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Sample records for alveolar basal epithelial

  1. Claudins and alveolar epithelial barrier function in the lung

    OpenAIRE

    Frank, James A.

    2012-01-01

    The alveolar epithelium of the lung constitutes a unique interface with the outside environment. This thin barrier must maintain a surface for gas transfer while being continuously exposed to potentially hazardous environmental stimuli. Small differences in alveolar epithelial barrier properties could therefore have a large impact on disease susceptibility or outcome. Moreover, recent work has focused attention on the alveolar epithelium as central to several lung diseases, including acute lu...

  2. Alveolar epithelial type II cell: defender of the alveolus revisited

    OpenAIRE

    Fehrenbach Heinz

    2001-01-01

    Abstract In 1977, Mason and Williams developed the concept of the alveolar epithelial type II (AE2) cell as a defender of the alveolus. It is well known that AE2 cells synthesise, secrete, and recycle all components of the surfactant that regulates alveolar surface tension in mammalian lungs. AE2 cells influence extracellular surfactant transformation by regulating, for example, pH and [Ca2+] of the hypophase. AE2 cells play various roles in alveolar fluid balance, coagulation/fibrinolysis, a...

  3. Alveolar epithelial permeability in bronchial asthma in children

    International Nuclear Information System (INIS)

    To evaluate alveolar epithelial permeability (kep) in children with bronchial asthma, 99mTc-DTPA (diethylene triamine penta acetate) aerosol lung inhalation scintigraphies were performed. There was no correlation between the kep value and the severity of asthma. On the other hand, out of 10 cases which had no aerosol deposition defect in the lung field, 4 showed high kep values on the whole lung field and 7 had high kep value areas, particularly apparent in the upper lung field. These results suggest that even when the central airway lesions are mild, severe damage exists in the alveolar region of the peripheral airway. (author)

  4. 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...

  5. Oxidative Stress, Cell Death, and Other Damage to Alveolar Epithelial Cells Induced by Cigarette Smoke

    OpenAIRE

    Aoshiba K; Nagai A

    2003-01-01

    Abstract Cigarette smoking is a major risk factor in the development of various lung diseases, including pulmonary emphysema, pulmonary fibrosis, and lung cancer. The mechanisms of these diseases include alterations in alveolar epithelial cells, which are essential in the maintenance of normal alveolar architecture and function. Following cigarette smoking, alterations in alveolar epithelial cells induce an increase in epithelial permeability, a decrease in surfactant production, the inapprop...

  6. Dexmedetomidine Attenuates Bilirubin-Induced Lung Alveolar Epithelial Cell Death In Vitro and In Vivo*

    OpenAIRE

    Cui, Jian; Zhao, Hailin; Yi, Bin; Zeng, Jing; Lu, Kaizhi; Ma, Daqing

    2015-01-01

    Objective: To investigate bilirubin-induced lung alveolar epithelial cell injury together with the protection afforded by dexmedetomidine. Design: Prospective, randomized, controlled study. Setting: Research laboratory. Subjects: Sprague Dawley rats. Interventions: Alveolar epithelial A549 cell lines were cultured and received bilirubin (from 0 to 160 μM) to explore the protective pathway of dexmedetomidine on bilirubin-induced alveolar epithelial cell injury assessed by immunochemistry and f...

  7. Oxidative Stress, Cell Death, and Other Damage to Alveolar Epithelial Cells Induced by Cigarette Smoke

    Directory of Open Access Journals (Sweden)

    Nagai A

    2003-09-01

    Full Text Available Abstract Cigarette smoking is a major risk factor in the development of various lung diseases, including pulmonary emphysema, pulmonary fibrosis, and lung cancer. The mechanisms of these diseases include alterations in alveolar epithelial cells, which are essential in the maintenance of normal alveolar architecture and function. Following cigarette smoking, alterations in alveolar epithelial cells induce an increase in epithelial permeability, a decrease in surfactant production, the inappropriate production of inflammatory cytokines and growth factors, and an increased risk of lung cancer. However, the most deleterious effect of cigarette smoke on alveolar epithelial cells is cell death, i.e., either apoptosis or necrosis depending on the magnitude of cigarette smoke exposure. Cell death induced by cigarette smoke exposure can largely be accounted for by an enhancement in oxidative stress. In fact, cigarette smoke contains and generates many reactive oxygen species that damage alveolar epithelial cells. Whether apoptosis and/or necrosis in alveolar epithelial cells is enhanced in healthy cigarette smokers is presently unclear. However, recent evidence indicates that the apoptosis of alveolar epithelial cells and alveolar endothelial cells is involved in the pathogenesis of pulmonary emphysema, an important cigarette smoke-induced lung disease characterized by the loss of alveolar structures. This review will discuss oxidative stress, cell death, and other damage to alveolar epithelial cells induced by cigarette smoke.

  8. Alveolar epithelial type II cell: defender of the alveolus revisited

    Directory of Open Access Journals (Sweden)

    Fehrenbach Heinz

    2001-01-01

    Full Text Available Abstract In 1977, Mason and Williams developed the concept of the alveolar epithelial type II (AE2 cell as a defender of the alveolus. It is well known that AE2 cells synthesise, secrete, and recycle all components of the surfactant that regulates alveolar surface tension in mammalian lungs. AE2 cells influence extracellular surfactant transformation by regulating, for example, pH and [Ca2+] of the hypophase. AE2 cells play various roles in alveolar fluid balance, coagulation/fibrinolysis, and host defence. AE2 cells proliferate, differentiate into AE1 cells, and remove apoptotic AE2 cells by phagocytosis, thus contributing to epithelial repair. AE2 cells may act as immunoregulatory cells. AE2 cells interact with resident and mobile cells, either directly by membrane contact or indirectly via cytokines/growth factors and their receptors, thus representing an integrative unit within the alveolus. Although most data support the concept, the controversy about the character of hyperplastic AE2 cells, reported to synthesise profibrotic factors, proscribes drawing a definite conclusion today.

  9. Effects of elastase and cigarette smoke on alveolar epithelial permeability

    International Nuclear Information System (INIS)

    To determine whether instilled porcine pancreatic elastase (PPE) increases alveolar epithelial permeability, the authors measured alveolar epithelium permeability X surface area (PS) for [14C]sucrose and 125I-bovine serum albumin in isolated perfused lungs from hamsters previously exposed to PPE and/or cigarette smoke. Saline (0.5 ml) with 0, 5, or 20 units PPE was instilled intratracheally in anesthetized hamsters. Those exposed to smoke for 4-6 wk received 0 or 5 units; PS was measured 3 h later. Nonsmokers received 0, 5, or 20 units; PS was measured 3 h, 24 h, or 5 days later. Control PS values were (cm3/s X 10(-4), +/- SE) 0.84 +/- 0.11 for sucrose and 0.030 +/- 0.006 for BSA. Three and 24 h following 20 units PPE, (PS)sucrose was twice the control valve. (PS)BSA was four times control at 3 h but not significantly increased at 24 h. Five days after PPE both were back to control levels. Five units PPE or smoke exposure alone caused no PS changes. Smoke exposure and 5 units PPE caused (PS)sucrose to increase markedly (1.85 +/- 0.32); (PS)BSA was not significantly increased (0.076 +/- 0.026). Thus, instilled PPE causes reversible increases in alveolar epithelial PS; cigarette smoking potentiates this effect

  10. Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

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    Araki Hiromasa

    2007-04-01

    Full Text Available Abstract Background Proteinase-activated receptors (PARs; PAR1–4 that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells. Results Stimulation of PAR with thrombin (1 U/ml or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β. Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial

  11. Hemoglobin is Expressed in Alveolar Epithelial Type II Cells

    OpenAIRE

    Bhaskaran, Manoj; Chen, Haifeng; Chen, Zhongmong; Liu, Lin

    2005-01-01

    Hemoglobin is the main oxygen carrying heme protein in erythrocytes. In an effort to study the differential gene expression of alveolar epithelial type I and type II cells using DNA microarray technique, we found that the mRNAs of hemoglobin α- and β-chains were expressed in type II cells, but not in type I cells. The microarray data were confirmed by RT-PCR. The mRNA expression of both chains decreased when type II cells trans-differentiated into type I-like cells. Immunocyto/histochemistry ...

  12. The potential of microfluidic lung epithelial wounding: towards in vivo-like alveolar microinjuries

    OpenAIRE

    Felder, Marcel; Stucki, Andreas; Stucki, Janick; Geiser, Thomas; Guenat, Olivier Thierry

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) remains a major clinical challenge to date. Repeated alveolar epithelial microinjuries are considered as the starting point and the key event in both the development and the progression of IPF. Various pro-fibrotic agents have been identified and shown to cause alveolar damage. In IPF, however, no leading cause of alveolar epithelial microinjuries can be identified and the exact etiology remains elusive. New results from epidemiologic studies suggest a caus...

  13. A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells

    OpenAIRE

    Wang, Dachun; Haviland, David L.; Burns, Alan R.; Zsigmond, Eva; Wetsel, Rick A.

    2007-01-01

    Alveolar epithelial type II (ATII) cells are small, cuboidal cells that constitute ≈60% of the pulmonary alveolar epithelium. These cells are crucial for repair of the injured alveolus by differentiating into alveolar epithelial type I cells. ATII cells derived from human ES (hES) cells are a promising source of cells that could be used therapeutically to treat distal lung diseases. We have developed a reliable transfection and culture procedure, which facilitates, via genetic selection, the ...

  14. Biophysical determinants of alveolar epithelial plasma membrane wounding associated with mechanical ventilation

    OpenAIRE

    Hussein, Omar; Walters, Bruce; Stroetz, Randolph; Valencia, Paul; McCall, Deborah; Hubmayr, Rolf D.

    2013-01-01

    Mechanical ventilation may cause harm by straining lungs at a time they are particularly prone to injury from deforming stress. The objective of this study was to define the relative contributions of alveolar overdistension and cyclic recruitment and “collapse” of unstable lung units to membrane wounding of alveolar epithelial cells. We measured the interactive effects of tidal volume (VT), transpulmonary pressure (PTP), and of airspace liquid on the number of alveolar epithelial cells with p...

  15. Inhibitory effect of receptor for advanced glycation end products (RAGE) on the TGF-β-induced alveolar epithelial to mesenchymal transition

    OpenAIRE

    Song, Jeong Sup; Kang, Chun Mi; Park, Chan Kwon; Yoon, Hyung Kyu; Lee, Sook Young; Ahn, Joong Hyun; Moon, Hwa-Sik

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs) are thought to produce myofibroblasts through the epithelial to mesenchymal transition (EMT). Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation is associated with renal fibrosis during diabetes and liver fibrosis. RAGE is expressed at low basal levels in...

  16. Alveolocapillary model system to study alveolar re-epithelialization

    Energy Technology Data Exchange (ETDEWEB)

    Willems, Coen H.M.P.; Zimmermann, Luc J.I.; Sanders, Patricia J.L.T.; Wagendorp, Margot; Kloosterboer, Nico [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands); Cohen Tervaert, Jan Willem [Division of Clinical and Experimental Immunology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht (Netherlands); Duimel, Hans J.Q.; Verheyen, Fons K.C.P. [Electron Microscopy Unit, Department of Molecular Cell Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Iwaarden, J. Freek van, E-mail: f.vaniwaarden@maastrichtuniversity.nl [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands)

    2013-01-01

    In the present study an in vitro bilayer model system of the pulmonary alveolocapillary barrier was established to investigate the role of the microvascular endothelium on re-epithelialization. The model system, confluent monolayer cultures on opposing sides of a porous membrane, consisted of a human microvascular endothelial cell line (HPMEC-ST1.6R) and an alveolar type II like cell line (A549), stably expressing EGFP and mCherry, respectively. These fluorescent proteins allowed the real time assessment of the integrity of the monolayers and the automated analysis of the wound healing process after a scratch injury. The HPMECs significantly attenuated the speed of re-epithelialization, which was associated with the proximity to the A549 layer. Examination of cross-sectional transmission electron micrographs of the model system revealed protrusions through the membrane pores and close contact between the A549 cells and the HPMECs. Immunohistochemical analysis showed that these close contacts consisted of heterocellular gap-, tight- and adherens-junctions. Additional analysis, using a fluorescent probe to assess gap-junctional communication, revealed that the HPMECs and A549 cells were able to exchange the fluorophore, which could be abrogated by disrupting the gap junctions using connexin mimetic peptides. These data suggest that the pulmonary microvascular endothelium may impact the re-epithelialization process. -- Highlights: ► Model system for vital imaging and high throughput screening. ► Microvascular endothelium influences re-epithelialization. ► A549 cells form protrusions through membrane to contact HPMEC. ► A549 cells and HPMECs form heterocellular tight-, gap- and adherens-junctions.

  17. Radiologic assessment of alveolar and basal bone change of partially edentulous mandible

    International Nuclear Information System (INIS)

    The purpose of this study was to propose standard values for alveolar and basal bone in normal adult mandibles, and radiologically analyze the remodeling process of the edentulous mandible by examining molar areas and comparing them to the established normal values. Panoramic and CT scans of mandible were performed on 20 normal adults and 20 edentulous or partially edentulous adults. In both groups, arch half diameter and distance of alveolar bone were measured. Also the distance from the mandibular canal to the caudal edges, the buccal and lingual external borders of basal bone, were measured. A statistical comparison between the mean values of normal and edentulous mandibles was carried out in the selected areas. There was evidence of decreasing arch half diameter and distance in the edentulous mandible, but statistically no significant change was seen between the normal and edentulous alveolar bone. There was evidence of decreasing buccal basal bone and increasing in the lingual basal bone in the edentulous mandible. A statistically significant difference between normal and edentulous mandibles was noted in the buccal basal bone. There was an inward and forward atrophic change of the edentulous mandibular molar area compared to the control. CT scanning required the use of sophisticated and expensive procedures to analyze the remodeling process of edentulous mandibles. Consequently, the development and application of a more simplified and objective radiographic procedure for broad and long-term study of remodeling procedures of edentulous mandible was recommended.

  18. Radiologic assessment of alveolar and basal bone change of partially edentulous mandible

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chang Seo; Kim, Kee Deog [Yonsei University College of Dentistry, Seoul (Korea, Republic of)

    2002-09-15

    The purpose of this study was to propose standard values for alveolar and basal bone in normal adult mandibles, and radiologically analyze the remodeling process of the edentulous mandible by examining molar areas and comparing them to the established normal values. Panoramic and CT scans of mandible were performed on 20 normal adults and 20 edentulous or partially edentulous adults. In both groups, arch half diameter and distance of alveolar bone were measured. Also the distance from the mandibular canal to the caudal edges, the buccal and lingual external borders of basal bone, were measured. A statistical comparison between the mean values of normal and edentulous mandibles was carried out in the selected areas. There was evidence of decreasing arch half diameter and distance in the edentulous mandible, but statistically no significant change was seen between the normal and edentulous alveolar bone. There was evidence of decreasing buccal basal bone and increasing in the lingual basal bone in the edentulous mandible. A statistically significant difference between normal and edentulous mandibles was noted in the buccal basal bone. There was an inward and forward atrophic change of the edentulous mandibular molar area compared to the control. CT scanning required the use of sophisticated and expensive procedures to analyze the remodeling process of edentulous mandibles. Consequently, the development and application of a more simplified and objective radiographic procedure for broad and long-term study of remodeling procedures of edentulous mandible was recommended.

  19. Human alveolar epithelial type II cells in primary culture.

    Science.gov (United States)

    Mao, Pu; Wu, Songling; Li, Jianchun; Fu, Wei; He, Weiqun; Liu, Xiaoqing; Slutsky, Arthur S; Zhang, Haibo; Li, Yimin

    2015-02-01

    Alveolar epithelial type II (AEII) cells are a key structure and defender in the lung but also are the targets in many lung diseases, including acute respiratory distress syndrome, ventilator-induced lung injury, and pulmonary fibrosis. We sought to establish an optimized method for high yielding and long maintenance of characteristics of primary human AEII cells to facilitate the investigation of the mechanisms of lung diseases at the cellular and molecular levels. Adult human peripheral normal lung tissues of oncologic patients undergoing lung resection were collected. The AEII cells were isolated and identified by the expression of pro-surfactant protein (SP)C, epithelial sodium channel (αENaC) and cytokeratin (CK)-8, the lamellar bodies specific for AEII cells, and confirmed by the histology using electron microscopy. The phenotype of AEII cells was characterized by the expression of surfactant proteins (SP-A, SP-B, SP-C, SP-D), CK-8, KL-6, αENaC, and aquaporin (AQP)-3, which was maintained over 20 days. The biological activity of the primary human AEII cells producing SP-C, cytokines, and intercellular adhesion molecule-1 was vigorous in response to stimulation with tumor necrosis factor-α. We have modified previous methods and optimized a method for isolation of high purity and long maintenance of the human AEII cell phenotype in primary culture. This method provides an important tool for studies aiming at elucidating the molecular mechanisms of lung diseases exclusively in AEII cells. PMID:25677546

  20. Targeted Injury of Type II Alveolar Epithelial Cells Induces Pulmonary Fibrosis

    OpenAIRE

    Sisson, Thomas H.; Mendez, Michael; Choi, Karen; Subbotina, Natalya; Courey, Anthony; Cunningham, Andrew; Dave, Aditi; Engelhardt, John F.; Liu, Xiaoming; White, Eric S.; Thannickal, Victor J.; Bethany B Moore; Christensen, Paul J; Simon, Richard H

    2009-01-01

    Rationale: Ineffective repair of a damaged alveolar epithelium has been postulated to cause pulmonary fibrosis. In support of this theory, epithelial cell abnormalities, including hyperplasia, apoptosis, and persistent denudation of the alveolar basement membrane, are found in the lungs of humans with idiopathic pulmonary fibrosis and in animal models of fibrotic lung disease. Furthermore, mutations in genes that affect regenerative capacity or that cause injury/apoptosis of type II alveolar ...

  1. Type I Alveolar Epithelial Cells Mount Innate Immune Responses during Pneumococcal Pneumonia

    OpenAIRE

    Yamamoto, Kazuko; Ferrari, Joseph D.; Cao, Yuxia; Ramirez, Maria I.; Jones, Matthew R.; Quinton, Lee J.; Mizgerd, Joseph P.

    2012-01-01

    Pneumonia results from bacteria in the alveoli. The alveolar epithelium consists of type II cells, which secrete surfactant and associated proteins, and type I cells, which constitute 95% of the surface area and met anatomic and structural needs. Other than constitutively expressed surfactant proteins, it is unknown whether alveolar epithelial cells have distinct roles in innate immunity. Since innate immunity gene induction depends on NF-κB RelA (also known as p65) during pneumonia, we gener...

  2. Caffeic acid phenethyl ester protects lung alveolar epithelial cellsfrom cigarette smoke-induced damage

    OpenAIRE

    BARLAS, FIRAT BARIŞ; ERDOGAN, SUAT

    2015-01-01

    Background/aim: To evaluate the influence of caffeic acid phenethyl ester (CAPE) on cigarette smoke (CS)-induced cell damage, oxidative stress, and inflammation in human alveolar epithelial cells. Materials and methods: A549 alveolar epithelial cells were divided into control, CS exposure, CAPE, and CS+CAPE treatment groups. Undiluted CS-exposed medium (100%) and three dilutions (50%, 25%, and 10%) of CS-exposed media were applied to cultured A549 cells, which were analyzed after 3 h of inc...

  3. Interactions of 3 nm, 8 nm, and 15 nm gold particles with human alveolar epithelial cells : a microscopy study

    OpenAIRE

    Böse, Katharina

    2013-01-01

    The inhalation of nanoparticles can cause interactions with pulmonary structures. Human alveolar epithelial cells type II organize the alveolar epithelium and thus can be regarded as barrier against pulmonary nanoparticle uptake. Within the present work, interactions of differently sized gold nanoparticles with A549 cells, a model for type II human alveolar epithelial cells, were studied. The intracellular location of the fluorescently labeled gold particles was analyzed by STED (stimulated e...

  4. Cultured alveolar epithelial cells from septic rats mimic in vivo septic lung.

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    Taylor S Cohen

    Full Text Available Sepsis results in the formation of pulmonary edema by increasing in epithelial permeability. Therefore we hypothesized that alveolar epithelial cells isolated from septic animals develop tight junctions with different protein composition and reduced barrier function relative to alveolar epithelial cells from healthy animals. Male rats (200-300 g were sacrificed 24 hours after cecal ligation and double puncture (2CLP or sham surgery. Alveolar epithelial cells were isolated and plated on fibronectin-coated flexible membranes or permeable, non-flexible transwell substrates. After a 5 day culture period, cells were either lysed for western analysis of tight junction protein expressin (claudin 3, 4, 5, 7, 8, and 18, occludin, ZO-1, and JAM-A and MAPk (JNK, ERK, an p38 signaling activation, or barrier function was examined by measuring transepithelial resistance (TER or the flux of two molecular tracers (5 and 20 A. Inhibitors of JNK (SP600125, 20 microM and ERK (U0126, 10 microM were used to determine the role of these pathways in sepsis induced epithelial barrier dysfunction. Expression of claudin 4, claudin 18, and occludin was significantly lower, and activation of JNK and ERK signaling pathways was significantly increased in 2CLP monolayers, relative to sham monolayers. Transepithelial resistance of the 2CLP monolayers was reduced significantly compared to sham (769 and 1234 ohm-cm(2, respectively, however no significant difference in the flux of either tracer was observed. Inhibition of ERK, not JNK, significantly increased TER and expression of claudin 4 in 2CLP monolayers, and prevented significant differences in claudin 18 expression between 2CLP and sham monolayers. We conclude that alveolar epithelial cells isolated from septic animals form confluent monolayers with impaired barrier function compared to healthy monolayers, and inhibition of ERK signaling partially reverses differences between these monolayers. This model provides a unique

  5. Barrier-protective effects of activated protein C in human alveolar epithelial cells.

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    Ferranda Puig

    Full Text Available Acute lung injury (ALI is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI. We aimed to study the effects of activated protein C (APC on mechanical tension and barrier integrity in human alveolar epithelial cells (A549 exposed to thrombin. Cells were pretreated for 3 h with APC (50 µg/ml or vehicle (control. Subsequently, thrombin (50 nM or medium was added to the cell culture. APC significantly reduced thrombin-induced cell monolayer permeability, cell stiffening, and cell contraction, measured by electrical impedance, optical magnetic twisting cytometry, and traction microscopy, respectively, suggesting a barrier-protective response. The dynamics of the barrier integrity was also assessed by western blotting and immunofluorescence analysis of the tight junction ZO-1. Thrombin resulted in more elongated ZO-1 aggregates at cell-cell interface areas and induced an increase in ZO-1 membrane protein content. APC attenuated the length of these ZO-1 aggregates and reduced the ZO-1 membrane protein levels induced by thrombin. In conclusion, pretreatment with APC reduced the disruption of barrier integrity induced by thrombin, thus contributing to alveolar epithelial barrier protection.

