchange. However, to date, genetic evidence is still limited in its ability to pinpoint the precise time and place of ancient admixture. For that we must rely on evidence of admixture from the skeleton. The research presented here builds on previous work on the crania of baboon hybrids, focusing on the nasal cavity of olive baboons, yellow baboons, and first generation (F1) hybrids. The nasal cavity is a particularly important anatomical region for study, given the clear differentiation of this feature in Neanderthals relative to their contemporaries, and therefore it is a feature that will likely differ in a distinctive manner in hybrids of these taxa. Metric data consist of 45 linear, area, and volume measurements taken from CT scans of known-pedigree baboon crania. Results indicate that there is clear evidence for differences among the nasal cavities of the parental taxa and their F1 hybrids, including a greater degree of sexual dimorphism in the hybrids. There is also some evidence for transgressive phenotypes in individual F1 animals. The greatest amount of shape variation occurs in the anterior bony cavity, the choana, and the mid-nasopharynx. Extrapolating our results to the fossil record, we would expect F1 hybrid fossils to have larger nasal cavities, on average, than either parental taxon, with overall nasal cavity shape showing the most profound changes in regions that are distinct between the parental taxa (e.g., anterior nasal cavity). We also expect size and shape differences to be more pronounced in male F1 hybrids than in females. Because of pronounced anterior nasal cavity differences between Neanderthals and their contemporaries, we suggest that this model might be effective for

  9. High Prevalence of Antibodies against the Bacterium Treponema pallidum in Senegalese Guinea Baboons (Papio papio)

    OpenAIRE

    Knauf, Sascha; Barnett, Ulrike; Maciej, Peter; Klapproth, Matthias; Ndao, Ibrahima; Frischmann, Sieghard; Fischer, Julia; Zinner, Dietmar; Liu, Hsi

    2015-01-01

    The bacterium Treponema pallidum is known to cause syphilis (ssp. pallidum), yaws (ssp. pertenue), and endemic syphilis (ssp. endemicum) in humans. Nonhuman primates have also been reported to be infected with the bacterium with equally versatile clinical manifestations, from severe skin ulcerations to asymptomatic. At present all simian strains are closely related to human yaws-causing strains, an important consideration for yaws eradication. We tested clinically healthy Guinea baboons (Papi...

  10. Microsomal drug-metabolizing enzymes in the olive baboon (papio anabis)

    DEFF Research Database (Denmark)

    1975-01-01

    1.1. The activity of microsomal drug-metabolizing enzymes—azo reductase, nitroreductase, p-hydroxylation, N-demethylation, O-demethylation, NADPH cytochrome c reductase and cytochrome P P-450—in the olive baboon are lower than in other animal species, e.g. mouse, rat, guinea-pig. 2. 2. The level is...... beta-glucuronidase is present more in the lysosomal than in the microsomal fraction....

  11. Biodistribution and radiation dosimetry of [11C]DASB in baboons

    International Nuclear Information System (INIS)

    Objective: The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [11C]DASB ([11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [11C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry. Methods: Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183±5 MBq/2.3±1.0 nmol of [11C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units. Results: Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6x10-2 mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies. Conclusion: Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [11C]DASB. In the United States, the absorbed dose to the lungs would limit [11C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female

  12. Consumption of palatable food decreases the anorectic effects of serotonergic, but not dopaminergic drugs in baboons

    OpenAIRE

    Foltin, Richard W.

    2011-01-01

    We examined the effects of periodic access to a palatable, high sugar content food (candy) in 8 male baboons on the anorectic response to d-amphetamine, which increases dopamine, and dexfenfluramine, which increases serotonin. During candy access, up to 200 candies containing 75% of energy as sugar were available during the morning on Mondays, Wednesdays and Fridays; food pellets (19% of energy as sugar) were available in the afternoon and throughout the remaining days of the week. During can...

  13. Resource base influences genome-wide DNA methylation levels in wild baboons (Papio cynocephalus).

    Science.gov (United States)

    Lea, Amanda J; Altmann, Jeanne; Alberts, Susan C; Tung, Jenny

    2016-04-01

    Variation in resource availability commonly exerts strong effects on fitness-related traits in wild animals. However, we know little about the molecular mechanisms that mediate these effects, or about their persistence over time. To address these questions, we profiled genome-wide whole-blood DNA methylation levels in two sets of wild baboons: (i) 'wild-feeding' baboons that foraged naturally in a savanna environment and (ii) 'Lodge' baboons that had ready access to spatially concentrated human food scraps, resulting in high feeding efficiency and low daily travel distances. We identified 1014 sites (0.20% of sites tested) that were differentially methylated between wild-feeding and Lodge baboons, providing the first evidence that resource availability shapes the epigenome in a wild mammal. Differentially methylated sites tended to occur in contiguous stretches (i.e., in differentially methylated regions or DMRs), in promoters and enhancers, and near metabolism-related genes, supporting their functional importance in gene regulation. In agreement, reporter assay experiments confirmed that methylation at the largest identified DMR, located in the promoter of a key glycolysis-related gene, was sufficient to causally drive changes in gene expression. Intriguingly, all dispersing males carried a consistent epigenetic signature of their membership in a wild-feeding group, regardless of whether males dispersed into or out of this group as adults. Together, our findings support a role for DNA methylation in mediating ecological effects on phenotypic traits in the wild and emphasize the dynamic environmental sensitivity of DNA methylation levels across the life course. PMID:26508127