  6. Clinical value of the alveolar epithelial permeability in various pulmonary diseases

    International Nuclear Information System (INIS)

    The authors have measured the pulmonary epithelial permeability in normals, smokers, ex-smokers and in various pulmonary diseases, using the sup(99m)Tc-DTPA monodisperse radioaerosol delivered by a newly designed nebulizer. Reference values for alveolar epithelial permeability were those of their own laboratory. Accelerated clearance of small idrophylic solutes from the lungs to the blood was found in smokers and in all the patients with idiopathic diffuse pulmonary fibrosis, chronic obstructive lung disease, congestive heart failure, acute viral pneumonia and adult respiratory distress syndrome. The greatest increase of alveolar epithelial clearance was found in the lung zone affected by the viral infection. The normal upper-lover lobe gradient of epithelial clearance was lost only in some patients. The increased permeability of the alveolar wall, although not specific, is characteristic and early feature of many acute and chronic pulmonary disease. For practical purposes, this parameter, rather than diagnostic, should be considered as a sensitive index of alveolar damage and repair, especially suitable for the follow-up of patients with spontaneous or therapeutic reversibility of parenchimal lung diseases. (orig.)

  7. Alveolar epithelial type II cells induce T cell tolerance to specific antigen

    DEFF Research Database (Denmark)

    Lo, Bernice; Hansen, Søren; Evans, Kathy; Heath, John K; Wright, Jo Rae

    2008-01-01

    The lungs face the immunologic challenge of rapidly eliminating inhaled pathogens while maintaining tolerance to innocuous Ags. A break in this immune homeostasis may result in pulmonary inflammatory diseases, such as allergies or asthma. The observation that alveolar epithelial type II cells (Ty...

  8. Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

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    Chen Yao

    2012-01-01

    Full Text Available Abstract Background Distal alveolar morphogenesis is marked by differentiation of alveolar type (AT-II to AT-I cells that give rise to the primary site of gas exchange, the alveolar/vascular interface. Endothelial-Monocyte Activating Polypeptide (EMAP II, an endogenous protein with anti-angiogenic properties, profoundly disrupts distal lung neovascularization and alveolar formation during lung morphogenesis, and is robustly expressed in the dysplastic alveolar regions of infants with Bronchopulmonary dysplasia. Determination as to whether EMAP II has a direct or indirect affect on ATII→ATI trans-differentiation has not been explored. Method In a controlled nonvascular environment, an in vitro model of ATII→ATI cell trans-differentiation was utilized to demonstrate the contribution that one vascular mediator has on distal epithelial cell differentiation. Results Here, we show that EMAP II significantly blocked ATII→ATI cell transdifferentiation by increasing cellular apoptosis and inhibiting expression of ATI markers. Moreover, EMAP II-treated ATII cells displayed myofibroblast characteristics, including elevated cellular proliferation, increased actin cytoskeleton stress fibers and Rho-GTPase activity, and increased nuclear:cytoplasmic volume. However, EMAP II-treated cells did not express the myofibroblast markers desmin or αSMA. Conclusion Our findings demonstrate that EMAP II interferes with ATII → ATI transdifferentiation resulting in a proliferating non-myofibroblast cell. These data identify the transdifferentiating alveolar cell as a possible target for EMAP II's induction of alveolar dysplasia.

  9. Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells.

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    Marco Checa

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive and lethal disease of unknown etiology. A growing body of evidence indicates that it may result from an aberrant activation of alveolar epithelium, which induces the expansion of the fibroblast population, their differentiation to myofibroblasts and the excessive accumulation of extracellular matrix. The mechanisms that activate the alveolar epithelium are unknown, but several studies indicate that smoking is the main environmental risk factor for the development of IPF. In this study we explored the effect of cigarette smoke on the gene expression profile and signaling pathways in alveolar epithelial cells. Lung epithelial cell line from human (A549, was exposed to cigarette smoke extract (CSE for 1, 3, and 5 weeks at 1, 5 and 10% and gene expression was evaluated by complete transcriptome microarrays. Signaling networks were analyzed with the Ingenuity Pathway Analysis software. At 5 weeks of exposure, alveolar epithelial cells acquired a fibroblast-like phenotype. At this time, gene expression profile revealed a significant increase of more than 1000 genes and deregulation of canonical signaling pathways such as TGF-β and Wnt. Several profibrotic genes involved in EMT were over-expressed, and incomplete EMT was observed in these cells, and corroborated in mouse (MLE-12 and rat (RLE-6TN epithelial cells. The secretion of activated TGF-β1 increased in cells exposed to cigarette smoke, which decreased when the integrin alpha v gene was silenced. These findings suggest that the exposure of alveolar epithelial cells to CSE induces the expression and release of a variety of profibrotic genes, and the activation of TGF-β1, which may explain at least partially, the increased risk of developing IPF in smokers.

  10. Regulation of epithelial sodium channel a-subunit expression by adenosine receptor A2a in alveolar epithelial cells

    Institute of Scientific and Technical Information of China (English)

    DENG Wang; WANG Dao-xin; ZHANG Wei; LI Chang-yi

    2011-01-01

    Background The amiloride-sensitive epithelial sodium channel a-subunit (a-ENaC) is an important factor for alveolar fluid clearance during acute lung injury. The relationship between adenosine receptor A2a (A2aAR) expressed in alveolar epithelial cells and aα-ENaC is poorly understood. We targeted the A2aAR in this study to investigate its role in the expression of αa-ENaC and in acute lung injury.Methods A549 cells were incubated with different concentrations of A2aAR agonist CGS-21680 and with 100 μmol/L CGS-21680 for various times. Rats were treated with lipopolysaccharide (LPS) after CGS-21680 was injected. Animals were sacrificed and tissue was harvested for evaluation of lung injury by analysis of the lung wet-to-dry weight ratio, lung permeability and myeloperoxidase activity. RT-PCR and Western blotting were used to determine the mRNA and protein expression levels of α-ENaC in A549 cells and alveolar type II epithelial cells.Results Both mRNA and protein levels of α-ENaC were markedly higher from 4 hours to 24 hours after exposure to 100μmol/L CGS-21680. There were significant changes from 0.1 umol/L to 100 μmol/L CGS-21680, with a positive correlation between increased concentrations of CGS-21680 and expression of α-ENaC. Treatment with CGS-21680during LPS induced lung injury protected the lung and promoted α-ENaC expression in the alveolar epithelial cells.Conclusion Activation of A2aAR has a protective effect during the lung injury, which may be beneficial to the prognosis of acute lung injury.

  11. Alveolar epithelial permeability in patients with primary spontaneous pneumothorax as determined by Tc-99m DTPA aerosol scintigraphy

    International Nuclear Information System (INIS)

    Primary spontaneous pneumothorax (PSP) occurs subsequent to a disruption in the continuity of visceral pleura and escape of air into the pleural space. The cause of PSP is most often the rupture of subpleural blebs or bullae. It is usually difficult to detect evidence of pulmonary pathology. The purposes of the present study were to investigate the changes of pulmonary alveolar epithelial permeability in patients with PSP as determined by Tc-99m DTPA aerosol lung scintigraphy, to assess whether or not some differences exist between apical and basal parts of the lungs, and to determine the relationship between the clearance rate of Tc-99m DTPA and the pulmonary function test (PFT) results, the recurrence rate of PSP, and the percentage of pneumothorax in affected lung. Thirteen PSP patients (two females, 11 males; mean age 32.5±11.8 years) with normal chest X-ray were studied. Thirteen healthy non-smoking volunteers (1 female, 12 males; mean age, 35.8±10 years) were selected as a control group. Tc-99m DTPA aerosol lung scintigraphy and PFT were performed in all patients and controls. Clearance rates (%/min) of Tc-99m DTPA aerosol in right and left lung field, and apical and basal parts of each lung were calculated from dynamic images for 15 min. There was no significant difference (p>0.05) between patients and controls, or between apical and basal parts of each lung. No correlation was found between the clearance rate of Tc-99m DTPA and PFT results, the recurrence rate of PSP, or the percentage of pneumothorax. This study demonstrates that pulmonary epithelial permeability is not altered in PSP patients; the clearance rate of Tc-99m DTPA shows no difference between apical and basal parts of each lung. (author)

  12. Alveolar epithelial stem and progenitor cells: emerging evidence for their role in lung regeneration.

    Science.gov (United States)

    Hoffman, A M; Ingenito, E P

    2012-01-01

    Lung injuries that impact the alveolus, such as emphysema, pulmonary fibrosis, and acute lung injury, are costly and prevalent problems. Moreover, the extent of alveolar injury and impairment of gas exchange is strongly associated with prognosis and survival. Thus, mechanisms of repair and regeneration of the lung alveolar compartment have received mounting attention as newer approaches to the study of stem and progenitor cells in this region unfold. The role of type II alveolar epithelial as the sole source of type I (AECI) and II (AECII) alveolar epithelial cells following lung injury has been recently challenged; recently, investigators have described stemprogenitor cells that function like precursors to AECII either in vitro or in vivo, both in mice and humans. Techniques to explore selfrenewal and multipotency have been rigorously applied to these putative stem-progenitor cell populations and the data thus far is compelling. This review provides background to the study of alveolar regeneration with the aim to provide context to the recent discoveries of putative stem-progenitor cells that may contribute to this process. PMID:23016551

  13. NO2 decreases paracellular resistance to ion and solute flow in alveolar epithelial monolayers

    International Nuclear Information System (INIS)

    Primary cultured monolayers of rat alveolar epithelial cells grown on tissue culture-treated Nuclepore filters were exposed to 2.5 ppm nitrogen dioxide NO2 for 2-20 min. Changes in monolayer bioelectric properties and solute permeabilities were subsequently measured. Exposure to NO2 produced a dose-dependent decrease in monolayer transepithelial electrical resistance (Rt), whereas monolayer short-circuit current was unaffected. Post-exposure monolayer permeability to 14C-sucrose (which primarily crosses alveolar epithelium via the paracellular pathway) increased markedly. That for 3H-glycerol (which permeates through both paracellular and transcellular pathways) increased to a lesser extent. Partial recovery of Rt and solute permeabilities was noted by 48-h post-exposure. The time courses of the decrease in Rt and increase in solute permeabilities were similar. These results suggest that NO2 primarily impairs passive alveolar epithelial barrier functions in vitro, probably by altering intercellular junctions, and does not appear to directly affect cell membrane active ion transport processes. When correlated with results obtained from experimental approaches, studies of in vitro alveolar epithelial monolayers may facilitate investigations of dosimetry, sites, and mechanisms of oxidant injury in the lung

  14. Glucose-6-phosphate dehydrogenase in rat lung alveolar epithelial cells. An ultrastructural enzyme-cytochemical study

    Directory of Open Access Journals (Sweden)

    S Matsubara

    2010-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is the key enzyme of the pentose phosphate pathway in carbohydrate metabolism, and it plays an important role in cell proliferation and antioxidant regulation within cells in various organs. Although marked cell proliferation and oxidant/antioxidant metabolism occur in lung alveolar epithelial cells, definite data has been lacking as to whether cytochemically detectable G6PD is present in alveolar epithelial cells. The distribution pattern of G6PD within these cells, if it is present, is also unknown. The purpose of the present study was to investigate the subcellular localization of G6PD in alveolar cells in the rat lung using a newly- developed enzyme-cytochemistry (copper-ferrocyanide method. Type I cells and stromal endothelia and fibroblasts showed no activities. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of type II alveolar epithelial cells. The cytochemical controls ensured specific detection of enzyme activity. This enzyme may play a role in airway defense by delivering substances for cell proliferation and antioxidant forces, thus maintaining the airway architecture.

  15. Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells.

    Science.gov (United States)

    Sweeney, Sinbad; Leo, Bey Fen; Chen, Shu; Abraham-Thomas, Nisha; Thorley, Andrew J; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng Jim; Shaffer, Milo S P; Chung, Kian Fan; Ryan, Mary P; Porter, Alexandra E; Tetley, Teresa D

    2016-09-01

    Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf(®) (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity. We demonstrated that 20nm citrate-capped AgNPs induce toxicity in human alveolar type I-like epithelial cells and, in agreement with our hypothesis, that pulmonary surfactant acts to mitigate this toxicity, possibly through reducing AgNP dissolution into cytotoxic Ag(+) ions. For example, IL-6 and IL-8 release by TT1 cells significantly increased 10.7- and 35-fold, respectively (P<0.01), 24h after treatment with 25μg/ml AgNPs. In contrast, following pre-incubation of AgNPs with Curosurf(®), this effect was almost completely abolished. We further determined that the mechanism of this toxicity is likely associated with Ag(+) ion release and lysosomal disruption, but not with increased reactive oxygen species generation. This study provides a critical understanding of the toxicity of AgNPs in target human alveolar type-I-like epithelial cells and the role of pulmonary surfactant in mitigating this toxicity. The observations reported have important implications for the manufacture and application of AgNPs, in particular for applications involving use of aerosolised AgNPs. PMID:27182651

  16. Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells

    OpenAIRE

    LI Hong; Xiang, Zheng; Feng, Ting; Li, Jinrong; Liu, Yinping; Fan, Yingying; Lu, Qiao; Yin, Zhongwei; Yu, Meixing; Shen, Chongyang; Tu, Wenwei

    2013-01-01

    γδ-T cells play an indispensable role in host defense against different viruses, including influenza A virus. However, whether these cells have cytotoxic activity against influenza virus-infected lung alveolar epithelial cells and subsequently contribute to virus clearance remains unknown. Using influenza virus-infected A549 cells, human lung alveolar epithelial cells, we investigated the cytotoxic activity of aminobisphosphonate pamidronate (PAM)-expanded human Vγ9Vδ2-T cells and their under...

  17. Expression and function of aquaporin-1 in hyperoxia-exposed alveolar epithelial type II cells

    OpenAIRE

    ZHANG, QIU-YUE; Fu, Jian-Hua(Department of Physics, Henan University of Technology, Zhengzhou 450001, China); XUE, XIN-DONG

    2014-01-01

    The aim of the present study was to investigate water transport dysfunction in alveolar epithelial type II cells (AECII), which were exposed to hyperoxia, and to investigate the mechanism of pulmonary edema resulting from hyperoxic lung injury. The lung cells of newborn rats were isolated for primary cell culture and divided into control and experimental groups. The control and experimental group cells were placed into a normoxic incubator (oxygen volume fraction, 0.21) or hyperoxic incubator...

  18. The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis

    OpenAIRE

    Seok-Jo Kim; Paul Cheresh; Jablonski, Renea P.; Williams, David B.; Kamp, David W.

    2015-01-01

    Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). The mammalian mitochondrial DNA (mtDNA) encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidenc...

  19. Cell Stress Induces Upregulation of Osteopontin via the ERK Pathway in Type II Alveolar Epithelial Cells

    OpenAIRE

    Aki Kato; Takafumi Okura; Chizuru Hamada; Seigo Miyoshi; Hitoshi Katayama; Jitsuo Higaki; Ryoji Ito

    2014-01-01

    Osteopontin (OPN) is a multifunctional protein that plays important roles in cell growth, differentiation, migration and tissue fibrosis. In human idiopathic pulmonary fibrosis and murine bleomycin-induced lung fibrosis, OPN is upregulated in type II alveolar epithelial cells (AEC II). However, the mechanism of OPN induction in AEC II is not fully understood. In this study, we demonstrate the molecular mechanism of OPN induction in AEC II and elucidate the functions of OPN in AEC II and lung ...

  20. Biophysical determinants of alveolar epithelial plasma membrane wounding associated with mechanical ventilation.

    Science.gov (United States)

    Hussein, Omar; Walters, Bruce; Stroetz, Randolph; Valencia, Paul; McCall, Deborah; Hubmayr, Rolf D

    2013-10-01

    Mechanical ventilation may cause harm by straining lungs at a time they are particularly prone to injury from deforming stress. The objective of this study was to define the relative contributions of alveolar overdistension and cyclic recruitment and "collapse" of unstable lung units to membrane wounding of alveolar epithelial cells. We measured the interactive effects of tidal volume (VT), transpulmonary pressure (PTP), and of airspace liquid on the number of alveolar epithelial cells with plasma membrane wounds in ex vivo mechanically ventilated rat lungs. Plasma membrane integrity was assessed by propidium iodide (PI) exclusion in confocal images of subpleural alveoli. Cyclic inflations of normal lungs from zero end-expiratory pressure to 40 cmH2O produced VT values of 56.9 ± 3.1 ml/kg and were associated with 0.12 ± 0.12 PI-positive cells/alveolus. A preceding tracheal instillation of normal saline (3 ml) reduced VT to 49.1 ± 6 ml/kg but was associated with a significantly greater number of wounded alveolar epithelial cells (0.52 ± 0.16 cells/alveolus; P < 0.01). Mechanical ventilation of completely saline-filled lungs with saline (VT = 52 ml/kg) to pressures between 10 and 15 cmH2O was associated with the least number of wounded epithelial cells (0.02 ± 0.02 cells/alveolus; P < 0.01). In mechanically ventilated, partially saline-filled lungs, the number of wounded cells increased substantially with VT, but, once VT was accounted for, wounding was independent of maximal PTP. We found that interfacial stress associated with the generation and destruction of liquid bridges in airspaces is the primary biophysical cell injury mechanism in mechanically ventilated lungs. PMID:23997173

  1. Generation of Alveolar Epithelial Spheroids via Isolated Progenitor Cells from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Shimpei Gotoh

    2014-09-01

    Full Text Available No methods for isolating induced alveolar epithelial progenitor cells (AEPCs from human embryonic stem cells (hESCs and induced pluripotent stem cells (hiPSCs have been reported. Based on a study of the stepwise induction of alveolar epithelial cells (AECs, we identified carboxypeptidase M (CPM as a surface marker of NKX2-1+ “ventralized” anterior foregut endoderm cells (VAFECs in vitro and in fetal human and murine lungs. Using SFTPC-GFP reporter hPSCs and a 3D coculture system with fetal human lung fibroblasts, we showed that CPM+ cells isolated from VAFECs differentiate into AECs, demonstrating that CPM is a marker of AEPCs. Moreover, 3D coculture differentiation of CPM+ cells formed spheroids with lamellar-body-like structures and an increased expression of surfactant proteins compared with 2D differentiation. Methods to induce and isolate AEPCs using CPM and consequently generate alveolar epithelial spheroids would aid human pulmonary disease modeling and regenerative medicine.

  2. Dexmedetomidine Attenuates Oxidative Stress Induced Lung Alveolar Epithelial Cell Apoptosis In Vitro

    Directory of Open Access Journals (Sweden)

    Jian Cui

    2015-01-01

    Full Text Available Background. Oxidative stress plays a pivotal role in the lung injuries of critical ill patients. This study investigates the protection conferred by α2 adrenoceptor agonist dexmedetomidine (Dex from lung alveolar epithelial cell injury induced by hydrogen peroxide (H2O2 and the underlying mechanisms. Methods. The lung alveolar epithelial cell line, A549, was cultured and then treated with 500 μM H2O2 with or without Dex (1 nM or Dex in combination with atipamezole (10 nM, an antagonist of α2 receptors. Their effect on mitochondrial membrane potential (Δψm, reactive oxygen species (ROS, and the cell cycle was assessed by flow cytometry. Cleaved-caspases 3 and 9, BAX, Bcl-2, phospho-mTOR (p-mTOR, ERK1/2, and E-cadherin expression were also determined with immunocytochemistry. Results. Upregulation of cleaved-caspases 3 and 9 and BAX and downregulation of Bcl-2, p-mTOR, and E-cadherin were found following H2O2 treatment, and all of these were reversed by Dex. Dex also prevented the ROS generation, cytochrome C release, and cell cycle arrest induced by H2O2. The effects of Dex were partially reversed by atipamezole. Conclusion. Our study demonstrated that Dex protected lung alveolar epithelial cells from apoptotic injury, cell cycle arrest, and loss of cell adhesion induced by H2O2 through enhancing the cell survival and proliferation.

  3. TGF-β1 induces human alveolar epithelial to mesenchymal cell transition (EMT

    Directory of Open Access Journals (Sweden)

    Kamimura Takashi

    2005-06-01

    Full Text Available Abstract Background Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF. They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA, and expression of epithelial phenotypic markers including E-cadherin (E-cad. Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2

  4. A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells.

    Science.gov (United States)

    Wang, Dachun; Haviland, David L; Burns, Alan R; Zsigmond, Eva; Wetsel, Rick A

    2007-03-13

    Alveolar epithelial type II (ATII) cells are small, cuboidal cells that constitute approximately 60% of the pulmonary alveolar epithelium. These cells are crucial for repair of the injured alveolus by differentiating into alveolar epithelial type I cells. ATII cells derived from human ES (hES) cells are a promising source of cells that could be used therapeutically to treat distal lung diseases. We have developed a reliable transfection and culture procedure, which facilitates, via genetic selection, the differentiation of hES cells into an essentially pure (>99%) population of ATII cells (hES-ATII). Purity, as well as biological features and morphological characteristics of normal ATII cells, was demonstrated for the hES-ATII cells, including lamellar body formation, expression of surfactant proteins A, B, and C, alpha-1-antitrypsin, and the cystic fibrosis transmembrane conductance receptor, as well as the synthesis and secretion of complement proteins C3 and C5. Collectively, these data document the successful generation of a pure population of ATII cells derived from hES cells, providing a practical source of ATII cells to explore in disease models their potential in the regeneration and repair of the injured alveolus and in the therapeutic treatment of genetic diseases affecting the lung. PMID:17360544

  5. 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

  6. CAMK1D amplification implicated in epithelial-mesenchymal transition in basal-like breast cancer

    OpenAIRE

    Bergamaschi, Anna; Kim, Young H.; Kwei, Kevin A; La Choi, Yoon; Bocanegra, Melanie; Langerod, Anita; Han, Wonshik; Noh, Dong-Young; Huntsman, David G.; Jeffrey, Stefanie S.; Borresen-Dale, Anne-Lise; Pollack, Jonathan R

    2008-01-01

    Breast cancer exhibits clinical and molecular heterogeneity, where expression-profiling studies have identified five major molecular subtypes. The basal-like subtype, expressing basal epithelial markers and negative for estrogen receptor (ER), progesterone receptor (PR) and HER2, is associated with higher overall levels of DNA copy number alteration (CNA), specific CNAs (like gain on chromosome 10p), and poor prognosis. Discovering the molecular genetic basis of tumor subtypes may provide new...