  14. Chimpanzees empathize with group mates and humans, but not with baboons or unfamiliar chimpanzees

    OpenAIRE

    Campbell, Matthew W.; de Waal, Frans B. M.

    2014-01-01

    Human empathy can extend to strangers and even other species, but it is unknown whether non-humans are similarly broad in their empathic responses. We explored the breadth and flexibility of empathy in chimpanzees, a close relative of humans. We used contagious yawning to measure involuntary empathy and showed chimpanzees videos of familiar humans, unfamiliar humans and gelada baboons (an unfamiliar species). We tested whether each class of stimuli elicited contagion by comparing the effect o...

  15. Influence of Age, Reproductive Cycling Status, and Menstruation on the Vaginal Microbiome in Baboons (Papio anubis)

    OpenAIRE

    UCHIHASHI, M.; BERGIN, I. L.; BASSIS, C. M.; HASHWAY, S. A.; Chai, D.; Bell, J. D.

    2015-01-01

    The vaginal microbiome is believed to influence host health by providing protection from pathogens and influencing reproductive outcomes such as fertility and gestational length. In humans, age-associated declines in diversity of the vaginal microbiome occur in puberty and persist into adulthood. Additionally, menstruation has been associated with decreased microbial community stability. Adult female baboons, like other non-human primates (NHPs), have a different and highly diverse vaginal mi...

  16. Sex-Dependent Cognitive Performance in Baboon Offspring Following Maternal Caloric Restriction in Pregnancy and Lactation

    OpenAIRE

    RODRIGUEZ, Jesse S.; Bartlett, Thad Q; Keenan, Kathryn E.; Nathanielsz, Peter W.; Nijland, Mark J.

    2012-01-01

    In humans a suboptimal diet during development has negative outcomes in offspring. We investigated the behavioral outcomes in baboons born to mothers undergoing moderate maternal nutrient restriction (MNR). Maternal nutrient restriction mothers (n = 7) were fed 70% of food eaten by controls (CTR, n = 12) fed ad libitum throughout gestation and lactation. At 3.3 ± 0.2 (mean ± standard error of the mean [SEM]) years of age offspring (controls: female [FC, n = 8], male [MC, n = 4]; nutrient rest...

  17. Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

    Directory of Open Access Journals (Sweden)

    James N Mubiru

    Full Text Available The function of prostate-specific antigen (PSA is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes, cynomolgus monkeys (Macaca fascicularis, baboons (Papio hamadryas anubis, and African green monkeys (Chlorocebus aethiops. Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203.

  18. Treponema pallidum infection in the wild baboons of East Africa: distribution and genetic characterization of the strains responsible.

    Directory of Open Access Journals (Sweden)

    Kristin N Harper

    Full Text Available It has been known for decades that wild baboons are naturally infected with Treponema pallidum, the bacterium that causes the diseases syphilis (subsp. pallidum, yaws (subsp. pertenue, and bejel (subsp. endemicum in humans. Recently, a form of T. pallidum infection associated with severe genital lesions has been described in wild baboons at Lake Manyara National Park in Tanzania. In this study, we investigated ten additional sites in Tanzania and Kenya using a combination of macroscopic observation and serology, in order to determine whether the infection was present in each area. In addition, we obtained genetic sequence data from six polymorphic regions using T. pallidum strains collected from baboons at two different Tanzanian sites. We report that lesions consistent with T. pallidum infection were present at four of the five Tanzanian sites examined, and serology was used to confirm treponemal infection at three of these. By contrast, no signs of treponemal infection were observed at the six Kenyan sites, and serology indicated T. pallidum was present at only one of them. A survey of sexually mature baboons at Lake Manyara National Park in 2006 carried out as part of this study indicated that roughly ten percent displayed T. pallidum-associated lesions severe enough to cause major structural damage to the genitalia. Finally, we found that T. pallidum strains from Lake Manyara National Park and Serengeti National Park were genetically distinct, and a phylogeny suggested that baboon strains may have diverged prior to the clade containing human strains. We conclude that T. pallidum infection associated with genital lesions appears to be common in the wild baboons of the regions studied in Tanzania. Further study is needed to elucidate the infection's transmission mode, its associated morbidity and mortality, and the relationship between baboon and human strains.

  19. Treponema pallidum infection in the wild baboons of East Africa: distribution and genetic characterization of the strains responsible.

    Science.gov (United States)

    Harper, Kristin N; Fyumagwa, Robert D; Hoare, Richard; Wambura, Philemon N; Coppenhaver, Dorian H; Sapolsky, Robert M; Alberts, Susan C; Tung, Jenny; Rogers, Jeffrey; Kilewo, Morris; Batamuzi, Emmanuel K; Leendertz, Fabian H; Armelagos, George J; Knauf, Sascha

    2012-01-01

    It has been known for decades that wild baboons are naturally infected with Treponema pallidum, the bacterium that causes the diseases syphilis (subsp. pallidum), yaws (subsp. pertenue), and bejel (subsp. endemicum) in humans. Recently, a form of T. pallidum infection associated with severe genital lesions has been described in wild baboons at Lake Manyara National Park in Tanzania. In this study, we investigated ten additional sites in Tanzania and Kenya using a combination of macroscopic observation and serology, in order to determine whether the infection was present in each area. In addition, we obtained genetic sequence data from six polymorphic regions using T. pallidum strains collected from baboons at two different Tanzanian sites. We report that lesions consistent with T. pallidum infection were present at four of the five Tanzanian sites examined, and serology was used to confirm treponemal infection at three of these. By contrast, no signs of treponemal infection were observed at the six Kenyan sites, and serology indicated T. pallidum was present at only one of them. A survey of sexually mature baboons at Lake Manyara National Park in 2006 carried out as part of this study indicated that roughly ten percent displayed T. pallidum-associated lesions severe enough to cause major structural damage to the genitalia. Finally, we found that T. pallidum strains from Lake Manyara National Park and Serengeti National Park were genetically distinct, and a phylogeny suggested that baboon strains may have diverged prior to the clade containing human strains. We conclude that T. pallidum infection associated with genital lesions appears to be common in the wild baboons of the regions studied in Tanzania. Further study is needed to elucidate the infection's transmission mode, its associated morbidity and mortality, and the relationship between baboon and human strains. PMID:23284649

  20. Treponema pallidum Infection in the Wild Baboons of East Africa: Distribution and Genetic Characterization of the Strains Responsible

    Science.gov (United States)

    Harper, Kristin N.; Fyumagwa, Robert D.; Hoare, Richard; Wambura, Philemon N.; Coppenhaver, Dorian H.; Sapolsky, Robert M.; Alberts, Susan C.; Tung, Jenny; Rogers, Jeffrey; Kilewo, Morris; Batamuzi, Emmanuel K.; Leendertz, Fabian H.; Armelagos, George J.; Knauf, Sascha

    2012-01-01

    It has been known for decades that wild baboons are naturally infected with Treponema pallidum, the bacterium that causes the diseases syphilis (subsp. pallidum), yaws (subsp. pertenue), and bejel (subsp. endemicum) in humans. Recently, a form of T. pallidum infection associated with severe genital lesions has been described in wild baboons at Lake Manyara National Park in Tanzania. In this study, we investigated ten additional sites in Tanzania and Kenya using a combination of macroscopic observation and serology, in order to determine whether the infection was present in each area. In addition, we obtained genetic sequence data from six polymorphic regions using T. pallidum strains collected from baboons at two different Tanzanian sites. We report that lesions consistent with T. pallidum infection were present at four of the five Tanzanian sites examined, and serology was used to confirm treponemal infection at three of these. By contrast, no signs of treponemal infection were observed at the six Kenyan sites, and serology indicated T. pallidum was present at only one of them. A survey of sexually mature baboons at Lake Manyara National Park in 2006 carried out as part of this study indicated that roughly ten percent displayed T. pallidum-associated lesions severe enough to cause major structural damage to the genitalia. Finally, we found that T. pallidum strains from Lake Manyara National Park and Serengeti National Park were genetically distinct, and a phylogeny suggested that baboon strains may have diverged prior to the clade containing human strains. We conclude that T. pallidum infection associated with genital lesions appears to be common in the wild baboons of the regions studied in Tanzania. Further study is needed to elucidate the infection's transmission mode, its associated morbidity and mortality, and the relationship between baboon and human strains. PMID:23284649

  1. Glutamine Modulates Macrophage Lipotoxicity

    Directory of Open Access Journals (Sweden)

    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.

  2. Perawatan Ortodontik Gigi Anterior Berjejal dengan Tulang Alveolar yang Tipis

    Directory of Open Access Journals (Sweden)

    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.

  3. Orthopantomographic study of the alveolar bone level on periodontal disease

    International Nuclear Information System (INIS)

    The author had measured the alveolar bone level of periodontal disease on 50 cases of orthopantomogram to detect the degree of alveolar bone resorption of both sexes of Korean. The results were obtained as follows; 1. Alveolar bone resorption of mesial and distal portion was similar in same patient. 2. The order of alveolar bone resorption was mandibular anterior region, posterior region, canine and premolar region of both jaws. 3. The degree of alveolar bone destruction was severe in shorter root length than longer one. 4. The degree of alveolar bone resorption was severe in fourth decades.