  7. Conditional deletion of epithelial IKKβ impairs alveolar formation through apoptosis and decreased VEGF expression during early mouse lung morphogenesis

    Directory of Open Access Journals (Sweden)

    Li Changgong

    2011-10-01

    Full Text Available Abstract Background Alveolar septation marks the beginning of the transition from the saccular to alveolar stage of lung development. Inflammation can disrupt this process and permanently impair alveolar formation resulting in alveolar hypoplasia as seen in bronchopulmonary dysplasia in preterm newborns. NF-κB is a transcription factor central to multiple inflammatory and developmental pathways including dorsal-ventral patterning in fruit flies; limb, mammary and submandibular gland development in mice; and branching morphogenesis in chick lungs. We have previously shown that epithelial overexpression of NF-κB accelerates lung maturity using transgenic mice. The purpose of this study was to test our hypothesis that targeted deletion of NF-κB signaling in lung epithelium would impair alveolar formation. Methods We generated double transgenic mice with lung epithelium-specific deletion of IKKβ, a known activating kinase upstream of NF-κB, using a cre-loxP transgenic recombination strategy. Lungs of resulting progeny were analyzed at embryonic and early postnatal stages to determine specific effects on lung histology, and mRNA and protein expression of relevant lung morphoreulatory genes. Lastly, results measuring expression of the angiogenic factor, VEGF, were confirmed in vitro using a siRNA-knockdown strategy in cultured mouse lung epithelial cells. Results Our results showed that IKKβ deletion in the lung epithelium transiently decreased alveolar type I and type II cells and myofibroblasts and delayed alveolar formation. These effects were mediated through increased alveolar type II cell apoptosis and decreased epithelial VEGF expression. Conclusions These results suggest that epithelial NF-κB plays a critical role in early alveolar development possibly through regulation of VEGF.

  8. Establishment and evaluation of a stable cattle type II alveolar epithelial cell line.

    Directory of Open Access Journals (Sweden)

    Feng Su

    Full Text Available Macrophages and dendritic cells are recognized as key players in the defense against mycobacterial infection. Recent research has confirmed that alveolar epithelial cells (AECs also play important roles against mycobacterium infections. Thus, establishing a stable cattle AEC line for future endogenous immune research on bacterial invasion is necessary. In the present study, we first purified and immortalized type II AECs (AEC II cells by transfecting them with a plasmid containing the human telomerase reverse trancriptase gene. We then tested whether or not the immortalized cells retained the basic physiological properties of primary AECs by reverse-transcription polymerase chain reaction and Western blot. Finally, we tested the secretion capacity of immortalized AEC II cells upon stimulation by bacterial invasion. The cattle type II alveolar epithelial cell line (HTERT-AEC II that we established retained lung epithelial cell characteristics: the cells were positive for surfactants A and B, and they secreted tumor necrosis factor-α and interleukin-6 in response to bacterial invasion. Thus, the cell line we established is a potential tool for research on the relationship between AECs and Mycobacterium tuberculosis.

  9. Breakdown of Epithelial Barrier Integrity and Overdrive Activation of Alveolar Epithelial Cells in the Pathogenesis of Acute Respiratory Distress Syndrome and Lung Fibrosis

    OpenAIRE

    Shigehisa Yanagi; Hironobu Tsubouchi; Ayako Miura; Nobuhiro Matsumoto; Masamitsu Nakazato

    2015-01-01

    Individual alveolar epithelial cells (AECs) collaboratively form a tight barrier between atmosphere and fluid-filled tissue to enable normal gas exchange. The tight junctions of AECs provide intercellular sealing and are integral to the maintenance of the AEC barrier integrity. Disruption and failure of reconstitution of AEC barrier result in catastrophic consequences, leading to alveolar flooding and subsequent devastating fibrotic scarring. Recent evidences reveal that many of the fibrotic ...

  10. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells

    Science.gov (United States)

    Sweeney, Sinbad; Theodorou, Ioannis G.; Zambianchi, Marta; Chen, Shu; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng (Jim); Chung, Kian Fan; Shaffer, Milo S. P.; Ryan, Mary P.; Porter, Alexandra E.; Tetley, Teresa D.

    2015-06-01

    Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit.Inhaled nanoparticles have a high deposition rate in

  11. Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias

    Directory of Open Access Journals (Sweden)

    Kajiki Akira

    2011-03-01

    Full Text Available Abstract Background It is difficult to predict survival in patients with idiopathic pulmonary fibrosis. Recently, several proteins, such as surfactant protein (SP and KL-6, have been reported to be useful biologic markers for prediction of prognosis for interstitial pneumonias. It is not clear whether there is any relationship between expression of these proteins in regenerative/hyperplastic alveolar epithelial cells and prognosis of idiopathic interstitial pneumonias (IIPs. Objectives This study aimed to elucidate the clinical significance of the expression of such lung secretory proteins as SP-A and KL-6 in lung tissues of patients with IIPs. Methods We retrospectively investigated the immunohistochemical expression of SP-A, KL-6, cytokeratin (CK, and epithelial membrane antigen (EMA in alveolar epithelial cells in lung tissues obtained from surgical lung biopsy in 43 patients with IIPs, and analyzed the correlation between expression of these markers and the prognosis of each IIP patient. CK and EMA were used as general markers for epithelial cells. Results In patients with usual interstitial pneumonia (UIP, the ratio of SP-A positive epithelial cells to all alveolar epithelial cells (SP-A positive ratio in the collapsed and mural fibrosis areas varied, ranging from cases where almost all alveolar epithelial cells expressed SP-A to cases where only a few did. On the other hand, in many patients with nonspecific interstitial pneumonia (NSIP, many of the alveolar epithelial cells in the diseased areas expressed SP-A. The SP-A positive ratio was significantly lower in patients who died from progression of UIP than in patients with UIP who remained stable or deteriorated but did not die. In NSIP patients, a similar tendency was noted between the SP-A positive ratio and prognosis. Conclusions The results suggest that the paucity of immunohistochemical SP-A expression in alveolar epithelial cells in diseased areas (i.e. regenerative

  12. Cigarette Smoke Extract Inhibits the Proliferation of Alveolar Epithelial Cells and Augments the Expression of P21WAF1

    Institute of Scientific and Technical Information of China (English)

    Zongxian JIAO; Qilin AO; Xiaona GE; Mi XIONG

    2008-01-01

    Cigarette smoking is intimately related with the development of chronic obstructive pulmonary diseases, and alveolar epithelium is a major target for the exposure of cigarette smoke ex- tract. In order to investigate the effect of cigarette smoke extract on the proliferation of alveolar epithelial cell type Ⅱand its relationship with P21WAF1, the alveolar epithelial type Ⅱ cell line (A549) cells were chosen as surrogate cells to represent alveolar epithelial type Ⅱ cells. MTT assay was used to detect cell viability after interfered with different concentrations of cigarette smoke ex-tract. It was observed cigarette smoke extract inhibited the growth of A549 cells in a dose- and time-dependent manner. The morphological changes, involving the condensation and margination of nuclear chromatin, even karyorrhexis, were observed by both Hoechst staining and electronic mi-croscopy. Flow cytometry analysis demonstrated the increased cell percentages in G1 and subG1phases after the cells were incubated with cigarette smoke extract. The expression of p21WAF1 protein and mRNA was also significantly increased as detected by the methods of Western blot or reverse transcription-polymerase chain reaction respectively. In conclusion, cigarette smoke extract inhibits the proliferation of alveolar epithelial cell type Ⅱ and blocks them in G1/S phase. The intracellular accumulation of P21WAF1 may be one of the mechanisms which contribute to cigarette smoke ex-tract-induced inhibition of cell proliferation.

  13. FXYD1 negatively regulates Na(+)/K(+)-ATPase activity in lung alveolar epithelial cells.

    Science.gov (United States)

    Wujak, Łukasz A; Blume, Anna; Baloğlu, Emel; Wygrecka, Małgorzata; Wygowski, Jegor; Herold, Susanne; Mayer, Konstantin; Vadász, István; Besuch, Petra; Mairbäurl, Heimo; Seeger, Werner; Morty, Rory E

    2016-01-01

    Acute respiratory distress syndrome (ARDS) is clinical syndrome characterized by decreased lung fluid reabsorption, causing alveolar edema. Defective alveolar ion transport undertaken in part by the Na(+)/K(+)-ATPase underlies this compromised fluid balance, although the molecular mechanisms at play are not understood. We describe here increased expression of FXYD1, FXYD3 and FXYD5, three regulatory subunits of the Na(+)/K(+)-ATPase, in the lungs of ARDS patients. Transforming growth factor (TGF)-β, a pathogenic mediator of ARDS, drove increased FXYD1 expression in A549 human lung alveolar epithelial cells, suggesting that pathogenic TGF-β signaling altered Na(+)/K(+)-ATPase activity in affected lungs. Lentivirus-mediated delivery of FXYD1 and FXYD3 allowed for overexpression of both regulatory subunits in polarized H441 cell monolayers on an air/liquid interface. FXYD1 but not FXYD3 overexpression inhibited amphotericin B-sensitive equivalent short-circuit current in Ussing chamber studies. Thus, we speculate that FXYD1 overexpression in ARDS patient lungs may limit Na(+)/K(+)-ATPase activity, and contribute to edema persistence. PMID:26410457

  14. Electron microscopic studies of various cells in the alveolar wall of mice with special reference to spheroid alveolar epithelial cells after intravenous injection of squid-ink (sepia-melanin solution

    Directory of Open Access Journals (Sweden)

    Suwa,Kiichi

    1977-02-01

    Full Text Available The effect of an intravenous injection of squid-ink (sepia-melanin solution on adult mouse spheroid alveolar epithelial cells was observed by the electron microscope. Sepia-melanin particles were seen in all alveolar wall cells examined that seems to suggest the entrance of sepia-melanin particles into the spheroid alveolar epithlial cells from the alveolar blood capillary. In cases of large penetrations of sepia-melanin particles into spheroid alveolar epithelial cells, a greater increase was found in the intramitochondrial granules. In addition, the so-called inclusion body believed to be formed by the degeneration of mitochondria had very high electron density and its quantity was abundant. On the contrary, in cases where the quantity of sepia-melanin entrance into the spheroid alveolar epithelial cell was small, neither an increase of intramitochondrial granules, an increase of the electron density nor an increase in the quantity of specific inclusion body was found.

  15. Role of cytoskeleton in cytokine production from lung alveolar epithelial cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Cytokines are involved in both host defense and inflammatory lung injury. Recent work from our laboratory and others has demonstrated that in addition to classical immune cells, lung alveolar epithelial cells (or pneumocytes) can also produce cytokines in response to various stimuli. This new knowledge has advanced our view of the host defense system in the lung. The regulatory mechanisms of cytokine production have been studied in great detail at various cellular and molecular levels, but the mechanisms of intracellular cytokine transport are largely unknown. Our recent studies suggest that the cytoskeleton could play an important role in mediating intracellular cytokine trafficking. This could be an important regulatory step for cytokine production. For example, lipopolyssacharide (LPS) induced tumor necrosis factor-α (TNF-α) from rat pneumocytes, which was further enhanced by a microfilament-disrupting agent. LPS also induced macrophage inflammatory protein-2(MIP-2), a chemokine for neutrophil recruitment and activation, from rat pneumocytes. This effect was enhanced by microtubule-disrupting agents. We speculate that both microfilaments and microtubules are involved in regulating cytokine transportation in pneumocytes through different mechanisms. Further investigation in on going in my laboratory. From a clinical perspective, if we understand the mechanisms regulating cytokine production and release from lung alveolar epithelial cells, we may be able to enhance or inhibit release of crucial cytokines depending on the clinical situation.

  16. MicroRNA 16 Modulates Epithelial Sodium Channel in Human Alveolar Epithelial Cells

    OpenAIRE

    Parthasarathy, Prasanna Tamarapu; Galam, Lakshmi; Huynh, Bao; Yunus, Asfiya; Abuelenen, Toaa; Castillo, Annie; Ramanathan, Gurukumar Kollongod; Ruan, Cox; Kolliputi, Narasaiah

    2012-01-01

    Acute lung injury (ALI) is a devastating disease characterized by pulmonary edema. Removal of edema from the air spaces is a critical function of the epithelial sodium channel (ENaC) in ALI. The molecular mechanisms behind resolution of pulmonary edema are incompletely understood. MicroRNA’s (miRNA) are crucial gene regulators and are dysregulated in various diseases including ALI. Recent studies suggest that microRNA-16 (miR-16) targets serotonin transporter (SERT) involved in the serotonin ...

  17. Mesenchymal stem cells protect from hypoxia-induced alveolar epithelial-mesenchymal transition.

    Science.gov (United States)

    Uzunhan, Yurdagül; Bernard, Olivier; Marchant, Dominique; Dard, Nicolas; Vanneaux, Valérie; Larghero, Jérôme; Gille, Thomas; Clerici, Christine; Valeyre, Dominique; Nunes, Hilario; Boncoeur, Emilie; Planès, Carole

    2016-03-01

    Administration of bone marrow-derived human mesenchymal stem cells (hMSC) reduces lung inflammation, fibrosis, and mortality in animal models of lung injury, by a mechanism not completely understood. We investigated whether hMSC would prevent epithelial-mesenchymal transition (EMT) induced by hypoxia in primary rat alveolar epithelial cell (AEC). In AEC cultured on semipermeable filters, prolonged hypoxic exposure (1.5% O2 for up to 12 days) induced phenotypic changes consistent with EMT, i.e., a change in cell morphology, a decrease in transepithelial resistance (Rte) and in the expression of epithelial markers [zonula occludens-1 (ZO-1), E-cadherin, AQP-5, TTF-1], together with an increase in mesenchymal markers [vimentin, α-smooth muscle actin (α-SMA)]. Expression of transcription factors driving EMT such as SNAIL1, ZEB1, and TWIST1 increased after 2, 24, and 48 h of hypoxia, respectively. Hypoxia also induced TGF-β1 mRNA expression and the secretion of active TGF-β1 in apical medium, and the expression of connective tissue growth factor (CTGF), two inducers of EMT. Coculture of AEC with hMSC partially prevented the decrease in Rte and in ZO-1, E-cadherin, and TTF-1 expression, and the increase in vimentin expression induced by hypoxia. It also abolished the increase in TGF-β1 expression and in TGF-β1-induced genes ZEB1, TWIST1, and CTGF. Finally, incubation with human recombinant KGF at a concentration similar to what was measured in hMSC-conditioned media restored the expression of TTF-1 and prevented the increase in TWIST1, TGF-β1, and CTGF in hypoxic AEC. Our results indicate that hMSC prevent hypoxia-induced alveolar EMT through the paracrine modulation of EMT signaling pathways and suggest that this effect is partly mediated by KGF. PMID:26702148

  18. Hypoxia-induced alveolar epithelial-mesenchymal transition requires mitochondrial ROS and hypoxia-inducible factor 1

    OpenAIRE

    Zhou, Guofei; Dada, Laura A.; Wu, Minghua; Kelly, Aileen; Trejo, Humberto; Zhou, Qiyuan; Varga, John; Sznajder, Jacob I.

    2009-01-01

    Patients with acute lung injury develop hypoxia, which may lead to lung dysfunction and aberrant tissue repair. Recent studies have suggested that epithelial-mesenchymal transition (EMT) contributes to pulmonary fibrosis. We sought to determine whether hypoxia induces EMT in alveolar epithelial cells (AEC). We found that hypoxia induced the expression of α-smooth muscle actin (α-SMA) and vimentin and decreased the expression of E-cadherin in transformed and primary human, rat, and mouse AEC, ...

  19. CXCR4 regulates migration of lung alveolar epithelial cells through activation of Rac1 and matrix metalloproteinase-2

    OpenAIRE

    Ghosh, Manik C.; Makena, Patrudu S.; Gorantla, Vijay; Sinclair, Scott E.; Waters, Christopher M.

    2012-01-01

    Restoration of the epithelial barrier following acute lung injury is critical for recovery of lung homeostasis. After injury, alveolar type II epithelial (ATII) cells spread and migrate to cover the denuded surface and, eventually, proliferate and differentiate into type I cells. The chemokine CXCL12, also known as stromal cell-derived factor 1α, has well-recognized roles in organogenesis, hematopoiesis, and immune responses through its binding to the chemokine receptor CXCR4. While CXCL12/CX...

  20. CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells.

    Science.gov (United States)

    Toya, Mika; Kobayashi, Saeko; Kawasaki, Miwa; Shioi, Go; Kaneko, Mari; Ishiuchi, Takashi; Misaki, Kazuyo; Meng, Wenxiang; Takeichi, Masatoshi

    2016-01-12

    Polarized epithelial cells exhibit a characteristic array of microtubules that are oriented along the apicobasal axis of the cells. The minus-ends of these microtubules face apically, and the plus-ends face toward the basal side. The mechanisms underlying this epithelial-specific microtubule assembly remain unresolved, however. Here, using mouse intestinal cells and human Caco-2 cells, we show that the microtubule minus-end binding protein CAMSAP3 (calmodulin-regulated-spectrin-associated protein 3) plays a pivotal role in orienting the apical-to-basal polarity of microtubules in epithelial cells. In these cells, CAMSAP3 accumulated at the apical cortices, and tethered the longitudinal microtubules to these sites. Camsap3 mutation or depletion resulted in a random orientation of these microtubules; concomitantly, the stereotypic positioning of the nucleus and Golgi apparatus was perturbed. In contrast, the integrity of the plasma membrane was hardly affected, although its structural stability was decreased. Further analysis revealed that the CC1 domain of CAMSAP3 is crucial for its apical localization, and that forced mislocalization of CAMSAP3 disturbs the epithelial architecture. These findings demonstrate that apically localized CAMSAP3 determines the proper orientation of microtubules, and in turn that of organelles, in mature mammalian epithelial cells. PMID:26715742

  1. Isolation and characterization of alveolar epithelial type II cells derived from mouse embryonic stem cells.

    Science.gov (United States)

    Sun, Huanhuan; Quan, Yuan; Yan, Qing; Peng, Xinmiao; Mao, Zhengmei; Wetsel, Rick A; Wang, Dachun

    2014-06-01

    The use of embryonic stem cells (ESCs) to regenerate distal lung epithelia damaged by injuries or diseases requires development of safe and efficient methodologies that direct ESC differentiation into transplantable distal lung epithelial progenitors. Time-consuming culture procedure and low differentiation efficiency are major problems that are associated with conventional differentiation approaches via embryoid body formation. The use of a growth factor cocktail or a lung-specific cell-conditioned medium to enrich definitive endoderm for efficient differentiation of mouse ESCs (mESC) into alveolar epithelial progenitor type II cells (ATIICs) has been reported, but not yet successful for generating a homogenous population of ATIICs for tissue regeneration purpose, and it remains unclear whether or not those mESC-derived ATIICs possess normal biological functions. Here, we report a novel method using a genetically modified mESC line harboring an ATIIC-specific neomycin(R) transgene in Rosa 26 locus. We showed that ATIICs can be efficiently differentiated from mESCs as early as day 7 by culturing them directly on Matrigel-coated plates in DMEM containing 15% knockout serum replacement. With this culture condition, the genetically modified mESCs can be selectively differentiated into a homogenous population (>99%) of ATIICs. Importantly, the mESC-derived ATIICs (mESC-ATIICs) exhibited typical lamellar bodies and expressed surfactant protein A, B, and C as normal control ATIICs. When cultured with an air-liquid-interface culture system in Small Airway Epithelial Cell Growth Medium, the mESC-ATIICs can be induced to secrete surfactant proteins after being treated with dibutyryl cAMP+dexamethasone. These mESC-ATIICs can synthesize and secrete surfactant lipid in response to secretagogue, demonstrating active surfactant metabolism in mESC-ATIICs as that seen in normal control ATIICs. In addition, we demonstrated that the selected mESC-ATIICs can be maintained on Matrigel

  2. 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

  3. Role of primary human alveolar epithelial cells in host defense against Francisella tularensis infection.

    Science.gov (United States)

    Gentry, Megan; Taormina, Joanna; Pyles, Richard B; Yeager, Linsey; Kirtley, Michelle; Popov, Vsevolod L; Klimpel, Gary; Eaves-Pyles, Tonyia

    2007-08-01

    Francisella tularensis, an intracellular pathogen, is highly virulent when inhaled. Alveolar epithelial type I (ATI) and type II (ATII) cells line the majority of the alveolar surface and respond to inhaled pathogenic bacteria via cytokine secretion. We hypothesized that these cells contribute to the lung innate immune response to F. tularensis. Results demonstrated that the live vaccine strain (LVS) contacted ATI and ATII cells by 2 h following intranasal inoculation of mice. In culture, primary human ATI or ATII cells, grown on transwell filters, were stimulated on the apical (AP) surface with virulent F. tularensis Schu 4 or LVS. Basolateral (BL) conditioned medium (CM), collected 6 and 24 h later, was added to the BL surfaces of transwell cultures of primary human pulmonary microvasculature endothelial cells (HPMEC) prior to the addition of polymorphonuclear leukocytes (PMNs) or dendritic cells (DCs) to the AP surface. HPMEC responded to S4- or LVS-stimulated ATII, but not ATI, CM as evidenced by PMN and DC migration. Analysis of the AP and BL ATII CM revealed that both F. tularensis strains induced various levels of a variety of cytokines via NF-kappaB activation. ATII cells pretreated with an NF-kappaB inhibitor prior to F. tularensis stimulation substantially decreased interleukin-8 secretion, which did not occur through Toll-like receptor 2, 2/6, 4, or 5 stimulation. These data indicate a crucial role for ATII cells in the innate immune response to F. tularensis. PMID:17502386

  4. Role of Primary Human Alveolar Epithelial Cells in Host Defense against Francisella tularensis Infection▿

    Science.gov (United States)

    Gentry, Megan; Taormina, Joanna; Pyles, Richard B.; Yeager, Linsey; Kirtley, Michelle; Popov, Vsevolod L.; Klimpel, Gary; Eaves-Pyles, Tonyia

    2007-01-01

    Francisella tularensis, an intracellular pathogen, is highly virulent when inhaled. Alveolar epithelial type I (ATI) and type II (ATII) cells line the majority of the alveolar surface and respond to inhaled pathogenic bacteria via cytokine secretion. We hypothesized that these cells contribute to the lung innate immune response to F. tularensis. Results demonstrated that the live vaccine strain (LVS) contacted ATI and ATII cells by 2 h following intranasal inoculation of mice. In culture, primary human ATI or ATII cells, grown on transwell filters, were stimulated on the apical (AP) surface with virulent F. tularensis Schu 4 or LVS. Basolateral (BL) conditioned medium (CM), collected 6 and 24 h later, was added to the BL surfaces of transwell cultures of primary human pulmonary microvasculature endothelial cells (HPMEC) prior to the addition of polymorphonuclear leukocytes (PMNs) or dendritic cells (DCs) to the AP surface. HPMEC responded to S4- or LVS-stimulated ATII, but not ATI, CM as evidenced by PMN and DC migration. Analysis of the AP and BL ATII CM revealed that both F. tularensis strains induced various levels of a variety of cytokines via NF-κB activation. ATII cells pretreated with an NF-κB inhibitor prior to F. tularensis stimulation substantially decreased interleukin-8 secretion, which did not occur through Toll-like receptor 2, 2/6, 4, or 5 stimulation. These data indicate a crucial role for ATII cells in the innate immune response to F. tularensis. PMID:17502386

  5. Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces.