  4. 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...

  5. 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

  6. 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...

  7. The Salmonella virulence plasmid enhances Salmonella-induced lysis of macrophages and influences inflammatory responses.

    OpenAIRE

    Guilloteau, L. A.; Wallis, T S; A.V. Gautier; Macintyre, S.; Platt, D. J.; Lax, A J

    1996-01-01

    The Salmonella dublin virulence plasmid mediates systemic infection in mice and cattle. Here, we analyze the interaction between wild-type and plasmid-cured Salmonella strains with phagocytes in vitro and in vivo. The intracellular recovery of S. dublin from murine peritoneal and bovine alveolar macrophages cultured in the presence of gentamicin in vitro was not related to virulence plasmid carriage. However, the virulence plasmid increased the lytic activity of S. dublin, Salmonella typhimur...

  8. 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...

  9. 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...

  10. 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...

  11. Alveolar rhabdomyosarcoma in children with histomorphological review

    Directory of Open Access Journals (Sweden)

    S. K. Nema

    2014-04-01

    Full Text Available Rhabdomyosarcomas (RMS are aggressive malignant neoplasm of mesenchymal origin, related to skeletal muscle lineage. These are the most common soft tissue tumors in children. The diagnosis is made by microscopic analysis and ancillary techniques like immunohistochemistry, electron microscopy, cytogenetics and molecular biology. We encountered a case of a 03 years old child who presented with a tender, reddish, soft swelling over cheek for three weeks. The FNAC was reported as a small round cell tumor, Probably Primitive Neuroectodermal Tumor (PNET. The biopsy of tumor revealed a small round cell tumor with an alveolar pattern. Tumor giant cells were absent and mitotic figures were infrequent. Hence, differentials of alveolar rhabdomyosarcoma and PNET were rendered. Immunohistochemistry (IHC demonstrated desmin positivity. Thus, a final diagnosis of alveolar rhabdomyosarcoma was offered. [Int J Res Med Sci 2014; 2(2.000: 775-778

  12. 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.

  13. 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

  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. 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.

  16. Adenosine regulation of alveolar fluid clearance

    OpenAIRE

    Factor, Phillip; Mutlu, Göskhan M.; Chen, Lan; Mohameed, Jameel; Akhmedov, Alexander T.; Meng, Fan Jing; Jilling, Tamas; Lewis, Erin Rachel; Johnson, Meshell D.; Xu, Anna; Kass, Daniel; Martino, Janice M.; Bellmeyer, Amy; Albazi, John S.; Emala, Charles

    2007-01-01

    Adenosine is a purine nucleoside that regulates cell function through G protein-coupled receptors that activate or inhibit adenylyl cyclase. Based on the understanding that cAMP regulates alveolar epithelial active Na+ transport, we hypothesized that adenosine and its receptors have the potential to regulate alveolar ion transport and airspace fluid content. Herein, we report that type 1 (A1R), 2a (A2aR), 2b (A2bR), and 3 (A3R) adenosine receptors are present in rat and mouse lungs and alveol...

  17. 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.

  18. 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...... injuries associated with third molar surgery, other dento-alveolar surgery or implant surgery occur sufficiently often to render prevention a key issue....... assessing tactile, thermal, and positional perception as well as two-point discrimination and pain. In 48 patients with IAN injuries of differing etiologies who did not undergo surgery, 32 patients with injury associated with third molar surgery exhibited significant spontaneous improvement of sensory...

  19. Bone Marrow Mesenchymal Stem Cells Inhibit Lipopolysaccharide-Induced Inflammatory Reactions in Macrophages and Endothelial Cells

    Directory of Open Access Journals (Sweden)

    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.

  20. 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...

  1. Inter- and intrahabitat dietary variability of chacma baboons (Papio ursinus) in South African savannas based on fecal delta13C, delta15N, and %N.

    Science.gov (United States)

    Codron, Daryl; Lee-Thorp, Julia A; Sponheimer, Matt; de Ruiter, Darryl; Codron, Jacqueline

    2006-02-01

    Baboons are dietary generalists, consuming a wide range of food items in varying proportions. It is thus difficult to quantify and explain the dietary behavior of these primates. We present stable carbon (delta(13)C) and nitrogen (delta(15)N) isotopic data, and percentage nitrogen (%N), of feces from chacma baboons (Papio ursinus) living in two savanna environments of South Africa: the mountainous Waterberg region and the low-lying Kruger National Park. Baboons living in the more homogeneous landscapes of the Waterberg consume a more isotopically heterogeneous diet than their counterparts living in Kruger Park. Grasses and other C(4)-based foods comprise between approximately 10-20% (on average) of the bulk diet of Kruger Park baboons. Carbon isotopic data from the Waterberg suggest diets of approximately 30-50% grass, which is higher than generally reported for baboons across the African savanna. Based on observations of succulent-feeding, we propose that baboons in the Waterberg consume a mix of C(4) grasses and CAM-photosynthesizing succulents in combined proportions varying between approximately 5-75% (average, approximately 35%). Fecal delta(15)N of baboons is lower than that of sympatric ungulates, which may be due to a combination of low levels of faunivory, foraging on subterranean plant parts, or the use of human foods in the case of Kruger Park populations. Fecal N levels in baboons are consistently higher than those of sympatric ungulate herbivores, indicating that baboons consume a greater proportion of protein-rich foods than do other savanna mammals. These data suggest that chacma baboons adapt their dietary behavior so as to maximize protein intake, regardless of their environment. PMID:16247809

  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. 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

  4. 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

  5. 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

  6. Complement inhibition decreases early fibrogenic events in the lung of septic baboons.

    Science.gov (United States)

    Silasi-Mansat, Robert; Zhu, Hua; Georgescu, Constantin; Popescu, Narcis; Keshari, Ravi S; Peer, Glenn; Lupu, Cristina; Taylor, Fletcher B; Pereira, Heloise Anne; Kinasewitz, Gary; Lambris, John D; Lupu, Florea

    2015-11-01

    Acute respiratory distress syndrome (ARDS) induced by severe sepsis can trigger persistent inflammation and fibrosis. We have shown that experimental sepsis in baboons recapitulates ARDS progression in humans, including chronic inflammation and long-lasting fibrosis in the lung. Complement activation products may contribute to the fibroproliferative response, suggesting that complement inhibitors are potential therapeutic agents. We have been suggested that treatment of septic baboons with compstatin, a C3 convertase inhibitor protects against ARDS-induced fibroproliferation. Baboons challenged with 10(9) cfu/kg (LD50) live E. coli by intravenous infusion were treated or not with compstatin at the time of challenge or 5 hrs thereafter. Changes in the fibroproliferative response at 24 hrs post-challenge were analysed at both transcript and protein levels. Gene expression analysis showed that sepsis induced fibrotic responses in the lung as early as 24 hrs post-bacterial challenge. Immunochemical and biochemical analysis revealed enhanced collagen synthesis, induction of profibrotic factors and increased cell recruitment and proliferation. Specific inhibition of complement with compstatin down-regulated sepsis-induced fibrosis genes, including transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), tissue inhibitor of metalloproteinase 1 (TIMP1), various collagens and chemokines responsible for fibrocyte recruitment (e.g. chemokine (C-C motif) ligand 2 (CCL2) and 12 (CCL12)). Compstatin decreased the accumulation of myofibroblasts and proliferating cells, reduced the production of fibrosis mediators (TGF-β, phospho-Smad-2 and CTGF) and inhibited collagen deposition. Our data demonstrate that complement inhibition effectively attenuates collagen deposition and fibrotic responses in the lung after severe sepsis. Inhibiting complement could prove an attractive strategy for preventing sepsis-induced fibrosis of the lung. PMID:26337158

  7. Dynamic testing of old and young baboon cortical bone with numerical validation

    Science.gov (United States)

    Chocron, S.; Nicolella, D.; Nicholls, A. E.; Bredbenner, T.; Havill, L.

    2012-08-01

    Cortical bone tensile mechanical properties at quasistatic and high rates (˜300s-1) were determined ex vivo using the right femurs of 12 female baboons, (Papio hamadryas spp.) from the Texas Biomedical Research Institute/Southwest National Primate Research Center in San Antonio, Texas. The animals were divided into two age groups: a young age group (6.63 ± 0.6 years) and an old age group (26.96 ± 1.3 years). Seven specimens per group were monotonically loaded to failure to determine their mechanical properties. The quasistatic strength of the bone for the old group was just a little (but not significantly) lower than the young group. High strain rate tests performed with the Hopkinson bar indicate that baboon bone from the older group was significantly weaker under impact loads than that from the younger group. This observation is particularly important due to the similarities between baboon and human bone tissue. Typical strain rates for these tests ranged from 130s-1 to 250s-1. A full-size 3-D simulation of the Hopkinson bar test was performed to confirm that the bone specimen was under stress equilibrium and to evaluate the consistency of the modulus and strength inferred from the tests. Simulations were performed in which the modulus, strength and failure strain were varied to see the sensitivity of the results. Additionally, simplified simulations were performed to estimate the strain rate environment of a femur during a fall at an impact velocity of 5 m/s, similar to a free fall velocity from a height of 1.3 meters. The simulations confirm that strain rates obtained in the Hopkinson bar are relevant because they are similar to those expected inr such a fall.

  8. 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.