    Science.gov (United States)

    Kaneko, Keita; Togami, Kohei; Yamamoto, Eri; Wang, Shujun; Morimoto, Kazuhiro; Itagaki, Shirou; Chono, Sumio

    2016-10-01

    The distribution characteristics of aerosolized PEGylated liposomes in alveolar epithelial lining fluid (ELF) were examined in rats, and the ensuing mechanisms were investigated in the in vitro uptake and protein adsorption experiments. Nonmodified or PEGylated liposomes (particle size 100 nm) were aerosolized into rat lungs. PEGylated liposomes were distributed more sustainably in ELFs than nonmodified liposomes. Furthermore, the uptake of PEGylated liposomes by alveolar macrophages (AMs) was less than that of nonmodified liposomes. In further in vitro uptake experiments, nonmodified and PEGylated liposomes were opsonized with rat ELF components and then added to NR8383 cells as cultured rat AMs. The uptake of opsonized PEGylated liposomes by NR8383 cells was lower than that of opsonized nonmodified liposomes. Moreover, the protein absorption levels in opsonized PEGylated liposomes were lower than those in opsonized nonmodified liposomes. These findings suggest that sustained distributions of aerosolized PEGylated liposomes in ELFs reflect evasion of liposomal opsonization with surfactant proteins and consequent reductions in uptake by AMs. These data indicate the potential of PEGylated liposomes as aerosol-based drug delivery system that target ELF for the treatment of respiratory diseases. PMID:27334278

  6. Male Sex is Associated with a Reduced Alveolar Epithelial Sodium Transport

    Science.gov (United States)

    Kaltofen, Till; Haase, Melanie; Thome, Ulrich H.; Laube, Mandy

    2015-01-01

    Respiratory distress syndrome (RDS) is the most frequent pulmonary complication in preterm infants. RDS incidence differs between genders, which has been called the male disadvantage. Besides maturation of the surfactant system, Na+ transport driven alveolar fluid clearance is crucial for the prevention of RDS. Na+ transport is mediated by the epithelial Na+ channel (ENaC) and the Na,K-ATPase, therefore potential differences in their expression or activity possibly contribute to the gender imbalance observed in RDS. Fetal distal lung epithelial (FDLE) cells of rat fetuses were separated by sex and analyzed regarding expression and activity of the Na+ transporters. Ussing chamber experiments showed a higher baseline short-circuit current (ISC) and amiloride-sensitive ΔISC in FDLE cells of female origin. In addition, maximal amiloride-sensitive ΔISC and maximal ouabain-sensitive ΔISC of female cells were higher when measured in the presence of a permeabilized basolateral or apical membrane, respectively. The number of FDLE cells per fetus recoverable during cell isolation was also significantly higher in females. In addition, lung wet-to-dry weight ratio was lower in fetal and newborn female pups. Female derived FDLE cells had higher mRNA levels of the ENaC- and Na,K-ATPase subunits. Furthermore, estrogen (ER) and progesterone receptor (PR) mRNA levels were higher in female cells, which might render female cells more responsive, while concentrations of placenta-derived sex steroids do not differ between both genders during fetal life. Inhibition of ER-β abolished the sex differences in Na+ transport and female cells were more responsive to estradiol stimulation. In conclusion, a higher alveolar Na+ transport, possibly attributable to a higher expression of hormone receptors in female FDLE cells, provides an explanation for the well known sex-related difference in RDS occurrence and outcome. PMID:26291531

  7. Male Sex is Associated with a Reduced Alveolar Epithelial Sodium Transport.

    Directory of Open Access Journals (Sweden)

    Till Kaltofen

    Full Text Available Respiratory distress syndrome (RDS is the most frequent pulmonary complication in preterm infants. RDS incidence differs between genders, which has been called the male disadvantage. Besides maturation of the surfactant system, Na+ transport driven alveolar fluid clearance is crucial for the prevention of RDS. Na+ transport is mediated by the epithelial Na+ channel (ENaC and the Na,K-ATPase, therefore potential differences in their expression or activity possibly contribute to the gender imbalance observed in RDS. Fetal distal lung epithelial (FDLE cells of rat fetuses were separated by sex and analyzed regarding expression and activity of the Na+ transporters. Ussing chamber experiments showed a higher baseline short-circuit current (ISC and amiloride-sensitive ΔISC in FDLE cells of female origin. In addition, maximal amiloride-sensitive ΔISC and maximal ouabain-sensitive ΔISC of female cells were higher when measured in the presence of a permeabilized basolateral or apical membrane, respectively. The number of FDLE cells per fetus recoverable during cell isolation was also significantly higher in females. In addition, lung wet-to-dry weight ratio was lower in fetal and newborn female pups. Female derived FDLE cells had higher mRNA levels of the ENaC- and Na,K-ATPase subunits. Furthermore, estrogen (ER and progesterone receptor (PR mRNA levels were higher in female cells, which might render female cells more responsive, while concentrations of placenta-derived sex steroids do not differ between both genders during fetal life. Inhibition of ER-β abolished the sex differences in Na+ transport and female cells were more responsive to estradiol stimulation. In conclusion, a higher alveolar Na+ transport, possibly attributable to a higher expression of hormone receptors in female FDLE cells, provides an explanation for the well known sex-related difference in RDS occurrence and outcome.

  8. Effects of PPARγ ligands on TGF-β1-induced epithelial-mesenchymal transition in alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Dagher Hayat

    2010-02-01

    Full Text Available Abstract Background Transforming growth factor β1 (TGF-β1-mediated epithelial mesenchymal transition (EMT of alveolar epithelial cells (AEC may contribute to lung fibrosis. Since PPARγ ligands have been shown to inhibit fibroblast activation by TGF-β1, we assessed the ability of the thiazolidinediones rosiglitazone (RGZ and ciglitazone (CGZ to regulate TGF-β1-mediated EMT of A549 cells, assessing changes in cell morphology, and expression of cell adhesion molecules E-cadherin (epithelial cell marker and N-cadherin (mesenchymal cell marker, and collagen 1α1 (COL1A1, CTGF and MMP-2 mRNA. Methods Serum-deprived A549 cells (human AEC cell line were pre-incubated with RGZ and CGZ (1 - 30 μM in the absence or presence of the PPARγ antagonist GW9662 (10 μM before TGFβ-1 (0.075-7.5 ng/ml treatment for up to 72 hrs. Changes in E-cadherin, N-cadherin and phosphorylated Smad2 and Smad3 levels were analysed by Western blot, and changes in mRNA levels including COL1A1 assessed by RT-PCR. Results TGFβ-1 (2.5 ng/ml-induced reductions in E-cadherin expression were associated with a loss of epithelial morphology and cell-cell contact. Concomitant increases in N-cadherin, MMP-2, CTGF and COL1A1 were evident in predominantly elongated fibroblast-like cells. Neither RGZ nor CGZ prevented TGFβ1-induced changes in cell morphology, and PPARγ-dependent inhibitory effects of both ligands on changes in E-cadherin were only evident at submaximal TGF-β1 (0.25 ng/ml. However, both RGZ and CGZ inhibited the marked elevation of N-cadherin and COL1A1 induced by TGF-β1 (2.5 ng/ml, with effects on COL1A1 prevented by GW9662. Phosphorylation of Smad2 and Smad3 by TGF-β1 was not inhibited by RGZ or CGZ. Conclusions RGZ and CGZ inhibited profibrotic changes in TGF-β1-stimulated A549 cells independently of inhibition of Smad phosphorylation. Their inhibitory effects on changes in collagen I and E-cadherin, but not N-cadherin or CTGF, appeared to be PPAR

  9. Effects of Pseudomonas aeruginosa elastase on alveolar epithelial permeability in guinea pigs

    International Nuclear Information System (INIS)

    Elastase-deficient mutants of Pseudomonas aeruginosa are less virulent than the wild type and are easily cleared from the lungs of guinea pigs. The effect of P. aeruginosa elastase on lung epithelium, however, is not yet understood. We addressed the hypothesis that breach of the epithelial barrier by elastase from P. aeruginosa allows invading organisms and toxic substances to penetrate the interstitium. We measured the clearance of aerosolized technetium-labeled albumin (molecular weight, 69,000) from the lungs of anesthetized guinea pigs with the aid of a gamma camera and a dedicated computer. Aerosols of the elastase (0.1 to 5 micrograms) increased the rate of clearance of labeled albumin from the lungs in proportion to the elastase dose. Electron microscopic studies using horseradish peroxidase as a tracer revealed that elastase interrupts intercellular tight junctions of the epithelial lining, thereby increasing the permeability to macromolecules. The amounts of elastase used in this report did not cause interstitial or alveolar edema, as determined by both postmortem extravascular lung water volume measurement and morphological examination. The data indicate that the elastase is a potentially important virulence factor in acute lung infection

  10. Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers

    Directory of Open Access Journals (Sweden)

    Fazlollahi F

    2011-11-01

    Full Text Available Farnoosh Fazlollahi1,8, Arnold Sipos1,2, Yong Ho Kim1,2, Sarah F Hamm-Alvarez6, Zea Borok1–3, Kwang-Jin Kim1,2,5–7, Edward D Crandall1,2,4,8 1Will Rogers Institute Pulmonary Research Center, 2Department of Medicine, 3Department of Biochemistry and Molecular Biology, 4Department of Pathology, 5Department of Physiology and Biophysics, 6Department of Pharmacology and Pharmaceutical Sciences, 7Department of Biomedical Engineering, 8Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA Background: In this study, primary rat alveolar epithelial cell monolayers (RAECM were used to investigate transalveolar epithelial quantum dot trafficking rates and underlying transport mechanisms. Methods: Trafficking rates of quantum dots (PEGylated CdSe/ZnS, core size 5.3 nm, hydrodynamic size 25 nm in the apical-to-basolateral direction across RAECM were determined. Changes in bioelectric properties (ie, transmonolayer resistance and equivalent active ion transport rate of RAECM in the presence or absence of quantum dots were measured. Involvement of endocytic pathways in quantum dot trafficking across RAECM was assessed using specific inhibitors (eg, methyl-ß-cyclodextrin, chlorpromazine, and dynasore for caveolin-, clathrin-, and dynamin-mediated endocytosis, respectively. The effects of lowering tight junctional resistance on quantum dot trafficking were determined by depleting Ca2+ in apical and basolateral bathing fluids of RAECM using 2 mM EGTA. Effects of temperature on quantum dot trafficking were studied by lowering temperature from 37°C to 4°C. Results: Apical exposure of RAECM to quantum dots did not elicit changes in transmonolayer resistance or ion transport rate for up to 24 hours; quantum dot trafficking rates were not surface charge-dependent; methyl-ß-cyclodextrin, chlorpromazine, and dynasore did not decrease quantum dot trafficking rates; lowering of temperature

  11. Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Yuen Kit M

    2009-10-01

    Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

  12. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling.

    Science.gov (United States)

    Rock, Jason R; Randell, Scott H; Hogan, Brigid L M

    2010-01-01

    The small airways of the human lung undergo pathological changes in pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), asthma, bronchiolitis obliterans and cystic fibrosis. These clinical problems impose huge personal and societal healthcare burdens. The changes, termed 'pathological airway remodeling', affect the epithelium, the underlying mesenchyme and the reciprocal trophic interactions that occur between these tissues. Most of the normal human airway is lined by a pseudostratified epithelium of ciliated cells, secretory cells and 6-30% basal cells, the proportion of which varies along the proximal-distal axis. Epithelial abnormalities range from hypoplasia (failure to differentiate) to basal- and goblet-cell hyperplasia, squamous- and goblet-cell metaplasia, dysplasia and malignant transformation. Mesenchymal alterations include thickening of the basal lamina, smooth muscle hyperplasia, fibrosis and inflammatory cell accumulation. Paradoxically, given the prevalence and importance of airway remodeling in lung disease, its etiology is poorly understood. This is due, in part, to a lack of basic knowledge of the mechanisms that regulate the differentiation, maintenance and repair of the airway epithelium. Specifically, little is known about the proliferation and differentiation of basal cells, a multipotent stem cell population of the pseudostratified airway epithelium. This Perspective summarizes what we know, and what we need to know, about airway basal cells to evaluate their contributions to normal and abnormal airway remodeling. We contend that exploiting well-described model systems using both human airway epithelial cells and the pseudostratified epithelium of the genetically tractable mouse trachea will enable crucial discoveries regarding the pathogenesis of airway disease. PMID:20699479

  13. The alveolar epithelial differentiation of glandular inner lining cells in a mucoepidermoid carcinoma of the lung: a case report

    Directory of Open Access Journals (Sweden)

    Xu Hong-Tao

    2012-10-01

    Full Text Available Abstract Mucoepidermoid carcinoma is a common malignant epithelial tumor of salivary glands, but relatively rare in lung. The histological features of mucoepidermoid carcinoma of the lung are similar to its counterpart arising from the salivary glands. Here, we reported a special tumor that occurred in the medial segment of the right lower lobe in a 22-year-old man. This tumor exhibited typical features of mucoepidermoid carcinoma with 3 cell types: squamoid cells, mucin-secreting cells and cells of intermediate type. These 3 types of cells organized into cysts, nests, glands and solid patterns. Specially, the inner lining cells of some glandular structures were uniform cuboidal and hobnail-like, similar to the alveolar epithelial cells. Immunohistochemistry staining revealed that the inner lining cells of glandular structures were positive for thyroid transcription factor-1 and surfactant protein-B, used as markers of alveolar epithelial cells, and were negative for p63. These findings for the first time demonstrated a rare alveolar epithelial differentiation of glandular inner lining cells in a mucoepidermoid carcinoma of the lung. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7095988968057804

  14. Protein Expression Profile of Rat Type Two Alveolar Epithelial Cells During Hyperoxic Stress and Recovery

    Science.gov (United States)

    Bhargava, Maneesh

    Rationale: In rodent model systems, the sequential changes in lung morphology resulting from hyperoxic injury are well characterized, and are similar to changes in human acute respiratory distress syndrome (ARDS). In the injured lung, alveolar type two (AT2) epithelial cells play a critical role restoring the normal alveolar structure. Thus characterizing the changes in AT2 cells will provide insights into the mechanisms underpinning the recovery from lung injury. Methods: We applied an unbiased systems level proteomics approach to elucidate molecular mechanisms contributing to lung repair in a rat hyperoxic lung injury model. AT2 cells were isolated from rat lungs at predetermined intervals during hyperoxic injury and recovery. Protein expression profiles were determined by using iTRAQRTM with tandem mass spectrometry. Results: Of 959 distinct proteins identified, 183 significantly changed in abundance during the injury-recovery cycle. Gene Ontology enrichment analysis identified cell cycle, cell differentiation, cell metabolism, ion homeostasis, programmed cell death, ubiquitination, and cell migration to be significantly enriched by these proteins. Gene Set Enrichment Analysis of data acquired during lung repair revealed differential expression of gene sets that control multicellular organismal development, systems development, organ development, and chemical homeostasis. More detailed analysis identified activity in two regulatory pathways, JNK and miR 374. A Short Time-series Expression Miner (STEM) algorithm identified protein clusters with coherent changes during injury and repair. Conclusion: Coherent changes occur in the AT2 cell proteome in response to hyperoxic stress. These findings offer guidance regarding the specific molecular mechanisms governing repair of the injured lung.

  15. Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells

    OpenAIRE

    Kode, Aruna; Yang, Se-Ran; Rahman, Irfan

    2006-01-01

    BACKGROUND:Cigarette smoke mediated oxidative stress and inflammatory events in the airway and alveolar epithelium are important processes in the pathogenesis of smoking related pulmonary diseases. Previously, individual cell lines were used to assess the oxidative and proinflammatory effects of cigarette smoke with confounding results. In this study, a panel of human and rodent transformed epithelial cell lines were used to determine the effects of cigarette smoke extract (CSE) on oxidative ...

  16. Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells

    OpenAIRE

    Rahman Irfan; Yang Se-Ran; Kode Aruna

    2006-01-01

    Abstract Background Cigarette smoke mediated oxidative stress and inflammatory events in the airway and alveolar epithelium are important processes in the pathogenesis of smoking related pulmonary diseases. Previously, individual cell lines were used to assess the oxidative and proinflammatory effects of cigarette smoke with confounding results. In this study, a panel of human and rodent transformed epithelial cell lines were used to determine the effects of cigarette smoke extract (CSE) on o...

  17. Hypoxia inducible factor 3α plays a critical role in alveolarization and distal epithelial cell differentiation during mouse lung development.

    Directory of Open Access Journals (Sweden)

    Yadi Huang

    Full Text Available Lung development occurs under relative hypoxia and the most important oxygen-sensitive response pathway is driven by Hypoxia Inducible Factors (HIF. HIFs are heterodimeric transcription factors of an oxygen-sensitive subunit, HIFα, and a constitutively expressed subunit, HIF1β. HIF1α and HIF2α, encoded by two separate genes, contribute to the activation of hypoxia inducible genes. A third HIFα gene, HIF3α, is subject to alternative promoter usage and splicing, leading to three major isoforms, HIF3α, NEPAS and IPAS. HIF3α gene products add to the complexity of the hypoxia response as they function as dominant negative inhibitors (IPAS or weak transcriptional activators (HIF3α/NEPAS. Previously, we and others have shown the importance of the Hif1α and Hif2α factors in lung development, and here we investigated the role of Hif3α during pulmonary development. Therefore, HIF3α was conditionally expressed in airway epithelial cells during gestation and although HIF3α transgenic mice were born alive and appeared normal, their lungs showed clear abnormalities, including a post-pseudoglandular branching defect and a decreased number of alveoli. The HIF3α expressing lungs displayed reduced numbers of Clara cells, alveolar epithelial type I and type II cells. As a result of HIF3α expression, the level of Hif2α was reduced, but that of Hif1α was not affected. Two regulatory genes, Rarβ, involved in alveologenesis, and Foxp2, a transcriptional repressor of the Clara cell specific Ccsp gene, were significantly upregulated in the HIF3α expressing lungs. In addition, aberrant basal cells were observed distally as determined by the expression of Sox2 and p63. We show that Hif3α binds a conserved HRE site in the Sox2 promoter and weakly transactivated a reporter construct containing the Sox2 promoter region. Moreover, Hif3α affected the expression of genes not typically involved in the hypoxia response, providing evidence for a novel

  18. Breakdown of Epithelial Barrier Integrity and Overdrive Activation of Alveolar Epithelial Cells in the Pathogenesis of Acute Respiratory Distress Syndrome and Lung Fibrosis

    Directory of Open Access Journals (Sweden)

    Shigehisa Yanagi

    2015-01-01

    Full Text Available Individual alveolar epithelial cells (AECs collaboratively form a tight barrier between atmosphere and fluid-filled tissue to enable normal gas exchange. The tight junctions of AECs provide intercellular sealing and are integral to the maintenance of the AEC barrier integrity. Disruption and failure of reconstitution of AEC barrier result in catastrophic consequences, leading to alveolar flooding and subsequent devastating fibrotic scarring. Recent evidences reveal that many of the fibrotic lung diseases involve AECs both as a frequent target of injury and as a driver of ongoing pathological processes. Aberrantly activated AECs express most of the growth factors and chemokines responsible for the proliferation, migration, and activation of fibroblasts. Current evidences suggest that AECs may acquire overdrive activation in the initial step of fibrosis by several mechanisms, including abnormal recapitulation of the developmental pathway, defects of the molecules essential for epithelial integrity, and acceleration of aging-related properties. Among these initial triggering events, epithelial Pten, a multiple phosphatase that negatively regulates the PI3K/Akt pathway and is crucial for lung development, is essential for the prevention of alveolar flooding and lung fibrosis through the regulation of AEC barrier integrity after injury. Reestablishment of AEC barrier integrity also involves the deployment of specialized stem/progenitor cells.