  9. Barrier and uptake mechanisms in the cerebrovascular response to noradrenaline. [/sup 133/Xe tracer technique, baboons

    Energy Technology Data Exchange (ETDEWEB)

    McCalden, T.A.; Eidelman, B.H.; Mendelow, A.D.

    1977-10-01

    Cerebral blood flow (CBF) was measured in 20 baboons by the intra-arterial xenon-133 injection method. The CBF responses to intra-arterial infusions of noradrenaline (NA) were determined. These responses were normally found to be vasodilator and mediated by beta adrenoreceptors. After infusion of substances blocking extraneuronal uptake of NA or opening of the blood-brain barrier, this vasodilation was either abolished or converted to an alpha-receptor mediated vasoconstriction. This suggests that normally the cerebral circulation is protected against noradrenergic vasoconstriction by mechanisms reducing the concentration of NA in the tunica media to below threshold for alpha-adrenoreceptor stimulation.

  10. Biodistribution and radiation dosimetry of [{sup 11}C]DASB in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Belanger, Marie-Jose [Department of Psychiatry, Columbia University College of Physicians and Surgeons New York, NY 10032 (United States); Division of Brain Imaging, Department of Neuroscience, New York State Pyschiatric Institute, New York, NY 10032 (United States); Simpson, Norman R. [Department of Radiology, Columbia University College of Physicians and Surgeons and Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Wang, Theodore [Department of Radiology, Columbia University College of Physicians and Surgeons and Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032 (United States); Division of Brain Imaging, Department of Neuroscience, New York State Pyschiatric Institute, New York, NY 10032 (United States)] [and others

    2004-11-01

    Objective: The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [{sup 11}C]DASB ([{sup 11}C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [{sup 11}C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry. Methods: Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183{+-}5 MBq/2.3{+-}1.0 nmol of [{sup 11}C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units. Results: Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6x10{sup -2} mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies. Conclusion: Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [{sup 11}C]DASB. In the United States, the absorbed dose to the lungs would limit [{sup 11}C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female.

  11. Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model

    International Nuclear Information System (INIS)

    Bone-seeking radiopharmaceuticals such as ethylenediaminetetramethylene phosphonate (EDTMP) complexes of samarium-153 and holmium-166 are receiving considerable attention for therapeutic treatment of bone metastases. In this study, using the baboon experimental model, multicompartmental analysis revealed that with regard to pharmacokinetics, biodistribution, and skeletal localisation, 166Ho-EDTMP was significantly inferior to 153Sm-EDTMP and 99mTc-MDP. A more suitable 166Ho-bone-seeking agent should thus be sought for closer similarity to 153Sm-EDTMP to exploit fully the therapeutic potential of its shorter half-life and more energetic beta radiation

  12. Baboon alcohol dehydrogenase isozymes: phenotypic changes in liver following chronic consumption of alcohol.

    Science.gov (United States)

    Holmes, R S; VandeBerg, J L

    1987-01-01

    According to the nomenclature of Vallee and Bazzone [1983] for mammalian alcohol dehydrogenase (ADH) isozymes, baboon ADHs comprise three major classes of activity, which were distinguished according to the following properties: Class I ADHs. These isozymes exhibited low-Km characteristics with ethanol as substrate, high isoelectric points (8.5-9.3), and sensitivity to 5 mM 4-methyl pyrazole inhibition, and were the major liver (ADH-2) and kidney (ADH-1) isozymes in the baboon. Class II ADHs. These isozymes showed high-Km values for ethanol, neutral isoelectric points (7.7 for the liver ADH-4 [pi-ADH] and 7.2 for the major stomach ADH [ADH-3], respectively), and were insensitive to inhibition with 5 mM 4-methyl pyrazole. Class III ADH. This enzyme was characterized by its inactivity with ethanol as substrate (up to 0.5 M), insensitivity to 4-methyl pyrazole inhibition, preference for medium-chain-length alcohols as substrate (trans-2-hexen-1-ol was routinely used in this study), and an isoelectric point (6.5) similar to that of the human liver chi-ADH (pI 6.4). Major activity variation of the liver pi-ADH (ADH-4) isozyme was observed among the 114 liver samples examined, with 34 percent exhibiting a null (or low-activity) phenotype. An electrophoretic variant phenotype for the major class II stomach isozyme (ADH-3) was also found in the population studied. The baboon was used as a model for studying alcohol-induced changes in liver ADH phenotype following chronic alcohol consumption. Prepuberal male baboons were pair-fed nutritionally adequate liquid diets containing ethanol (50 percent of calories) or isocaloric carbohydrates, and liver ADH isozyme patterns from biopsy samples were monitored for 20 weeks. Dramatic decreases in class II liver ADH activity (ADH-4, or pi-ADH) were observed within 4 weeks after the start of alcohol feeding, and a shift in liver class I isozymes was found during the later stages of alcohol consumption. These changes during chronic

  13. [Apoptosis of alveolar lymphocytes in sarcoidosis and in control group is more frequent in smokers than in nonsmoking persons].