  19. Autophagy protects type II alveolar epithelial cells from Mycobacterium tuberculosis infection

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xu-Guang [Center for Clinical Laboratory Medicine of PLA, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Department of Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Ji, Tian-Xing [Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Xia, Yong, E-mail: gysyxy@gmail.com [Center for Clinical Laboratory Medicine of PLA, Xijing Hospital, Fourth Military Medical University, Xi' an (China); Ma, Yue-Yun, E-mail: cmbmayy@fmmu.edu.cn [Center for Clinical Laboratory Medicine of PLA, Xijing Hospital, Fourth Military Medical University, Xi' an (China)

    2013-03-08

    Highlights: ► We investigated the protective effect of autophagy pathway against MTB infection. ► MTB-infected A549 cells had higher LDH release. ► Inhibition of autophagy signaling significantly enhanced the MTB-induced necrosis. ► Autophagy prevents apoptosis and promotes cell survival in infected cells. -- Abstract: This study was designed to investigate the protective effect of the autophagy signaling pathway against Mycobacterium tuberculosis infection in type II alveolar epithelial cells. An in vitro M. tuberculosis system was established using human A549 cells. Infection-induced changes in the expression of the autophagic marker LC3 were assessed by reverse transcription-PCR and Western blotting. Morphological changes in autophagosomes were detected by transmission electron microscopy (TEM). The function of the autophagy signaling pathway during infection was assessed by measuring the level of cell death and the amount of lactate dehydrogenase (LDH) released in the presence or absence of the inhibitor 3-methyladenine (3-MA). In addition, effects on LDH release were assessed after the siRNA-mediated knockdown of the essential autophagosomal structural membrane protein Atg5. LC3 mRNA expression was significantly reduced in M.tuberculosis-infected A549 cells (16888.76 ± 1576.34 vs. uninfected: 12744.29 ± 1089.37; P < 0.05). TEM revealed M.tuberculosis bacilli-containing compartments that were surrounded by double membranes characteristic of the autophagic process. M.tuberculosis-infected A549 cells released more LDH (1.45 ± 0.12 vs. uninfected: 0.45 ± 0.04; P < 0.05). The inhibition of autophagy signaling significantly enhanced M.tuberculosis-induced necrosis (3-MA: 75 ± 5% vs. untreated: 15 ± 1%; P < 0.05) and LDH release (3-MA: 2.50 ± 0.24 vs. untreated: 0.45 ± 0.04; Atg5 knockdown: 3.19 ± 0.29 vs. untreated: 1.28 ± 0.11; P < 0.05). Our results indicate that autophagy signaling pathway prevents apoptosis in type II alveolar epithelial cells

  20. Autophagy protects type II alveolar epithelial cells from Mycobacterium tuberculosis infection

    International Nuclear Information System (INIS)

    Highlights: ► We investigated the protective effect of autophagy pathway against MTB infection. ► MTB-infected A549 cells had higher LDH release. ► Inhibition of autophagy signaling significantly enhanced the MTB-induced necrosis. ► Autophagy prevents apoptosis and promotes cell survival in infected cells. -- Abstract: This study was designed to investigate the protective effect of the autophagy signaling pathway against Mycobacterium tuberculosis infection in type II alveolar epithelial cells. An in vitro M. tuberculosis system was established using human A549 cells. Infection-induced changes in the expression of the autophagic marker LC3 were assessed by reverse transcription-PCR and Western blotting. Morphological changes in autophagosomes were detected by transmission electron microscopy (TEM). The function of the autophagy signaling pathway during infection was assessed by measuring the level of cell death and the amount of lactate dehydrogenase (LDH) released in the presence or absence of the inhibitor 3-methyladenine (3-MA). In addition, effects on LDH release were assessed after the siRNA-mediated knockdown of the essential autophagosomal structural membrane protein Atg5. LC3 mRNA expression was significantly reduced in M.tuberculosis-infected A549 cells (16888.76 ± 1576.34 vs. uninfected: 12744.29 ± 1089.37; P < 0.05). TEM revealed M.tuberculosis bacilli-containing compartments that were surrounded by double membranes characteristic of the autophagic process. M.tuberculosis-infected A549 cells released more LDH (1.45 ± 0.12 vs. uninfected: 0.45 ± 0.04; P < 0.05). The inhibition of autophagy signaling significantly enhanced M.tuberculosis-induced necrosis (3-MA: 75 ± 5% vs. untreated: 15 ± 1%; P < 0.05) and LDH release (3-MA: 2.50 ± 0.24 vs. untreated: 0.45 ± 0.04; Atg5 knockdown: 3.19 ± 0.29 vs. untreated: 1.28 ± 0.11; P < 0.05). Our results indicate that autophagy signaling pathway prevents apoptosis in type II alveolar epithelial cells

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

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    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.

  2. Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias

    OpenAIRE

    Kajiki Akira; Fukushima Kazuo; Kawabata Masaharu; Wakamatsu Kentaro; Kitasato Yasuhiko; Nagata Nobuhiko; Kitahara Yoshinari; Watanabe Kentaro

    2011-01-01

    Abstract Background It is difficult to predict survival in patients with idiopathic pulmonary fibrosis. Recently, several proteins, such as surfactant protein (SP) and KL-6, have been reported to be useful biologic markers for prediction of prognosis for interstitial pneumonias. It is not clear whether there is any relationship between expression of these proteins in regenerative/hyperplastic alveolar epithelial cells and prognosis of idiopathic interstitial pneumonias (IIPs). Objectives This...

  3. Prognostic value of immunohistochemical surfactant protein A expression in regenerative/hyperplastic alveolar epithelial cells in idiopathic interstitial pneumonias

    OpenAIRE

    Nagata, Nobuhiko; Kitasato, Yasuhiko; Wakamatsu, Kentaro; Kawabata, Masaharu; Fukushima, Kazuo; Kajiki, Akira; Kitahara, Yoshinari; Watanabe, Kentaro

    2011-01-01

    Background It is difficult to predict survival in patients with idiopathic pulmonary fibrosis. Recently, several proteins, such as surfactant protein (SP) and KL-6, have been reported to be useful biologic markers for prediction of prognosis for interstitial pneumonias. It is not clear whether there is any relationship between expression of these proteins in regenerative/hyperplastic alveolar epithelial cells and prognosis of idiopathic interstitial pneumonias (IIPs). Objectives This study ai...

  4. Regulation of alveolar procoagulant activity and permeability in direct acute lung injury by lung epithelial tissue factor.

    Science.gov (United States)

    Shaver, Ciara M; Grove, Brandon S; Putz, Nathan D; Clune, Jennifer K; Lawson, William E; Carnahan, Robert H; Mackman, Nigel; Ware, Lorraine B; Bastarache, Julie A

    2015-11-01

    Tissue factor (TF) initiates the extrinsic coagulation cascade in response to tissue injury, leading to local fibrin deposition. Low levels of TF in mice are associated with increased severity of acute lung injury (ALI) after intratracheal LPS administration. However, the cellular sources of the TF required for protection from LPS-induced ALI remain unknown. In the current study, transgenic mice with cell-specific deletions of TF in the lung epithelium or myeloid cells were treated with intratracheal LPS to determine the cellular sources of TF important in direct ALI. Cell-specific deletion of TF in the lung epithelium reduced total lung TF expression to 39% of wild-type (WT) levels at baseline and to 29% of WT levels after intratracheal LPS. In contrast, there was no reduction of TF with myeloid cell TF deletion. Mice lacking myeloid cell TF did not differ from WT mice in coagulation, inflammation, permeability, or hemorrhage. However, mice lacking lung epithelial TF had increased tissue injury, impaired activation of coagulation in the airspace, disrupted alveolar permeability, and increased alveolar hemorrhage after intratracheal LPS. Deletion of epithelial TF did not affect alveolar permeability in an indirect model of ALI caused by systemic LPS infusion. These studies demonstrate that the lung epithelium is the primary source of TF in the lung, contributing 60-70% of total lung TF, and that lung epithelial, but not myeloid, TF may be protective in direct ALI. PMID:25884207

  5. Human Vγ9Vδ2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells

    Science.gov (United States)

    Li, Hong; Xiang, Zheng; Feng, Ting; Li, Jinrong; Liu, Yinping; Fan, Yingying; Lu, Qiao; Yin, Zhongwei; Yu, Meixing; Shen, Chongyang; Tu, Wenwei

    2013-01-01

    γδ-T cells play an indispensable role in host defense against different viruses, including influenza A virus. However, whether these cells have cytotoxic activity against influenza virus-infected lung alveolar epithelial cells and subsequently contribute to virus clearance remains unknown. Using influenza virus-infected A549 cells, human lung alveolar epithelial cells, we investigated the cytotoxic activity of aminobisphosphonate pamidronate (PAM)-expanded human Vγ9Vδ2-T cells and their underlying mechanisms. We found that PAM could selectively activate and expand human Vγ9Vδ2-T cells. PAM-expanded human Vγ9Vδ2-T cells efficiently killed influenza virus-infected lung alveolar epithelial cells and inhibited virus replication. The cytotoxic activity of PAM-expanded Vγ9Vδ2-T cells was dependent on cell-to-cell contact and required NKG2D activation. Perforin–granzyme B, tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas–Fas ligand (FasL) pathways were involved in their cytotoxicity. Our study suggests that targeting γδ-T cells by PAM can potentially offer an alternative option for the treatment of influenza virus. PMID:23353835

  6. Incorporation of tritiated thymidine by epithelial and interstitial cells in bronchiolar-alveolar regions of asbestos-exposed rats

    International Nuclear Information System (INIS)

    Inhaled asbestos causes progressive interstitial lung disease. The authors have performed a series of studies to elucidate early pathogenetic events at sites of fiber deposition in asbestos-exposed rats. This study reports that a single 5-hour exposure to chrysotile asbestos induces significant increases in incorporation of tritiated thymidine (3HTdR) into nuclei of epithelial and interstitial cells of bronchiolar-alveolar regions. No cell populations in air-exposed or carbonyl iron-exposed control animals exhibited more than 1% labeling at any point in time. Immediately after the 5-hour asbestos exposure, incorporation was normal. By 19 hours after exposure there was a significant increase in incorporation of 3HTdR, particularly by Type II epithelial cells of the first alveolar duct bifurcations. The greatest increase in degree of incorporation (up to 18-fold) was observed 24 hours after exposure, and increased percentages of 3HTdR-labeled cells were maintained through the 48 hours postexposure period. Normal labeling was present by 8 days after exposure, and this level remained through the 1-month period studied. This apparent mitogenic response correlates with increased numbers of bronchiolar-alveolar epithelial and interstitial cells demonstrated by ultrastructural morphometry in correlative studies. The authors speculate that the incorporation of 3HTdR could be induced by the direct effects of inhaled fibers or by mitogenic factors released from macrophages attracted to the inhaled asbestos

  7. Effect of P2X7 receptor knockout on AQP-5 expression of type I alveolar epithelial cells.

    Directory of Open Access Journals (Sweden)

    Georg Ebeling

    Full Text Available P2X7 receptors, ATP-gated cation channels, are specifically expressed in alveolar epithelial cells. The pathophysiological function of this lung cell type, except a recently reported putative involvement in surfactant secretion, is unknown. In addition, P2X7 receptor-deficient mice show reduced inflammation and lung fibrosis after exposure with bleomycin. To elucidate the role of the P2X7 receptor in alveolar epithelial type I cells we characterized the pulmonary phenotype of P2X7 receptor knockout mice by using immunohistochemistry, western blot analysis and real-time RT PCR. No pathomorphological signs of fibrosis were found. Results revealed, however, a remarkable loss of aquaporin-5 protein and mRNA in young knockout animals. Additional in vitro experiments with bleomycin treated precision cut lung slices showed a greater sensitivity of the P2X7 receptor knockout mice in terms of aquaporin-5 reduction as wild type animals. Finally, P2X7 receptor function was examined by using the alveolar epithelial cell lines E10 and MLE-12 for stimulation experiments with bleomycin. The in vitro activation of P2X7 receptor was connected with an increase of aquaporin-5, whereas the inhibition of the receptor with oxidized ATP resulted in down regulation of aquaporin-5. The early loss of aquaporin-5 which can be found in different pulmonary fibrosis models does not implicate a specific pathogenetic role during fibrogenesis.

  8. Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones

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    Hiroshi Kondo

    2015-01-01

    Full Text Available Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated an in vitro system to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12 were further analyzed. Under serum-free culture conditions, surfactant protein C (SPC, an ATII marker, was upregulated in both H12 and B7. Aquaporin 5 (AQP5, an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited, SPC and thyroid transcription factor-1 (TTF-1 expression levels were enhanced. After treatment with dexamethasone (DEX, 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP, 3-isobutyl-1-methylxanthine (IBMX, and keratinocyte growth factor (KGF, surfactant protein B and TTF-1 expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.

  9. The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis

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    Seok-Jo Kim

    2015-09-01

    Full Text Available Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC programmed cell death (apoptosis that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF and asbestosis (pulmonary fibrosis following asbestos exposure. The mammalian mitochondrial DNA (mtDNA encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidence implicating that oxidative stress-induced mtDNA damage promotes AEC apoptosis and pulmonary fibrosis. We focus on the emerging role for AEC mtDNA damage repair by 8-oxoguanine DNA glycosylase (OGG1 and mitochondrial aconitase (ACO-2 in maintaining mtDNA integrity which is important in preventing AEC apoptosis and asbestos-induced pulmonary fibrosis in a murine model. We then review recent studies linking the sirtuin (SIRT family members, especially SIRT3, to mitochondrial integrity and mtDNA damage repair and aging. We present a conceptual model of how SIRTs modulate reactive oxygen species (ROS-driven mitochondrial metabolism that may be important for their tumor suppressor function. The emerging insights into the pathobiology underlying AEC mtDNA damage and apoptosis is suggesting novel therapeutic targets that may prove useful for the management of age-related diseases, including pulmonary fibrosis and lung cancer.

  10. Expression of p75NGFR, a Proliferative and Basal Cell Marker, in the Buccal Mucosa Epithelium during Re-epithelialization

    International Nuclear Information System (INIS)

    We investigated the expression of p75NGFR, a proliferative and basal cell marker, in the mouse buccal mucosa epithelium during wound healing in order to elucidate the role of epithelial stem cells. Epithelial defects were generated in the epithelium of the buccal mucosa of 6-week-old mice using CO2 laser irradiation. BrdU was immediately administered to mice following laser irradiation. They were then sacrificed after 1, 3, 7, and 14 days. Paraffin sections were prepared and the irradiated areas were analyzed using immunohistochemistry with anti-p75NGFR, BrdU, PCNA, and CK14 antibodies. During re-epithelialization, PCNA (–)/p75NGFR (+) cells extended to the wound, which then closed, whereas PCNA (+)/p75NGFR (+) cells were not observed at the edge of the wound. In addition, p75NGFR (–)/CK14 (+), which reflected the presence of post-mitotic differentiating cells, was observed in the supra-basal layers of the extended epithelium. BrdU (+)/p75NGFR (+), which reflected the presence of epithelial stem cells, was detected sparsely in buccal basal epithelial cells after healing, and disappeared after 7 days. These results suggest that p75NGFR (+) keratinocytes are localized in the basal layer, which contains oral epithelial stem cells, and retain the ability to proliferate in order to regenerate the buccal mucosal epithelium

  11. Transforming Growth Factor β1 Inhibits Cystic Fibrosis Transmembrane Conductance Regulator-dependent cAMP-stimulated Alveolar Epithelial Fluid Transport via a Phosphatidylinositol 3-Kinase-dependent Mechanism*

    OpenAIRE

    Roux, Jérémie; Carles, Michel; Koh, Hidefumi; Goolaerts, Arnaud; Ganter, Michael T.; Chesebro, Brian B; Howard, Marybeth; Houseman, Benjamin T.; Finkbeiner, Walter; Shokat, Kevan M.; Paquet, Agnès C.; Matthay, Michael A; Pittet, Jean-François

    2009-01-01

    Exogenous or endogenous β2-adrenergic receptor agonists enhance alveolar epithelial fluid transport via a cAMP-dependent mechanism that protects the lungs from alveolar flooding in acute lung injury. However, impaired alveolar fluid clearance is present in most of the patients with acute lung injury and is associated with increased mortality, although the mechanisms responsible for this inhibition of the alveolar epithelial fluid transport are not completely understood. Here, we found that tr...

  12. Detection of alveolar epithelial injury by 99mTc-DTPA radioaerosol inhalation lung scan following blunt chest trauma

    International Nuclear Information System (INIS)

    DTPA clearance rate is a reliable index of alveolar epithelial permeability, and is a highly sensitive marker of pulmonary epithelial damage, even of mild degree. In this study, 99mTc-DTPA aerosol inhalation scintigraphy was used to assess the pulmonary epithelial membrane permeability and to investigate the possible application of this permeability value as an indicator of early alveolar or interstitial changes in patients with blunt chest trauma. A total of 26 patients was chest trauma (4 female, 22 male, 31-80 yrs, mean age; 53±13 yrs) who were referred to the emergency department in our hospital participated in this study. Technetium-99m diethylene triamine pentaacetic acid (DTPA) aerosol inhalation scintigraphy was performed on the first and thirtieth days after trauma. Clearance half times (T1/2) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. On the first day, mean T1/2 value of the whole lung was 63±19 minutes (min), and thirtieth day mean T1/2 value was 67±21 min. On the first day, mean PI values of the lung and 30th day mean PI value were 0.60±0.05, and 0.63 ±0.05, respectively. Significant changes were observed in radioaerosol clearance and penetration indices. Following chest trauma, clearance of 99mTc-DTPA increased owing to breakdown of the alveolar-capillary barrier. This increase in the epithelial permeability of the lung appears to be an early manifestation of lung disease that may lead to efficient therapy in the early phase. (author)

  13. The vitronectin RGD motif regulates TGF-β-induced alveolar epithelial cell apoptosis.

    Science.gov (United States)

    Wheaton, Amanda K; Velikoff, Miranda; Agarwal, Manisha; Loo, Tiffany T; Horowitz, Jeffrey C; Sisson, Thomas H; Kim, Kevin K

    2016-06-01

    Transforming growth factor-β (TGF-β) is a critical driver of acute lung injury and fibrosis. Injury leads to activation of TGF-β, which regulates changes in the cellular and matrix makeup of the lung during the repair and fibrosis phase. TGF-β can also initiate alveolar epithelial cell (AEC) apoptosis. Injury leads to destruction of the laminin-rich basement membrane, which is replaced by a provisional matrix composed of arginine-glycine-aspartate (RGD) motif-containing plasma matrix proteins, including vitronectin and fibronectin. To determine the role of specific matrix proteins on TGF-β-induced apoptosis, we studied primary AECs cultured on different matrix conditions and utilized mice with deletion of vitronectin (Vtn(-/-)) or mice in which the vitronectin RGD motif is mutated to nonintegrin-binding arginine-glycine-glutamate (RGE) (Vtn(RGE/RGE)). We found that AECs cultured on fibronectin and vitronectin or in wild-type mouse serum are resistant to TGF-β-induced apoptosis. In contrast, AECs cultured on laminin or in serum from Vtn(-/-) or Vtn(RGE/RGE) mice undergo robust TGF-β-induced apoptosis. Plasminogen activator inhibitor-1 (PAI-1) sensitizes AECs to greater apoptosis by disrupting AEC engagement to vitronectin. Inhibition of integrin-associated signaling proteins augments AEC apoptosis. Mice with transgenic deletion of PAI-1 have less apoptosis after bleomycin, but deletion of vitronectin or disruption of the vitronectin RGD motif reverses this protection, suggesting that the proapoptotic function of PAI-1 is mediated through vitronectin inhibition. Collectively, these data suggest that integrin-matrix signaling is an important regulator of TGF-β-mediated AEC apoptosis and that PAI-1 functions as a natural regulator of this interaction. PMID:27106291

  14. Shape matters: effects of silver nanospheres and wires on human alveolar epithelial cells

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    Stoehr Linda C

    2011-12-01

    Full Text Available Abstract Background In nanotoxicology, the exact role of particle shape, in relation to the composition, on the capacity to induce toxicity is largely unknown. We investigated the toxic and immunotoxic effects of silver wires (length: 1.5 - 25 μm; diameter 100 - 160 nm, spherical silver nanoparticles (30 nm and silver microparticles ( Methods Wires and nanoparticles were synthesized by wet-chemistry methods and extensively characterized. Cell viability and cytotoxicity were assessed and potential immunotoxic effects were investigated. To compare the effects on an activated and a resting immune system, cells were stimulated with rhTNF-α or left untreated. Changes in intracellular free calcium levels were determined using calcium imaging. Finally, ion release from the particles was assessed by ICP-MS and the effects of released ions on cell viability and cytotoxicity were tested. Results No effects were observed for the spherical particles, whereas the silver wires significantly reduced cell viability and increased LDH release from A549 cells. Cytokine promoter induction and NF-κB activation decreased in a concentration dependent manner similar to the decrease seen in cell viability. In addition, a strong increase of intracellular calcium levels within minutes after addition of wires was observed. This toxicity was not due to free silver ions, since the samples with the highest ion release did not induce toxicity and ion release control experiments with cells treated with pre-incubated medium did not show any effects either. Conclusions These data showed that silver wires strongly affect the alveolar epithelial cells, whereas spherical silver particles had no effect. This supports the hypothesis that shape is one of the important factors that determine particle toxicity.

  15. Reactive oxygen species initiate luminal but not basal cell death in cultured human mammary alveolar structures: a potential regulator of involution

    OpenAIRE

    Thomas, E; Zeps, N.; Rigby, P; Hartmann, P

    2011-01-01

    Post-lactational involution of the mammary gland is initiated within days of weaning. Clearing of cells occurs by apoptosis of the milk-secreting luminal cells in the alveoli and through stromal tissue remodeling to return the gland almost completely to its pre-pregnant state. The pathways that specifically target involution of the luminal cells in the alveoli but not the basal and ductal cells are poorly understood. In this study we show in cultured human mammary alveolar structures that the...

  16. Linking progression of fibrotic lung remodeling and ultrastructural alterations of alveolar epithelial type II cells in the amiodarone mouse model.

    Science.gov (United States)

    Birkelbach, Bastian; Lutz, Dennis; Ruppert, Clemens; Henneke, Ingrid; Lopez-Rodriguez, Elena; Günther, Andreas; Ochs, Matthias; Mahavadi, Poornima; Knudsen, Lars

    2015-07-01

    Chronic injury of alveolar epithelial type II cells (AE2 cells) represents a key event in the development of lung fibrosis in animal models and in humans, such as idiopathic pulmonary fibrosis (IPF). Intratracheal delivery of amiodarone to mice results in a profound injury and macroautophagy-dependent apoptosis of AE2 cells. Increased autophagy manifested in AE2 cells by disturbances of the intracellular surfactant. Hence, we hypothesized that ultrastructural alterations of the intracellular surfactant pool are signs of epithelial stress correlating with the severity of fibrotic remodeling. With the use of design-based stereology, the amiodarone model of pulmonary fibrosis in mice was characterized at the light and ultrastructural level during progression. Mean volume of AE2 cells, volume of lamellar bodies per AE2 cell, and mean size of lamellar bodies were correlated to structural parameters reflecting severity of fibrosis like collagen content. Within 2 wk amiodarone leads to an increase in septal wall thickness and a decrease in alveolar numbers due to irreversible alveolar collapse associated with alveolar surfactant dysfunction. Progressive hypertrophy of AE2 cells and increase in mean individual size and total volume of lamellar bodies per AE2 cell were observed. A high positive correlation of these AE2 cell-related ultrastructural changes and the deposition of collagen fibrils within septal walls were established. Qualitatively, similar alterations could be found in IPF samples with mild to moderate fibrosis. We conclude that ultrastructural alterations of AE2 cells including the surfactant system are tightly correlated with the progression of fibrotic remodeling. PMID:25957292

  17. Computer simulation of wound closure in epithelial tissues: Cell-basal-lamina adhesion

    Science.gov (United States)

    Nagai, Tatsuzo; Honda, Hisao

    2009-12-01

    The mechanism of wound closure in epithelial tissues, i.e., cell monolayer sheets, is investigated through computer simulations. A wound means an area in which some cells have been removed from the normal tissue. The vertex dynamics cell model [T. Nagai and H. Honda, Philos. Mag. B 81, 699 (2001)], which describes morphogenesis of epithelial tissues using the concepts of statistical physics, is modified and applied to the closure of small wounds without mitosis. It is shown that cell-basal-lamina adhesion governs the wound closure competing with cell-cell adhesion and cell elasticity. The simulation results reproduce the actual wound closure process qualitatively and partly quantitatively. The closing proceeds with the translation of the edges of wound polygons toward the wound center and the intermittent reduction in the number of polygon edges. Over time, the process leads to an exponential decrease in the wound area. A shape factor is introduced to describe the wound shape quantitatively and is used to examine the time variation thereof. A method for determining model parameters by comparison with the experiments is given.

  18. Epithelial basal cells are distinct from dendritic cells and macrophages in the mouse epididymis.

    Science.gov (United States)

    Shum, Winnie W; Smith, Tegan B; Cortez-Retamozo, Virna; Grigoryeva, Lubov S; Roy, Jeremy W; Hill, Eric; Pittet, Mikael J; Breton, Sylvie; Da Silva, Nicolas

    2014-05-01

    The epithelium that lines the epididymal duct establishes the optimal milieu in which spermatozoa mature, acquire motility, and are stored. This finely tuned environment also protects antigenic sperm against pathogens and autoimmunity, which are potential causes of transient or permanent infertility. The epididymal epithelium is pseudostratified and contains basal cells (BCs) that are located beneath other epithelial cells. Previous studies showed that in the mouse epididymis, BCs possess macrophage-like characteristics. However, we previously identified a dense population of cells belonging to the mononuclear phagocyte (MP) system (comprised of macrophages and dendritic cells) in the basal compartment of the mouse epididymis and showed that a subset of MPs express the macrophage marker F4/80. In the present study, we evaluate the distribution of BCs and MPs in the epididymis of transgenic CD11c-EYFP mice, in which EYFP is expressed exclusively in MPs, using antibodies against the BC marker keratin 5 (KRT5) and the macrophage marker F4/80. Immunofluorescence labeling for laminin, a basement membrane marker, showed that BCs and most MPs are located in the basal region of the epithelium. Confocal microscopy showed that in the initial segment, both BCs and MPs project intraepithelial extensions and establish a very intricate network. Flow cytometry experiments demonstrated that epididymal MPs and BCs are phenotypically distinct. BCs do not express F4/80, and MPs do not express KRT5. Therefore, despite their proximity and some morphological similarities with peritubular macrophages and dendritic cells, BCs do not belong to the MP system. PMID:24648397

  19. Construction of p66Shc gene interfering lentivirus vectors and its effects on alveolar epithelial cells apoptosis induced by hyperoxia

    Science.gov (United States)

    Zhang, Chan; Dong, Wen-Bin; Zhao, Shuai; Li, Qing-Ping; Kang, Lan; Lei, Xiao-Ping; Guo, Lin; Zhai, Xue-Song

    2016-01-01

    Background The aim of this study is to observe the inhibitive effects of p66Shc gene interfering lentivirus vectors on the expression of p66Shc, and to explore its effects on alveolar epithelial cells apoptosis induced by hyperoxia. Methods The gene sequences were cloned into the pLenR-GPH-shRNA lentiviral vector, which was selected by Genebank searches. The pLenR-GPH-shRNA and lentiviral vector packaging plasmid mix were cotransfected into 293T cells to package lentiviral particles. Culture virus supernatant was harvested, and then the virus titer was determined by serial dilution assay. A549 cells were transduced with the constructed lentiviral vectors, and real-time polymerase chain reaction (RT-PCR) and Western blot were used to evaluate p66Shc expression. This study is divided into a control group, a hyperoxia group, an A549-p66ShcshRNA hyperoxia group, and a negative lentivirus group. Cell apoptosis was detected by flow cytometry after 24 hours; the expression of X-linked inhibitor of apoptosis protein (XIAP) and caspase-9 were detected by immunohistochemistry assay. The production of reactive oxygen species and cellular mitochondria membrane potential (ΔΨm) were determined by fluorescence microscopy. Results We successfully established the p66Shc gene interfering lentivirus vectors, A549-p66ShcshRNA. The A549-p66ShcshRNA was transfected into alveolar epithelial cells, and the inhibitive effects on the expression of p66Shc were observed. Both RT-PCR and Western blot demonstrated downregulation of p66Shc expression in A549 cells. In the A549-p66ShcshRNA hyperoxia group, we found dampened oxidative stress. A549-p66ShcshRNA can cause p66Shc gene silencing, reduce mitochondrial reactive oxygen species generation, reduce membrane potential decrease, reduce the apoptosis of A549 cells, and reduce alveolar epithelial cell injury, while the lentiviral empty vector group had no such changes. Conclusion p66Shc gene interfering lentivirus vector can affect the

  20. Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells

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    Rahman Irfan

    2006-10-01

    Full Text Available Abstract Background Cigarette smoke mediated oxidative stress and inflammatory events in the airway and alveolar epithelium are important processes in the pathogenesis of smoking related pulmonary diseases. Previously, individual cell lines were used to assess the oxidative and proinflammatory effects of cigarette smoke with confounding results. In this study, a panel of human and rodent transformed epithelial cell lines were used to determine the effects of cigarette smoke extract (CSE on oxidative stress markers, cell toxicity and proinflammatory cytokine release and compared the effects with that of primary human small airway epithelial cells (SAEC. Methods Primary human SAEC, transformed human (A549, H1299, H441, and rodent (murine MLE-15, rat L2 alveolar epithelial cells were treated with different concentrations of CSE (0.2–10% ranging from 20 min to 24 hr. Cytotoxicity was assessed by lactate dehydrogenase release assay, trypan blue exclusion method and double staining with acridine orange and ethidium bromide. Glutathione concentration was measured by enzymatic recycling assay and 4-hydroxy-2-nonenal levels by using lipid peroxidation assay kit. The levels of proinflammatory cytokines (e.g. IL-8 and IL-6 were measured by ELISA. Nuclear translocation of the transcription factor, NF-κB was assessed by immunocytochemistry and immunoblotting. Results Cigarette smoke extract dose-dependently depleted glutathione concentration, increased 4-hydroxy-2-nonenal (4-HNE levels, and caused necrosis in the transformed cell lines as well as in SAEC. None of the transformed cell lines showed any significant release of cytokines in response to CSE. CSE, however, induced IL-8 and IL-6 release in primary cell lines in a dose-dependent manner, which was associated with the nuclear translocation of NF-κB in SAEC. Conclusion This study suggests that primary, but not transformed, lung epithelial cells are an appropriate model to study the inflammatory

  1. 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

  2. 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

  3. The influence of volatile anesthetics on alveolar epithelial permeability measured by noninvasive radionuclide lung scan

    International Nuclear Information System (INIS)

    Many volatile anesthetics have long been thought to affect pulmonary functions including lung ventilation (LV) and alveolar epithelial permeability (AEP). The purpose of this study is to examine the influence of volatile anesthetics on LV and AEP by noninvasive radionuclide lung imaging of technetium-99m labeled diethylene triamine pentaacetic acid radioaerosol inhalation lung scan (DTPA lung scan). Twenty patients undergoing surgery and receiving volatile anesthesia with 1% halothane were enrolled as the study group 1. The other 20 patients undergoing surgery and receiving volatile anesthesia with 1.5% isoflurane were enrolled as the study group 2. At the same time, 20 patients undergoing surgery with intravenous anesthesia drugs were included as a control group. Before surgery, 1 hour after surgery, and 1 week after surgery, we investigated the 3 groups of patients with DTPA lung scan to evaluate LV and AEP by 99mTc DTPA clearance halftime (T1/2). No significant change or abnormality of LV before surgery, 1 hour after surgery, or 1 week after surgery was found among the 3 groups of patients. In the control group, the 99mTc DTPA clearance T1/2 was 63.5±16.4, 63.1±18.4, and 62.8±17.0 minutes, before surgery, 1 hour after surgery, and 1 week after surgery, respectively. In group 1, it was 65.9±9.3, 62.5±9.1, and 65.8±10.3 minutes, respectively. No significant change in AEP before surgery, 1 hour after surgery, or 1 week after surgery was found. However, in group 2, the99mTc DTPA clearance T1/2 was 65.5±13.2, 44.9±10.5, and 66.1±14.0 minutes, respectively. A significant transient change in AEP was found 1 hour after surgery, but it recovered 1 week after surgery. We conclude that volatile anesthesia is safe for LV and AEP, and only isoflurane can induce transient change of AEP. (author)

  4. Interactions of Francisella tularensis with Alveolar Type II Epithelial Cells and the Murine Respiratory Epithelium.

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    Matthew Faron

    Full Text Available Francisella tularensis is classified as a Tier 1 select agent by the CDC due to its low infectious dose and the possibility that the organism can be used as a bioweapon. The low dose of infection suggests that Francisella is unusually efficient at evading host defenses. Although ~50 cfu are necessary to cause human respiratory infection, the early interactions of virulent Francisella with the lung environment are not well understood. To provide additional insights into these interactions during early Francisella infection of mice, we performed TEM analysis on mouse lungs infected with F. tularensis strains Schu S4, LVS and the O-antigen mutant Schu S4 waaY::TrgTn. For all three strains, the majority of the bacteria that we could detect were observed within alveolar type II epithelial cells at 16 hours post infection. Although there were no detectable differences in the amount of bacteria within an infected cell between the three strains, there was a significant increase in the amount of cellular debris observed in the air spaces of the lungs in the Schu S4 waaY::TrgTn mutant compared to either the Schu S4 or LVS strain. We also studied the interactions of Francisella strains with human AT-II cells in vitro by characterizing the ability of these three strains to invade and replicate within these cells. Gentamicin assay and confocal microscopy both confirmed that F. tularensis Schu S4 replicated robustly within these cells while F. tularensis LVS displayed significantly lower levels of growth over 24 hours, although the strain was able to enter these cells at about the same level as Schu S4 (1 organism per cell, as determined by confocal imaging. The Schu S4 waaY::TrgTn mutant that we have previously described as attenuated for growth in macrophages and mouse virulence displayed interesting properties as well. This mutant induced significant airway inflammation (cell debris and had an attenuated growth phenotype in the human AT-II cells. These

  5. Exacerbation of benzene pneumotoxicity in connexin 32 knockout mice: enhanced proliferation of CYP2E1-immunoreactive alveolar epithelial cells

    International Nuclear Information System (INIS)

    The pulmonary pathogenesis triggered by benzene exposure was studied. Since the role of the connexin 32 (Cx32) gap junction protein in mouse pulmonary pathogenesis has been suggested, in the present study, we explored a possible role of Cx32 in benzene-induced pulmonary pathogenesis using the wild-type (WT) and Cx32 knockout (KO) mice. The mice were exposed to 300 ppm benzene by inhalation for 6 h per day, 5 days per week for a total of 26 weeks, and then sacrificed to evaluate the pneumotoxicity or allowed to live out their life span to evaluate the reversibility of the lesions and tumor incidence. Our results clearly revealed exacerbated pneumotoxicity in the benzene-exposed Cx32 KO mice, characterized by diffuse granulomatous interstitial pneumonia, markedly increased mucin secretion of bronchial/bronchiolar and alveolar epithelial cells, and hyperplastic alveolar epithelial cells positive for CYP2E1. But the results did not indicate any enhancement of pulmonary tumorigenesis in the Cx32 KO mice though the number of animals was small

  6. Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells

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    Peiris Malik

    2010-03-01

    Full Text Available Abstract Avian influenza virus H9N2 isolates cause a mild influenza-like illness in humans. However, the pathogenesis of the H9N2 subtypes in human remains to be investigated. Using a human alveolar epithelial cell line A549 as host, we found that A/Quail/Hong Kong/G1/97 (H9N2/G1, which shares 6 viral "internal genes" with the lethal A/Hong Kong/156/97 (H5N1/97 virus, replicates efficiently whereas other H9N2 viruses, A/Duck/Hong Kong/Y280/97 (H9N2/Y280 and A/Chicken/Hong Kong/G9/97 (H9N2/G9, replicate poorly. Interestingly, we found that there is a difference in the translation of viral protein but not in the infectivity or transcription of viral genes of these H9N2 viruses in the infected cells. This difference may possibly be explained by H9N2/G1 being more efficient on viral protein production in specific cell types. These findings suggest that the H9N2/G1 virus like its counterpart H5N1/97 may be better adapted to the human host and replicates efficiently in human alveolar epithelial cells.

  7. Elastolytic activity and alveolar epithelial type-1 cell damage after chronic LPS inhalation: Effects of dexamethasone and rolipram

    International Nuclear Information System (INIS)

    This study investigated whether a correlation between leukocyte-derived elastolytic activity, alveolar epithelial type-1 cell damage, and leukocyte infiltration of the airways existed in guinea-pigs chronically exposed to inhaled lipopolysaccharide (LPS). The airway pathology of this model, notably the neutrophilia, resembles chronic obstructive pulmonary disease (COPD). The effect of the corticosteroid, dexamethasone, or the phosphodiesterase-4 (PDE4)-inhibitor, rolipram, on these features was studied. Conscious guinea-pigs were exposed for 1 h to single or repeated (nine) doses of LPS (30 μg ml-1). Dexamethasone (20 mg kg-1, ip) or rolipram (1 mg kg-1, ip) was administered 24 and 0.5 h before the first exposure and daily thereafter. Bronchoalveolar lavage fluid (BALF) was removed and elastolytic activity determined as the elastase-like release of Congo Red from impregnated elastin. The presence of the specific epithelial cell type-1 protein (40-42 kDa) RT140 in BALF was identified by Western blotting using a rat monoclonal antibody and semi-quantified by dot-blot analysis. The antibody was found to identify guinea-pig RT140. BALF inflammatory cells, particularly neutrophils and macrophages, and elastolytic activity were increased in chronic LPS-exposed guinea-pigs, the latter by 90%. Chronic LPS exposure also increased (10.5-fold) RT140 levels, indicating significant alveolar epithelial type-1 cell damage. Dexamethasone or rolipram treatment reduced the influx of inflammatory cells, the elastolytic activity (by 40% and 38%, respectively), and RT140 levels (by 50% and 57%, respectively). In conclusion, chronic LPS-exposed guinea-pigs, like COPD, exhibit elastolytic lung damage. This was prevented by a PDE4 inhibitor and supports their development for suppressing this leukocyte-mediated pathology

  8. Activated Alveolar Epithelial Cells Initiate Fibrosis through Secretion of Mesenchymal Proteins

    OpenAIRE

    Yang, Jibing; Wheeler, Sarah E.; Velikoff, Miranda; Kleaveland, Kathryn R.; LaFemina, Michael J.; Frank, James A.; Chapman, Harold A.; Christensen, Paul J; Kim, Kevin K.

    2013-01-01

    Fibrosis is characterized by accumulation of activated fibroblasts and pathological deposition of fibrillar collagens. Activated fibroblasts overexpress matrix proteins and release factors that promote further recruitment of activated fibroblasts, leading to progressive fibrosis. The contribution of epithelial cells to this process remains unknown. Epithelium-directed injury may lead to activation of epithelial cells with phenotypes and functions similar to activated fibroblasts. Prior report...

  9. Perlecan and Dystroglycan act at the basal side of the Drosophila follicular epithelium to maintain epithelial organization

    Science.gov (United States)

    Schneider, Martina; Khalil, Ashraf A.; Poulton, John; Castillejo-Lopez, Casimiro; Egger-Adam, Diane; Wodarz, Andreas; Deng, Wu-Min; Baumgartner, Stefan

    2009-01-01

    Dystroglycan (Dg) is a widely expressed extracellular matrix (ECM) receptor required for muscle viability, synaptogenesis, basement-membrane formation and epithelial development. As an integral component of the Dystrophin-associated glycoprotein complex, Dg plays a central role in linking the ECM and the cytoskeleton. Disruption of this linkage in skeletal muscle leads to various types of muscular dystrophies. In epithelial cells, reduced expression of Dg is associated with increased invasiveness of cancer cells. We have previously shown that Dg is required for epithelial cell polarity in Drosophila, but the mechanisms of this polarizing activity and upstream/downstream components are largely unknown. Using the Drosophila follicle-cell epithelium (FCE) as a model system, we show that the ECM molecule Perlecan (Pcan) is required for maintenance of epithelial-cell polarity. Follicle cells that lack Pcan develop polarity defects similar to those of Dg mutant cells. Furthermore, Dg depends on Pcan but not on Laminin A for its localization in the basal-cell membrane, and the two proteins bind in vitro. Interestingly, the Dg form that interacts with Pcan in the FCE lacks the mucin-like domain, which is thought to be essential for Dg ligand binding activity. Finally, we describe two examples of how Dg promotes the differentiation of the basal membrane domain: (1) by recruiting/anchoring the cytoplasmic protein Dystrophin; and (2) by excluding the transmembrane protein Neurexin. We suggest that the interaction of Pcan and Dg at the basal side of the epithelium promotes basal membrane differentiation and is required for maintenance of cell polarity in the FCE. PMID:16943280

  10. Protein Profiling of Isolated Leukocytes, Myofibroblasts, Epithelial, Basal, and Endothelial Cells from Normal, Hyperplastic, Cancerous, and Inflammatory Human Prostate Tissues

    Directory of Open Access Journals (Sweden)

    Zahraa I. Khamis, Kenneth A. Iczkowski, Ziad J. Sahab, Qing-Xiang Amy Sang

    2010-01-01

    Full Text Available In situ neoplastic prostate cells are not lethal unless they become invasive and metastatic. For cells to become invasive, the prostate gland must undergo degradation of the basement membrane and disruption of the basal cell layer underneath the luminal epithelia. Although the roles of proteinases in breaking down the basement membrane have been well-studied, little is known about the factors that induce basal cell layer disruption, degeneration, and its eventual disappearance in invasive cancer. It is hypothesized that microenvironmental factors may affect the degradation of the basal cell layer, which if protected may prevent tumor progression and invasion. In this study, we have revealed differential protein expression patterns between epithelial and stromal cells isolated from different prostate pathologies and identified several important epithelial and stromal proteins that may contribute to inflammation and malignant transformation of human benign prostate tissues to cancerous tissues using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and proteomics methods. Cellular retinoic acid-binding protein 2 was downregulated in basal cells of benign prsotate. Caspase-1 and interleukin-18 receptor 1 were highly expressed in leukocytes of prostate cancer. Proto-oncogene Wnt-3 was downregulated in endothelial cells of prostatitis tissue and tyrosine phosphatase non receptor type 1 was only found in normal and benign endothelial cells. Poly ADP-ribose polymerase 14 was downregulated in myofibroblasts of prostatitis tissue. Interestingly, integrin alpha-6 was upregulated in epithelial cells but not detected in myofibroblasts of prostate cancer. Further validation of these proteins may generate new strategies for the prevention of basal cell layer disruption and subsequent cancer invasion.

  11. 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

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    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.

  12. Cytotoxicity and inflammation in human alveolar epithelial cells following exposure to occupational levels of gold and silver nanoparticles

    International Nuclear Information System (INIS)

    While inhalation represents one of the most likely routes of exposure, the toxicity and response of nanoparticles at concentrations expected from such an exposure are not well understood. Here we characterized the in vitro response of human A549 adenocarcinomic alveolar epithelial cells following exposure to gold (AuNP) and silver (AgNP) nanoparticles at levels approximating an occupational exposure. Changes in neither oxidative stress nor cytotoxicity were significantly affected by exposure to AgNPs and AuNPs, regardless of NP type (Ag vs. Au), concentration, surface ligand (citrate or tannic acid), or size. An inflammatory response was, however, observed in response to 20 nm AgNPs and 20 nm AuNPs, where significant differences in the release of interleukin (IL)-8 but not IL-6 were observed. Additional data demonstrated that increased IL-8 secretion was strongly dependent on both nanoparticle size and concentration. Overall these data suggest that, while not acutely toxic, occupational exposure to AuNPs and AgNPs may trigger a significant inflammatory response in alveolar epithelium. Moreover, the differential responses in IL-8 and IL-6 secretion suggest that NPs may induce a response pathway that is distinct from those commonly elicited by allergens and pathogens.

  13. Intratracheal Administration of Recombinant Human Keratinocyte Growth Factor Promotes Alveolar Epithelial Cell Proliferation during Compensatory Lung Growth in Rat

    International Nuclear Information System (INIS)

    Keratinocyte growth factor (KGF) is considered to be one of the most important mitogens for lung epithelial cells. The objectives of this study were to confirm the effectiveness of intratracheal injection of recombinant human KGF (rhKGF) during compensatory lung growth and to optimize the instillation protocol. Here, trilobectomy in adult rat was performed, followed by intratracheal rhKGF instillation with low (0.4 mg/kg) and high (4 mg/kg) doses at various time-points. The proliferation of alveolar cells was assessed by the immunostaining for proliferating cell nuclear antigen (PCNA) in the residual lung. We also investigated other immunohistochemical parameters such as KGF, KGF receptor and surfactant protein A as well as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Consequently, intratracheal single injection of rhKGF in high dose group significantly increased PCNA labeling index (LI) of alveolar cells in the remaining lung. Surprisingly, there was no difference in PCNA LI between low and high doses of rhKGF with daily injection, and PCNA LI reached a plateau level with 2 days-consecutive administration (about 60%). Our results indicate that even at low dose, daily intratracheal injection is effective to maintain high proliferative states during the early phase of compensatory lung growth

  14. Detection of alveolar epithelial injury by Tc-99m DTPA radioaerosol inhalation lung scan in rheumatoid arthritis patients

    International Nuclear Information System (INIS)

    Rheumatoid arthritis (RA) is a systemic autoimmune disorder primarily involving the joints. Lung alterations in RA may be primary or secondary to pharmacological treatments and may involve the alveoli, interstitium, airways and/or pleura. Technetium-99 m diethylenetriaminepentaacetic acid (Tc-99m DTPA) aerosol inhalation scintigraphy is a sensitive and noninvasive test commonly employed to assess pulmonary epithelial membrane permeability. The purpose of this study was to investigate the changes of pulmonary alveolar epithelial permeability in patients with RA, to determine the relationship between the clearance rate of Tc-99m DTPA and pulmonary function test (PFT) results, and to determine the relationship between the clearance rate of Tc-99m DTPA and clinical parameters of disease. Twenty-five patients with RA but without lung alterations were included in the study. The patients were 22 females, and 3 males; mean age 53.6±8.7 years. Technetium-99m DTPA aerosol inhalation scintigraphy was performed on the study and healthy control groups. Clearance half times (T1/2) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. There were no significant differences in the mean T1/2 or mean PI values between the RA patients and control subjects. No correlation was found between the mean T1/2 values of Tc-99m DTPA clearance and activity of RA, clinical values, or the spirometric measurements except FEV1/FVC and functional status in RA patients (p=0.02, p=0.01, respectively). However, a weak correlation was found between duration of disease and T1/2 values of Tc-99m DTPA clearance (p=0.006). PI values tended to correlate with FEF25-75, although, this was not statistically significant (p=0.057). This study shows that no changes occur in alveolar-capillary permeability in RA patients without lung alterations. (author)

  15. Isolation of alveolar epithelial type II progenitor cells from adult human lungs

    OpenAIRE

    Fujino, Naoya; Kubo, Hiroshi; Suzuki, Takaya; Ota, Chiharu; Hegab, Ahmed E.; He, Mei; Suzuki, Satoshi; Suzuki, Takashi; Yamada, Mitsuhiro; Kondo, Takashi; Kato, Hidemasa; Yamaya, Mutsuo

    2010-01-01

    Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However, a progenitor population for alveolar type II (ATII) cells in adult human lungs has not been identified. The aim of this study is to isolate progenitor cells from adult human lungs with the ability to differentiate into ATII cells. We isolated colony-forming cells that had the capability for self-renewal and the potential to generate ATII cells in vitro. These undifferentiated progenitor cells ...