    Science.gov (United States)

    Kopiński, Piotr; Przybylsk, Grzegorz; Balicka-Slusarczyk, Barbara; Jarzemska, Agnieszka; Dyczek, Andrzej; Pinis, Grazyna; Bartczak, Karina; Plato, Marta; Jankowski, Marek; Szczeklik, Jerzy

    2006-01-01

    Cigarette smoking enhances apoptosis rate of alveolar macrophages. However, little is known about the appearance and extension of apoptosis in bronchoalveolar lavage (BAL) lymphocytes originating from smoker individuals, both in pulmonary sarcoidosis (the disease characterized by lymphocytic alveolitis) and in controls. BAL was carried out in 60 nontreated patients with pulmonary sarcoidosis, subdivided acc. smoking status and in 22 control persons, free of any lung pathology. BAL (alveolar) lymphocytes were a) stained for TUNEL; b) permeabilized and stained with PI for late apoptosis/cell cycle analyses; c) immunophenotyped, including CD95, CD95 Ligand, Bcl-2, Bcl-XL, Bak and insulin-like growth factor-I (IGF-I) expression. BD FACSCalibure flow cytometer, PC Lysys and ModFit software were applied. The low number of AL entered apoptosis, which was confirmed by both techniques. Cigarette smokers were characterized by higher AL apoptosis percentage in respective subgroups (sarcoidosis: 0.6 +/- 0.13 in nonsmokers vs 0.9 +/- 0.23 in smokers; controls: 0.85 +/- 0.23 in nonsmokers vs 1.5 +/- 0.35 smokers, median +/- SEM, p < 0.05); the proliferation rate was lower. Decreased IGF-I expression in AL of sarcoidosis smokers was observed (13.5 +/- 9.2 vs 46.0 +/- 6.0 in nonsmokers, p < 0.05). No differences were found between studied groups in expression of Bcl-2, Fas and FasL molecules (except significantly declined ratio of CD8+FasL+ cells in sarcoidosis nonsmokers). AL apoptosis rate was positively correlated with respective alveolar macrophage results (Rs = +0.59, p < 0.00001) and negatively with CD4/CD8 ratio (Rs = -0.32, p < 0.001); no correlation was found with lung function test results and with Bcl-2, Fas and FasL expression in BAL cells. Apoptosis of alveolar lymphocytes was more frequent in nonsmokers both in pulmonary sarcoidosis and in controls; lower AL percentage proliferates. These phenomena seem to participate in lower AL percentage, observed in smoker

  14. Monkey Management: Using Spatial Ecology to Understand the Extent and Severity of Human-Baboon Conflict in the Cape Peninsula, South Africa

    Directory of Open Access Journals (Sweden)

    M Justin. O'Riain

    2012-09-01

    Full Text Available Conflict with humans poses one of the greatest threats to the persistence and survival of all wildlife. In the Cape Peninsula, South Africa, human-baboon conflict levels remain high despite substantial investment by conservation authorities in a variety of mitigation measures. Here we explore how spatial ecology can inform wildlife managers on the extent and severity of both current and projected human-baboon conflict. We apply conservative and generous densities--2.3 and 5.9 baboons/km2--to hypothetical landscape management scenarios to estimate whether the chacma baboon (Papio ursinus population in the Cape Peninsula is currently overabundant. We correlate conflict indices with spatial variables to explain intertroop differences in conflict levels. We investigate how an understanding of key elements of baboon ecology, including sleeping-site characteristics and intertroop territoriality, can direct management efforts and mitigate conflict. Our findings suggest that the current population of 475 baboons is below even the most conservative density estimate and that the area could potentially sustain up to 799 baboons. Conflict levels correlated positively with the loss of access to low-lying land through habitat transformation (Pearson r = 0.77, p = 0.015, n = 9 troops, and negatively with the distance of sleeping sites from the urban edge (Pearson r = 0.81, p = 0.001, n = 9 troops. Despite the availability of suitable sleeping sites elsewhere, more than half of all troops slept

  15. Comparison of common platelet receptors between the chacma baboon (Papio ursinus) and human for use in pre-clinical human-targeted anti-platelet studies.

    Science.gov (United States)

    Janse van Rensburg, Walter J

    2016-06-01

    Anti-platelet agents play a central part in the treatment and prevention of acute thrombotic events. Discriminating animal models are needed for the development of novel agents. The chacma baboon has been extensively used as a model to evaluate anti-platelet agents. However, limited data exist to prove the translatability of this species to humans. We aimed to determine the suitability of the chacma baboon in preclinical human targeted GPIIb/IIIa, GPIbα and P2Y12 studies. Light-transmission platelet aggregometry (LTA), whole blood impedance aggregometry, receptor number quantification and genomic DNA sequencing were performed. Baboon ADP and arachidonic acid-induced LTA aggregation results differed significantly from human values, even at increased concentrations. LTA ristocetin-induced agglutination was comparable between species, but baboon platelets needed twice the concentration of ristocetin to elicit a similar response. Citrated baboon blood had significantly less aggregation than humans when evaluated with impedance aggregometry. However, hirudinised baboon whole blood gave similar aggregation as humans at the same agonist concentrations. GPIIb, GPIIIa and GPIbα numbers were significantly more on the baboon platelets. None of the amino acids deemed vital for receptor function, ligand binding or receptor inhibition, were radically different between the species. However, a conservative change in a calcium-binding region of GPIIb may render the baboon platelets more sensitive to calcium-binding agents. The chacma baboon may be used for the evaluation of human-targeted GPIIb/IIIa-, GPIbα- and P2Y12-inhibiting agents. However, the best anticoagulant, optimal agonist concentrations, increase in receptor number and sequence differences must be considered for any future studies. PMID:26559117

  16. 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

  17. Short term kinetics of uranium in the adult baboon: preliminary data

    International Nuclear Information System (INIS)

    Two adult female Kenya baboons received single intravenous injections of monomeric 237U nitrate. The doses administered were 4.21 μCi 237U. The retention and distribution were followed in the two baboons at predetermined intervals post-injection. Retetion and distribution curves were plotted over the intervals from 3 to 44 days post-injection. Analysis of the head counting data revealed that after nine days post-injection the short-term clearance from the skull (bone) could be expressed by an exponential function with a mean half time of 55 days with individual t/sub 1/2/ values of 69.3 and 41.0 days. The short-term t/sub 1/2/ is apparently due to the initial ion exchange capabilities of the skeletal surface while the longer-term component represents uranium which has become incorporated into skeletal structures. In order to investigate the long-term component, a longer-lived isotope of uranium 233U was used. The whole body mean biological half-life of 237U was calculated to be 25.9 +- 8.8 days. The kidney measurements were fitted to a two exponential curve with mean half times of 6.8 +- 4.0 and 45.4 +- 18.8 days. The liver measurements were inconclusive probably due to the fact that uranium is not known to concentrate in the liver to any extent

  18. In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT

    International Nuclear Information System (INIS)

    To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[123I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[123I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (Vd ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal Vd was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in Vd or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment

  19. Cardiac output by Doppler echocardiography in the premature baboon: Comparison with radiolabeled microspheres

    International Nuclear Information System (INIS)

    Pulsed-Doppler echocardiography (PDE) is a useful noninvasive method for determining left ventricular output (LVO). However, despite increasingly widespread use in neonatal intensive care units, validation studies in prematures with cardiopulmonary disease are lacking. The purpose of this study was to compare radiolabeled microsphere (RLM) and PDE measurements of LVO, using the critically ill premature baboon as a model of the human neonate. Twenty-two paired RLM and PDE measurements of LVO were obtained in 14 animals between 3 and 24 h of age. Average PDE LVO was 152 ml/min/kg (range, 40-258 ml/min/kg) compared to 158 ml/min/kg (range, 67-278 ml/min/kg) measured by RLM. Linear regression analysis of the paired measurements showed good correlation with a slope near unity (gamma = 0.94x + 4.20, r = 0.91, SEE = 25.7 ml). The authors conclude that PDE determinations of LVO compare well with those measured by RLM in the premature baboon. PDE appears to provide a valid estimate of LVO and should be useful in human prematures with cardiopulmonary distress

  20. Chimpanzees empathize with group mates and humans, but not with baboons or unfamiliar chimpanzees.

    Science.gov (United States)

    Campbell, Matthew W; de Waal, Frans B M

    2014-05-01

    Human empathy can extend to strangers and even other species, but it is unknown whether non-humans are similarly broad in their empathic responses. We explored the breadth and flexibility of empathy in chimpanzees, a close relative of humans. We used contagious yawning to measure involuntary empathy and showed chimpanzees videos of familiar humans, unfamiliar humans and gelada baboons (an unfamiliar species). We tested whether each class of stimuli elicited contagion by comparing the effect of yawn and control videos. After including previous data on the response to ingroup and outgroup chimpanzees, we found that familiar and unfamiliar humans elicited contagion equal to that of ingroup chimpanzees. Gelada baboons did not elicit contagion, and the response to them was equal to that of outgroup chimpanzees. However, the chimpanzees watched the outgroup chimpanzee videos more than any other. The combination of high interest and low contagion may stem from hostility towards unfamiliar chimpanzees, which may interfere with an empathic response. Overall, chimpanzees showed flexibility in that they formed an empathic connection with a different species, including unknown members of that species. These results imply that human empathic flexibility is shared with related species. PMID:24619445