  16. Enolase 1 (ENO1 and protein disulfide-isomerase associated 3 (PDIA3 regulate Wnt/β-catenin-driven trans-differentiation of murine alveolar epithelial cells

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    Kathrin Mutze

    2015-08-01

    Full Text Available The alveolar epithelium represents a major site of tissue destruction during lung injury. It consists of alveolar epithelial type I (ATI and type II (ATII cells. ATII cells are capable of self-renewal and exert progenitor function for ATI cells upon alveolar epithelial injury. Cell differentiation pathways enabling this plasticity and allowing for proper repair, however, are poorly understood. Here, we applied proteomics, expression analysis and functional studies in primary murine ATII cells to identify proteins and molecular mechanisms involved in alveolar epithelial plasticity. Mass spectrometry of cultured ATII cells revealed a reduction of carbonyl reductase 2 (CBR2 and an increase in enolase 1 (ENO1 and protein disulfide-isomerase associated 3 (PDIA3 protein expression during ATII-to-ATI cell trans-differentiation. This was accompanied by increased Wnt/β-catenin signaling, as analyzed by qRT-PCR and immunoblotting. Notably, ENO1 and PDIA3, along with T1α (podoplanin; an ATI cell marker, exhibited decreased protein expression upon pharmacological and molecular Wnt/β-catenin inhibition in cultured ATII cells, whereas CBR2 levels were stabilized. Moreover, we analyzed primary ATII cells from mice with bleomycin-induced lung injury, a model exhibiting activated Wnt/β-catenin signaling in vivo. We observed reduced CBR2 significantly correlating with surfactant protein C (SFTPC, whereas ENO1 and PDIA3 along with T1α were increased in injured ATII cells. Finally, siRNA-mediated knockdown of ENO1, as well as PDIA3, in primary ATII cells led to reduced T1α expression, indicating diminished cell trans-differentiation. Our data thus identified proteins involved in ATII-to-ATI cell trans-differentiation and suggest a Wnt/β-catenin-driven functional role of ENO1 and PDIA3 in alveolar epithelial cell plasticity in lung injury and repair.

  17. IL-8 inhibits cAMP-stimulated alveolar epithelial fluid transport via a GRK2/PI3K-dependent mechanism

    Science.gov (United States)

    Roux, Jérémie; McNicholas, Carmel M.; Carles, Michel; Goolaerts, Arnaud; Houseman, Benjamin T.; Dickinson, Dale A.; Iles, Karen E.; Ware, Lorraine B.; Matthay, Michael A.; Pittet, Jean-François

    2013-01-01

    Patients with acute lung injury (ALI) who retain maximal alveolar fluid clearance (AFC) have better clinical outcomes. Experimental and small clinical studies have shown that β2-adrenergic receptor (β2AR) agonists enhance AFC via a cAMP-dependent mechanism. However, two multicenter phase 3 clinical trials failed to show that β2AR agonists provide a survival advantage in patients with ALI. We hypothesized that IL-8, an important mediator of ALI, directly antagonizes the alveolar epithelial response to β2AR agonists. Short-circuit current and whole-cell patch-clamping experiments revealed that IL-8 or its rat analog CINC-1 decreases by 50% β2AR agonist-stimulated vectorial Cl− and net fluid transport across rat and human alveolar epithelial type II cells via a reduction in the cystic fibrosis transmembrane conductance regulator activity and biosynthesis. This reduction was mediated by heterologous β2AR desensitization and down-regulation (50%) via the G-protein-coupled receptor kinase 2 (GRK2)/PI3K signaling pathway. Inhibition of CINC-1 restored β2AR agonist-stimulated AFC in an experimental model of ALI in rats. Finally, consistent with the experimental results, high pulmonary edema fluid levels of IL-8 (>4000 pg/ml) were associated with impaired AFC in patients with ALI. These results demonstrate a novel role for IL-8 in inhibiting β2AR agonist-stimulated alveolar epithelial fluid transport via GRK2/PI3K-dependent mechanisms.—Roux, J., McNicholas, C. M., Carles, M., Goolaerts, A., Houseman, B. T., Dickinson, D. A., Iles, K. E., Ware, L. B., Matthay, M. A., Pittet, J.-F. IL-8 inhibits cAMP-stimulated alveolar epithelial fluid transport via a GRK2/PI3K-dependent mechanism. PMID:23221335

  18. Cadmium exposure down-regulates 8-oxoguanine DNA glycosylase expression in rat lung and alveolar epithelial cells

    International Nuclear Information System (INIS)

    The current study tested the hypothesis that the pulmonary carcinogenic potential of cadmium (Cd) is related to its ability to inhibit the expression (mRNA and protein) and activity of 8-oxoguanine-DNA glycosylase (OGG1), a base excision repair (BER) enzyme that functions to preferentially excise pre-mutagenic 7,8-dihydro-8-oxoguanine (8-oxoG) from DNA. We demonstrate that a single Cd aerosol exposure of adult male Lewis rats causes time- and dose-dependent down-regulation in the pulmonary levels of rOGG1 mRNA and OGG1 protein, quantified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays and western analyses, respectively. Immunohistochemical studies confirmed that Cd inhalation reduces the relative amount of OGG1 in lungs of exposed animals without altering its over-all distribution within the lung, which appears to be more prominent within the alveolar epithelium. In agreement with our in vivo studies, we show that OGG1 expression is also attenuated in alveolar epithelial cell cultures exposed to CdCl2 either acutely or by repeated passaging in Cd-containing medium. The effects caused by Cd were observed in cells that show no loss in viability, as assessed by colony forming ability, the MTT assay, and propidium iodide membrane permeability studies. Nuclear extracts prepared from Cd-treated cells also exhibit a reduction in the ability to nick a synthetic oligonucleotide containing 8-oxoG. We conclude from these studies that Cd causes suppression of OGG1 in the lung and that this mechanism may, in part, play a role in the Cd carcinogenic process

  19. Activated alveolar epithelial cells initiate fibrosis through autocrine and paracrine secretion of connective tissue growth factor

    OpenAIRE

    Yang, Jibing; Velikoff, Miranda; Canalis, Ernesto; Horowitz, Jeffrey C.; Kim, Kevin K.

    2014-01-01

    Fibrogenesis involves a pathological accumulation of activated fibroblasts and extensive matrix remodeling. Profibrotic cytokines, such as TGF-β, stimulate fibroblasts to overexpress fibrotic matrix proteins and induce further expression of profibrotic cytokines, resulting in progressive fibrosis. Connective tissue growth factor (CTGF) is a profibrotic cytokine that is indicative of fibroblast activation. Epithelial cells are abundant in the normal lung, but their contribution to fibrogenesis...

  20. CCR2 and CXCR3 agonistic chemokines are differently expressed and regulated in human alveolar epithelial cells type II

    Directory of Open Access Journals (Sweden)

    Prasse Antje

    2005-07-01

    Full Text Available Abstract The attraction of leukocytes from circulation to inflamed lungs depends on the activation of both the leukocytes and the resident cells within the lung. In this study we determined gene expression and secretion patterns for monocyte chemoattractant protein-1 (MCP-1/CCL2 and T-cell specific CXCR3 agonistic chemokines (Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11 in TNF-α-, IFN-γ-, and IL-1β-stimulated human alveolar epithelial cells type II (AEC-II. AEC-II constitutively expressed high level of CCL2 mRNA in vitro and in situ , and released CCL2 protein in vitro . Treatment of AEC-II with proinflammatory cytokines up-regulated both CCL2 mRNA expression and release of immunoreactive CCL2, whereas IFN-γ had no effect on CCL2 release. In contrast, CXCR3 agonistic chemokines were not detected in freshly isolated AEC-II or in non-stimulated epithelial like cell line A549. IFN-γ, alone or in combination with IL-1β and TNF-α resulted in an increase in CXCL10, CXCL11, and CXCL9 mRNA expression and generation of CXCL10 protein by AEC-II or A549 cells. CXCL10 gene expression and secretion were induced in dose-dependent manner after cytokine-stimulation of AEC-II with an order of potency IFN-γ>>IL-1β ≥ TNF-α. Additionally, we localized the CCL2 and CXCL10 mRNAs in human lung tissue explants by in situ hybridization, and demonstrated the selective effects of cytokines and dexamethasone on CCL2 and CXCL10 expression. These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung, with the ability to respond to locally generated cytokines and to produce potent mediators of the local inflammatory response.

  1. A Novel Approach for Ovine Primary Alveolar Epithelial Type II Cell Isolation and Culture from Fresh and Cryopreserved Tissue Obtained from Premature and Juvenile Animals

    OpenAIRE

    Marcinkiewicz, Mariola M.; Baker, Sandy T.; Jichuan Wu; Terrence L Hubert; Wolfson, Marla R.

    2016-01-01

    The in vivo ovine model provides a clinically relevant platform to study cardiopulmonary mechanisms and treatments of disease; however, a robust ovine primary alveolar epithelial type II (ATII) cell culture model is lacking. The objective of this study was to develop and optimize ovine lung tissue cryopreservation and primary ATII cell culture methodologies for the purposes of dissecting mechanisms at the cellular level to elucidate responses observed in vivo. To address this, we established ...

  2. Increased ectodomain shedding of cell adhesion molecule 1 as a cause of type II alveolar epithelial cell apoptosis in patients with idiopathic interstitial pneumonia

    OpenAIRE

    Yoneshige, Azusa; Hagiyama, Man; Inoue, Takao; Mimae, Takahiro; Kato, Takashi; Okada, Morihito; Enoki, Eisuke; Ito, Akihiko

    2015-01-01

    Background Lung alveolar epithelial cell (AEC) apoptosis has attracted attention as an early pathogenic event in the development of idiopathic interstitial pneumonia (IIP); however, the causative mechanism remains unclear. Cell adhesion molecule 1 (CADM1) is an AEC adhesion molecule in the immunoglobulin superfamily. It generates a membrane-associated C-terminal fragment, αCTF, through protease-mediated ectodomain shedding, termed α-shedding. Increased CADM1 α-shedding contributes to AEC apop...

  3. Environmental particulate (PM2.5 augments stiffness-induced alveolar epithelial cell mechanoactivation of transforming growth factor beta.

    Directory of Open Access Journals (Sweden)

    Marilyn M Dysart

    Full Text Available Dysfunctional pulmonary homeostasis and repair, including diseases such as pulmonary fibrosis (PF, chronic obstructive pulmonary disease (COPD, and tumorigenesis have been increasing over the past decade, a fact that heavily implicates environmental influences. Several investigations have suggested that in response to increased transforming growth factor--beta (TGFβ signaling, the alveolar type II (ATII epithelial cell undergoes phenotypic changes that may contribute to the complex pathobiology of PF. We have previously demonstrated that increased tissue stiffness associated with PF is a potent extracellular matrix (ECM signal for epithelial cell activation of TGFβ. The work reported here explores the relationship between tissue stiffness and exposure to environmental stimuli in the activation of TGFβ. We hypothesized that exposure of ATII cells to fine particulate matter (PM2.5 will result in enhanced cell contractility, TGFβ activation, and subsequent changes to ATII cell phenotype. ATII cells were cultured on increasingly stiff substrates with or without addition of PM2.5. Exposure to PM2.5 resulted in increased activation of TGFβ, increased cell contractility, and elongation of ATII cells. Most notably, on 8 kPa substrates, a stiffness greater than normal but less than established fibrotic lung, addition of PM2.5 resulted in increased cortical cell stiffness, enhanced actin staining and cell elongation; a result not seen in the absence of PM2.5. Our work suggests that PM2.5 exposure additionally enhances the existing interaction between ECM stiffness and TGFβ that has been previously reported. Furthermore, we show that this additional enhancement is likely a consequence of intracellular reactive oxygen species (ROS leading to increased TGFβ signaling events. These results highlight the importance of both the micromechanical and biochemical environment in lung disease initiation and suggest that individuals in early stages of lung

  4. Genomic signature and toxicogenomics comparison of polycationic gene delivery nanosystems in human alveolar epithelial A549 cells

    Directory of Open Access Journals (Sweden)

    J Barar

    2009-10-01

    Full Text Available "nBackground and the purpose of the study: Of the gene delivery systems, non-viral polycationic gene delivery nanosystems have been alternatively exploited as a relatively safe delivery reagents compared to viral vectors. However, little is known about the genomic impacts of these delivery systems in target cells/tissues. In this study, the toxicogenomics and genotoxicity potential of some selected polycationic lipid/polymer based nanostructures (i.e., Oligofectamine® (OF, starburst polyamidoamine Polyfect® (PF and diaminobutane (DAB dendrimers were investigated in human alveolar epithelial A549 cells. "nMethods: To study the nature and the ontology of the gene expression changes in A549 cells upon treatment with polycationic nanostructures, MTT assay and microarray gene expression profiling methodology were employed. For microarray analysis, cyanine (Cy3/Cy5 labeled cDNA samples from treated and untreated cells were hybridized on target arrays housing 200 genes. "nResults and major conclusions: The polycationic nanosystems induced significant gene expression changes belonging to different genomic ontologies such as cell defence and apoptosis pathways. These data suggest that polycationic nanosystems can elicit multiple gene expression changes in A549 cells upon their chemical structures and interactions with cellular/subcellular components. Such impacts may interfere with the main goals of the desired genemedicine.

  5. Assessment of alveolar epithelial permeability in Behcet's disease with 99mTc-DTPA aerosol scintigraphy

    International Nuclear Information System (INIS)

    Behcet's disease (BD) is a multisystem disorder characterized by vasculitis, and consists of a triad of recurrent ulcers of the oral and genital mucosa with relapsing uveitis. The prevalance of pulmonary involvement varies in the range of 1-10% in various studies and its complications are severe and life threatening. In this study, we investigated the changes of pulmonary epithelial permeability of patients with BD using technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) aerosol scintigraphy, so as to begin the therapy regimen as soon as possible. Twenty-one nonsmoking patients with BD (8 women, 13 men; mean age 38.67±8.86 years) and 15 healthy volunteer nonsmoking controls (8 women, 7 men; mean age 50.87±12.45 years) underwent 99mTc-DTPA aerosol inhalation scintigraphy and pulmonary function tests (PFTs). Subjects inhaled 1480 MBq of 99mTc-DTPA for 4 min in the supine position. Scintigraphic data were recorded dynamically (1 frame/min) in the posterior projection on a 64 x 64 matrix for a 30-min period using a double-headed gamma camera (Infinia, GE, Tirat Hacarmel, Israel) equipped with a low-energy all-purpose parallel hole collimator. Half time of 99mTc-DTPA clearance (T1/2) was calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was also calculated by dividing the peripheral total counts by the sum of the peripheral and central total counts on the first minute image, in order to quantify the distribution of the inhaled aerosol. The clearance half time of 99mTc-DTPA radioaerosols in the BD patients (24.81±6.22 min) was faster than in the normal control group (46.53±22.41 min) (P=0.004). There was also a significant difference between PI of the patients with BD (0.15±0.03) and that of the controls (0.21±0.06) (P=0.002). No correlation was found between the mean T1/2 values of 99mTc-DTPA clearance or the spirometric measurements in the BD patients. Penetration indices were not correlated with PET in the BD

  6. Basal but not luminal mammary epithelial cells require PI3K/mTOR signaling for Ras-driven overgrowth.

    Science.gov (United States)

    Plichta, Kristin A; Mathers, Jessica L; Gestl, Shelley A; Glick, Adam B; Gunther, Edward J

    2012-11-15

    The mammary ducts of humans and mice are comprised of two main mammary epithelial cell (MEC) subtypes: a surrounding layer of basal MECs and an inner layer of luminal MECs. Breast cancer subtypes show divergent clinical behavior that may reflect properties inherent in their MEC compartment of origin. How the response to a cancer-initiating genetic event is shaped by MEC subtype remains largely unexplored. Using the mouse mammary gland, we designed organotypic three-dimensional culture models that permit challenge of discrete MEC compartments with the same oncogenic insult. Mammary organoids were prepared from mice engineered for compartment-restricted coexpression of oncogenic H-RAS(G12V) together with a nuclear fluorescent reporter. Monitoring of H-RAS(G12V)-expressing MECs during extended live cell imaging permitted visualization of Ras-driven phenotypes via video microscopy. Challenging either basal or luminal MECs with H-RAS(G12V) drove MEC proliferation and survival, culminating in aberrant organoid overgrowth. In each compartment, Ras activation triggered modes of collective MEC migration and invasion that contrasted with physiologic modes used during growth factor-initiated branching morphogenesis. Although basal and luminal Ras activation produced similar overgrowth phenotypes, inhibitor studies revealed divergent use of Ras effector pathways. Blocking either the phosphoinositide 3-kinase or the mammalian target of rapamycin pathway completely suppressed Ras-driven invasion and overgrowth of basal MECs, but only modestly attenuated Ras-driven phenotypes in luminal MECs. We show that MEC subtype defines signaling pathway dependencies downstream of Ras. Thus, cells-of-origin may critically determine the drug sensitivity profiles of mammary neoplasia. PMID:23010075

  7. Direct and indirect air particle cytotoxicity in human alveolar epithelial cells.

    Science.gov (United States)

    Orona, N S; Astort, F; Maglione, G A; Saldiva, P H N; Yakisich, J S; Tasat, D R

    2014-08-01

    Air particulate matter has been associated with adverse impact on the respiratory system leading to cytotoxic and proinflammatory effects. The biological mechanisms behind these associations may be initiated by inhaled small size particles, particle components (soluble fraction) and/or mediators released by particle-exposed cells (conditioned media). The effect of Urban Air Particles from Buenos Aires (UAP-BA) and Residual Oil Fly Ash (ROFA) a surrogate of ambient air pollution, their Soluble Fractions (SF) and Conditioned Media (CM) on A549 lung epithelial cells was examined. After 24 h exposure to TP (10 and 100 μg/ml), SF or CM, several biological parameters were assayed on cultured A549 cells. We tested cell viability by MTT, superoxide anion (O₂(-)) generation by NBT and proinflammatory cytokine (TNFα, IL-6 and IL-8) production by ELISA. UAP-BA particles or its SF (direct effect) did not modify cell viability and generation of O₂(-) for any of the doses tested. On the contrary, UAP-BA CM (indirect effect) reduced cell viability and increased both generation of O₂(-) and IL-8 production. Exposure to ROFA particles, SF or ROFA CM reduced proliferation and O₂(-) but, stimulated IL-8. It is worth to note that UAP-BA and ROFA depicted distinct effects on particle-exposed A549 cells implicating morphochemical dependence. These in vitro findings support the hypothesis that particle-induced lung inflammation and disease may involve lung-derived mediators. PMID:24590061

  8. Overexpression of sICAM-1 in the Alveolar Epithelial Space Results in an Exaggerated Inflammatory Response and Early Death in Gram Negative Pneumonia

    Directory of Open Access Journals (Sweden)

    Curtis Jeffery L

    2011-01-01

    Full Text Available Abstract Background A sizeable body of data demonstrates that membrane ICAM-1 (mICAM-1 plays a significant role in host defense in a site-specific fashion. On the pulmonary vascular endothelium, mICAM-1 is necessary for normal leukocyte recruitment during acute inflammation. On alveolar epithelial cells (AECs, we have shown previously that the presence of normal mICAM-1 is essential for optimal alveolar macrophage (AM function. We have also shown that ICAM-1 is present in the alveolar space as a soluble protein that is likely produced through cleavage of mICAM-1. Soluble intercellular adhesion molecule-1 (sICAM-1 is abundantly present in the alveolar lining fluid of the normal lung and could be generated by proteolytic cleavage of mICAM-1, which is highly expressed on type I AECs. Although a growing body of data suggesting that intravascular sICAM-1 has functional effects, little is known about sICAM-1 in the alveolus. We hypothesized that sICAM-1 in the alveolar space modulates the innate immune response and alters the response to pulmonary infection. Methods Using the surfactant protein C (SPC promoter, we developed a transgenic mouse (SPC-sICAM-1 that constitutively overexpresses sICAM-1 in the distal lung, and compared the responses of wild-type and SPC-sICAM-1 mice following intranasal inoculation with K. pneumoniae. Results SPC-sICAM-1 mice demonstrated increased mortality and increased systemic dissemination of organisms compared with wild-type mice. We also found that inflammatory responses were significantly increased in SPC-sICAM-1 mice compared with wild-type mice but there were no difference in lung CFU between groups. Conclusions We conclude that alveolar sICAM-1 modulates pulmonary inflammation. Manipulating ICAM-1 interactions therapeutically may modulate the host response to Gram negative pulmonary infections.

  9. Microarray identifies ADAM family members as key responders to TGF-β1 in alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Walls Dermot

    2006-09-01

    Full Text Available Abstract The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF remain elusive. Transforming Growth Factor beta 1(TGF-β1 is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549 in response to TGF-β1, IL-4 and IL-13 and Epstein Barr virus. A549 cells were exposed to 10 ng/ml TGF-β1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO databases for baited cluster analysis of ECM associated genes. Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-β1, suggesting a potential role for these molecules in ECM accumulation in IPF.

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

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    Dagbjort H Petursdottir

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

  11. cDNA microarray analysis of rat alveolar epithelial cells following exposure to organic extract of diesel exhaust particles

    International Nuclear Information System (INIS)

    Diesel exhaust particles (DEP) induce pulmonary diseases including asthma and chronic bronchitis. Comprehensive evaluation is required to know the mechanisms underlying the effects of air pollutants including DEP on lung diseases. Using a cDNA microarray, we examined changes in gene expression in SV40T2 cells, a rat alveolar type II epithelial cell line, following exposure to an organic extract of DEP. We identified candidate sensitive genes that were up- or down-regulated in response to DEP. The cDNA microarray analysis revealed that a 6-h exposure to the DEP extract (30 μg/ml) increased (>2-fold) the expression of 51 genes associated with drug metabolism, antioxidation, cell cycle/proliferation/apoptosis, coagulation/fibrinolysis, and expressed sequence tags (ESTs), and decreased (<0.5-fold) that of 20 genes. In the present study, heme oxygenase (HO)-1, an antioxidative enzyme, showed the maximum increase in gene expression; and type II transglutaminase (TGM-2), a regulator of coagulation, showed the most prominent decrease among the genes. We confirmed the change in the HO-1 protein level by Western blot analysis and that in the enzyme activity of TGM-2. The organic extract of DEP increased the expression of HO-1 protein and decreased the enzyme activity of TGM-2. Furthermore, these effects of DEP on either HO-1 or TGM-2 were reduced by N-acetyl-L-cysteine (NAC), thus suggesting that oxidative stress caused by this organic fraction of DEP may have induced these cellular responses. Therefore, an increase in HO-1 and a decrease in TGM-2 might be good markers of the biological response to organic compounds of airborne particulate substances

  12. Expression of polycomb protein BMI-1 maintains the plasticity of basal bronchial epithelial cells.

    Science.gov (United States)

    Torr, Elizabeth; Heath, Meg; Mee, Maureen; Shaw, Dominick; Sharp, Tyson V; Sayers, Ian

    2016-08-01

    The airway epithelium is altered in respiratory disease and is thought to contribute to disease etiology. A caveat to disease research is that the technique of isolation of bronchial epithelial cells from patients is invasive and cells have a limited lifespan. The aim of this study was to extensively characterize the plasticity of primary human bronchial epithelial cells that have been engineered to delay cell senescence including the ability of these cells to differentiate. Cells were engineered to express BMI-1 or hTERT using viral vector systems. Cells were characterized at passage (p) early (p5), mid (p10), and late (p15) stage for: BMI-1, p16, and CK14 protein expression, viability and the ability to differentiate at air-liquid interface (ALI), using a range of techniques including immunohistochemistry (IHC), immunofluorescence (IF), transepithelial electrical resistance (TEER), scanning electron microscopy (SEM), MUC5AC and beta tubulin (BTUB) staining. BMI-1-expressing cells maintained elevated levels of the BMI-1 protein and the epithelial marker CK14 and showed a suppression of p16. BMI-1-expressing cells had a viability advantage, differentiated at ALI, and had a normal karyotype. In contrast, hTERT-expressing cells had a reduced viability, showed limited differentiation, and had an abnormal karyotype. We therefore provide extensive characterization of the plasticity of BMI-1 expressing cells in the context of the ALI model. These cells retain properties of wild-type cells and may be useful to characterize respiratory disease mechanisms in vitro over sustained periods. PMID:27558999

  13. Assessment of alveolar epithelial permeability in progressive systemic sclerosis (PSS) using 99mTc-DTPA (diethylene triamine penta acetate) aerosol inhalation

    International Nuclear Information System (INIS)

    To evaluate alveolar epithelial damage in PSS, we studied pulmonary epithelial permeability by measuring the clearance of inhaled 99mTc-DTPA aerosol and performing thin slice CT scan, pulmonary function tests and right heart catheterization in 28 patients with PSS. The 99mTc-DTPA clearance rate (kep value) in PSS was greater than in 11 non-smoking normal subjects (18.2±7.63x10-3/min vs. 9.12±0.77x10-3/min, p2. In contrast, the kep value showed significant correlations with %DLco (diffusing capacity for carbon monoxide), extent of interstitial lesions evaluated by CT scan (CT score), and mean pulmonary artery pressure. On the other hand, the kep value was high in some patients with normal CT scan and normal %DLco. These findings indicate that pulmonary interstitial lesions in PSS are accompanied by alveolar epithelial damage, and that the clearance of 99mTc-DTPA may be an early predictor of interstitial change. (author)

  14. Pneumocystis carinii major surface glycoprotein induces interleukin-8 and monocyte chemoattractant protein-1 release from a human alveolar epithelial cell line

    DEFF Research Database (Denmark)

    Benfield, T L; Lundgren, Bettina; Shelhamer, J H;

    1999-01-01

    BACKGROUND: The major surface glycoprotein (MSG) is an abundant, immunogenic glycoprotein located on the surface of Pneumocystis carinii. Little is known about the proinflammatory effects of MSG. DESIGN: We have investigated the effect of human MSG on the secretion of the chemokines interleukin 8...... in response to MSG stimulation occurred by 4 h and persisted throughout 8 h of stimulation. CONCLUSION: These findings suggest that MSG can alter alveolar epithelial cytokine release and may be capable of modulating the local inflammatory response in this manner....

  15. Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone

    Directory of Open Access Journals (Sweden)

    Koide Michio

    2008-05-01

    Full Text Available Abstract Background Legionella pneumophila pneumonia often exacerbates acute lung injury (ALI and acute respiratory distress syndrome (ARDS. Apoptosis of alveolar epithelial cells is considered to play an important role in the pathogenesis of ALI and ARDS. In this study, we investigated the precise mechanism by which A549 alveolar epithelial cells induced by L. pneumophila undergo apoptosis. We also studied the effect of methyl prednisolone on apoptosis in these cells. Methods Nuclear deoxyribonucleic acid (DNA fragmentation and caspase activation in L. pneumophila-infected A549 alveolar epithelial cells were assessed using the terminal deoxyribonucleotidyl transferase-mediated triphosphate (dUTP-biotin nick end labeling method (TUNEL method and colorimetric caspase activity assays. The virulent L. pneumophila strain AA100jm and the avirulent dotO mutant were used and compared in this study. In addition, we investigated whether methyl prednisolone has any influence on nuclear DNA fragmentation and caspase activation in A549 alveolar epithelial cells infected with L. pneumophila. Results The virulent strain of L. pneumophila grew within A549 alveolar epithelial cells and induced subsequent cell death in a dose-dependent manner. The avirulent strain dotO mutant showed no such effect. The virulent strains of L. pneumophila induced DNA fragmentation (shown by TUNEL staining and activation of caspases 3, 8, 9, and 1 in A549 cells, while the avirulent strain did not. High-mobility group box 1 (HMGB1 protein was released from A549 cells infected with virulent Legionella. Methyl prednisolone (53.4 μM did not influence the intracellular growth of L. pneumophila within alveolar epithelial cells, but affected DNA fragmentation and caspase activation of infected A549 cells. Conclusion Infection of A549 alveolar epithelial cells with L. pneumophila caused programmed cell death, activation of various caspases, and release of HMGB1. The dot/icm system, a

  16. Alteration in Intrapulmonary Pharmacokinetics of Aerosolized Model Compounds Due to Disruption of the Alveolar Epithelial Barriers Following Bleomycin-Induced Pulmonary Fibrosis in Rats.

    Science.gov (United States)

    Togami, Kohei; Chono, Sumio; Tada, Hitoshi

    2016-03-01

    Idiopathic pulmonary fibrosis is a lethal lung disease that is characterized by the accumulation of extracellular matrix and a change in lung structure. In this study, intrapulmonary pharmacokinetics of aerosolized model compounds were evaluated using rats with bleomycin-induced pulmonary fibrosis. Aerosol formulations of indocyanine green, 6-carboxyfluorescein (6-CF), and fluorescein isothiocyanate dextrans (FD; 4.4, 10, 70, and 250 kDa) were administered to rat lungs using a MicroSprayer. Indocyanine green fluorescence signals were significantly weaker in fibrotic lungs than in control lungs and 6-CF and FD concentrations in the plasma of pulmonary fibrotic animals were markedly higher than in the plasma of control animals. Moreover, disrupted epithelial tight junctions, including claudins-1, -3, and -5, were observed in pulmonary fibrotic lesions using immunofluorescence microscopy. In addition, destruction of tight junctions on model alveolar epithelial cells (NCI-H441) by transforming growth factor-β1 treatment enhanced the permeability of 6-CF and FDs through NCI-H441 cell monolayers. These results indicate that aerosolized drugs are easily distributed into the plasma after leakage through damaged tight junctions of alveolar epithelium. Therefore, the development of delivery systems for anti-fibrotic agents to improve intrapulmonary pharmacokinetics may be necessary for effective idiopathic pulmonary fibrosis therapy. PMID:26886341

  17. Permanent alveolar collapse is the predominant mechanism in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Todd, Nevins W; Atamas, Sergei P; Luzina, Irina G; Galvin, Jeffrey R

    2015-08-01

    Alveolar epithelial cell loss and impaired epithelial cell regeneration are currently accepted as central initiating events in idiopathic pulmonary fibrosis (IPF), but subsequent downstream effects remain uncertain. The most accepted downstream effect is aberrant and dysregulated mesenchymal cell proliferation and excess extracellular matrix (ECM) accumulation. However, biochemical and imaging studies have perhaps somewhat surprisingly indicated little increase in total lung collagen and lung tissue, and have rather shown a substantial decrease in lung aeration and lung air volume. Loss of tissue aeration is a consequence of alveolar collapse, which occurs in IPF as a result of apposition and septal incorporation of denuded basal lamina. Permanent alveolar collapse is well-documented following epithelial injury, has the ability to mimic interstitial fibrosis radiologically and histologically, and is a better supported explanation than dysregulated fibroblast proliferation and excess ECM accumulation for the constellation of findings in patients with IPF. PMID:26165208

  18. Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment.

    Science.gov (United States)

    Saito, Atsushi; Nikolaidis, Nikolaos M; Amlal, Hassane; Uehara, Yasuaki; Gardner, Jason C; LaSance, Kathleen; Pitstick, Lori B; Bridges, James P; Wikenheiser-Brokamp, Kathryn A; McGraw, Dennis W; Woods, Jason C; Sabbagh, Yves; Schiavi, Susan C; Altinişik, Göksel; Jakopović, Marko; Inoue, Yoshikazu; McCormack, Francis X

    2015-11-11

    Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive lung disorder associated with progressive accumulation of calcium phosphate microliths. Inactivating mutations in SLC34A2, which encodes the NPT2b sodium-dependent phosphate cotransporter, has been proposed as a cause of PAM. We show that epithelial deletion of Npt2b in mice results in a progressive pulmonary process characterized by diffuse alveolar microlith accumulation, radiographic opacification, restrictive physiology, inflammation, fibrosis, and an unexpected alveolar phospholipidosis. Cytokine and surfactant protein elevations in the alveolar lavage and serum of PAM mice and confirmed in serum from PAM patients identify serum MCP-1 (monocyte chemotactic protein 1) and SP-D (surfactant protein D) as potential biomarkers. Microliths introduced by adoptive transfer into the lungs of wild-type mice produce marked macrophage-rich inflammation and elevation of serum MCP-1 that peaks at 1 week and resolves at 1 month, concomitant with clearance of stones. Microliths isolated by bronchoalveolar lavage readily dissolve in EDTA, and therapeutic whole-lung EDTA lavage reduces the burden of stones in the lungs. A low-phosphate diet prevents microlith formation in young animals and reduces lung injury on the basis of reduction in serum SP-D. The burden of pulmonary calcium deposits in established PAM is also diminished within 4 weeks by a low-phosphate diet challenge. These data support a causative role for Npt2b in the pathogenesis of PAM and the use of the PAM mouse model as a preclinical platform for the development of biomarkers and therapeutic strategies. PMID:26560359

  19. Microtubule plus-end and minus-end capture at adherens junctions is involved in the assembly of apico-basal arrays in polarised epithelial cells.

    Science.gov (United States)

    Bellett, Gemma; Carter, Jane M; Keynton, Jennifer; Goldspink, Deborah; James, Colin; Moss, David K; Mogensen, Mette M

    2009-10-01

    Apico-basal polarisation of epithelial cells involves a dramatic reorganisation of the microtubule cytoskeleton. The classic radial array of microtubules focused on a centrally located centrosome typical of many animal cells is lost or greatly reduced and a non-centrosomal apico-basal array develops. The molecules and mechanisms responsible for the assembly and positioning of these non-centrosomal microtubules have not been fully elucidated. Using a Nocodazole induced regrowth assay in invitro culture (MDCK) and in situ epithelial (cochlear Kolliker's) cell models we establish that the apico-basal array originates from the centrosome and that the non-centrosomal microtubule minus-end anchoring sites do not contribute significantly to their nucleation. Confocal and electron microscopy revealed that an extended radial array assembles with microtubule plus-ends targeting cadheren sites at adherens junctions and EB1 and CLIP-170 co-localising with beta-catenin and dynein clusters at the junction sites. The extended radial array is likely to be a vital intermediate step in the assembly process with cortical anchored dynein providing the mechanical force required for microtubule release, translocation and capture. Ultrastructural analyses of the apico-basal arrays in fully polarised MDCK and Kolliker's cells revealed microtubule minus-end association with the most apical adherens junction (Zonula adherens). We propose that a release and capture model involving both microtubule plus- and minus-end capture at adherens junctions is responsible for the generation of non-centrosomal apico-basal arrays in most centrosome containing polarised epithelial cells. PMID:19479825

  20. Protein profile of basal prostate epithelial progenitor cells-stage-specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo.

    Science.gov (United States)

    Höfner, Thomas; Klein, Corinna; Eisen, Christian; Rigo-Watermeier, Teresa; Haferkamp, Axel; Sprick, Martin R

    2016-04-01

    The long-term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows determining their cell surface phenotype in greater detail. Mouse (Lin(-) Sca-1(+) CD49f(+) Trop2(high) -phenotype) and human (Lin(-) CD49f(+) TROP2(high) ) basal prostate progenitor cells were expanded in vitro. Human and mouse cells were screened using 242 anti-human or 176 antimouse monoclonal antibodies recognizing the cell surface protein profile. Quantitative expression was evaluated at the single-cell level using flow cytometry. Differentially expressed cell surface proteins were evaluated in conjunction with the known CD49f(+) /TROP2(high) phenotype of basal prostate progenitor cells and characterized by in vivo sandwich-transplantation experiments using nude mice. The phenotype of basal prostate progenitor cells was determined as CD9(+) /CD24(+) /CD29(+) /CD44(+) /CD47(+) /CD49f(+) /CD104(+) /CD147(+) /CD326(+) /Trop2(high) of mouse as well as human origin. Our analysis revealed several proteins, such as CD13, Syndecan-1 and stage-specific embryonal antigens (SSEAs), as being differentially expressed on murine and human CD49f(+) TROP2(+) basal prostate progenitor cells. Transplantation experiments suggest that CD49f(+) TROP2(high) SSEA-4(high) human prostate basal progenitor cells to be more potent to regenerate prostate tubules in vivo as compared with CD49f(+) TROP2(high) or CD49f(+) TROP2(high) SSEA-4(low) cells. Determination of the cell surface protein profile of functionally defined murine and human basal prostate progenitor cells reveals differentially expressed proteins that may change the potency and regenerative function of epithelial progenitor cells within the prostate. SSEA-4 is a candidate cell surface marker that putatively enables a more accurate identification of the basal PESC lineage. PMID:26849468

  1. 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

  2. Regulation and function of the two-pore-domain (K2P) potassium channel Trek-1 in alveolar epithelial cells

    OpenAIRE

    Schwingshackl, Andreas; Teng, Bin; Ghosh, Manik; West, Alina Nico; Makena, Patrudu; Gorantla, Vijay; Sinclair, Scott E.; Waters, Christopher M.

    2011-01-01

    Hyperoxia can lead to a myriad of deleterious effects in the lung including epithelial damage and diffuse inflammation. The specific mechanisms by which hyperoxia promotes these pathological changes are not completely understood. Activation of ion channels has been proposed as one of the mechanisms required for cell activation and mediator secretion. The two-pore-domain K+ channel (K2P) Trek-1 has recently been described in lung epithelial cells, but its function remains elusive. In this stud...

  3. Fas Activation in Alveolar Epithelial Cells Induces KC (CXCL1) Release by a MyD88-Dependent Mechanism

    OpenAIRE

    Farnand, Alex W.; Eastman, Alison J.; Herrero, Raquel; Hanson, Josiah F.; Mongovin, Steve; Altemeier, William A.; Matute-Bello, Gustavo

    2011-01-01

    Activation of the Fas/Fas ligand (FasL) system is associated with activation of apoptotic and proinflammatory pathways that lead to the development of acute lung injury. Previous studies in chimeric mice and macrophage-depleted mice suggested that the main effector cell in Fas-mediated lung injury is not a myeloid cell, but likely an epithelial cell. The goal of this study was to determine whether epithelial cells release proinflammatory cytokines after Fas activation, and to identify the rel...

  4. In vivo autoradiographic demonstration of β-adrenergic binding sites in adult rat type II alveolar epithelial cells

    International Nuclear Information System (INIS)

    Adult male rats were injected intravenously with the muscarinic binding probe 3H-Quinuclidinyl benzilate (QNB) or the β-adrenergic probe 3H-dihydroalprenolol (DHA). Other rats were pre-treated with an intraperitoneal injection of a 500-fold excess of L-isoproterenol prior to the DHA. Light microscopic autoradiography of 0.5 μm sections of lung from the QNB group demonstrated very little labelling even after 6 months of exposure. In constrast, trachealis smooth muscle from these animals contained substantial labelling. Autoradiographs of lung from rats injected with DHA demonstrated labelling which was well localized over alveolar septa and concentrated over the cytoplasm of type II cells. Quantitative analysis of labelling in the DHA groups indicated a significant reduction of labelling in animals treated with L-isoproterenol prior to DHA, in both the alveolar parenchyma in general and over type II cells. The results of this study provide morphologic evidence for the uptake and specific binding of β-adrenergic antagonists by the adult lung in vivo, while failing to demonstrate similar binding of a muscarinic probe. In addition, the results demonstrate specific β-adrenergic receptors on type II cells in vivo and substantiate the view of a direct effect of β-adrenergic agonists on alveolar type II cells

  5. Oncostatin M, but not interleukin-6 or leukemia inhibitory factor, stimulates expression of alpha1-proteinase inhibitor in A549 human alveolar epithelial cells.

    Science.gov (United States)

    Sallenave, J M; Tremblay, G M; Gauldie, J; Richards, C D

    1997-06-01

    Alpha-1 proteinase inhibitor (A1-Pi) is the main serine proteinase inhibitor found in human plasma and is a potent elastase inhibitor in various tissues, including lung. A1-Pi is expressed and induced in liver during inflammatory responses but can also be produced by epithelial cells. Since hepatocyte A1-Pi production is stimulated by interleukin-6 (IL-6) and other gp130-cytokines, such as leukemia inhibitory factor (LIF) and oncostatin M (OM), we investigated the role of these cytokines in regulating A1-Pi in lung epithelial cells. We show that OM, a monocyte and T cell product, can specifically and potently induce A1-Pi production in lung-derived A549 alveolar (epithelial) cells, as well as in liver-derived HepG2 cells. Both A1-Pi protein (as detected by ELISA and Western blots) and mRNA levels were enhanced 20-fold to 30-fold in A549 cells. OM was also able to stimulate the expression of tissue inhibitor of metalloproteinase-1 in these cells. Interestingly, other members of the IL-6 family (IL-6 and LIF) had little or no effect on A549 cells, and proinflammatory cytokines, such as IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) also had no stimulatory effect on A1-Pi synthesis in A549 cells. Costimulation with IL-1 beta resulted in a decrease in A1-Pi production from OM-stimulated A549 cells. However, IL-6 production was synergistically enhanced. OM was also able to stimulate A1-Pi production from a bronchial epithelial primary cell line, whereas an intestinal epithelial cell line HT29 responded to IL-6 but not OM. These results suggest that lung levels A1-Pi could be derived not only from liver and inflammatory cells but also from epithelial cells, which can be upregulated on stimulation by OM. This may have implications for regulation of local activity of human neutrophil elastase (HNE) in such diseases as emphysema and cystic fibrosis. PMID:9198001

  6. 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

  7. Nemo-like kinase regulates the expression of vascular endothelial growth factor (VEGF) in alveolar epithelial cells.

    Science.gov (United States)

    Ke, Hengning; Masoumi, Katarzyna Chmielarska; Ahlqvist, Kristofer; Seckl, Michael J; Rydell-Törmänen, Kristina; Massoumi, Ramin

    2016-01-01

    The canonical Wnt signaling can be silenced either through β-catenin-mediated ubiquitination and degradation or through phosphorylation of Tcf and Lef by nemo-like kinase (NLK). In the present study, we generated NLK deficient animals and found that these mice become cyanotic shortly before death because of lung maturation defects. NLK-/- lungs exhibited smaller and compressed alveoli and the mesenchyme remained thick and hyperplastic. This phenotype was caused by epithelial activation of vascular endothelial growth factor (VEGF) via recruitment of Lef1 to the promoter of VEGF. Elevated expression of VEGF and activation of the VEGF receptor through phosphorylation promoted an increase in the proliferation rate of epithelial and endothelial cells. In summary, our study identifies NLK as a novel signaling molecule for proper lung development through the interconnection between epithelial and endothelial cells during lung morphogenesis. PMID:27035511

  8. 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

  9. Potential in vitro model for testing the effect of exposure to nanoparticles on the lung alveolar epithelial barrier

    Directory of Open Access Journals (Sweden)

    Raymond Derk

    2015-03-01

    Full Text Available Pulmonary barrier function plays a pivotal role in protection from inhaled particles. However, some nano-scaled particles, such as carbon nanotubes (CNT, have demonstrated the ability to penetrate this barrier in animal models, resulting in an unusual, rapid interstitial fibrosis. To delineate the underlying mechanism and specific bio-effect of inhaled nanoparticles in respiratory toxicity, models of lung epithelial barriers are required that allow accurate representation of in vivo systems; however, there is currently a lack of consistent methods to do so. Thus, this work demonstrates a well-characterized in vitro model of pulmonary barrier function using Calu-3 cells, and provides the experimental conditions required for achieving tight junction complexes in cell culture, with trans-epithelial electrical resistance measurement used as a biosensor for proper barrier formation and integrity. The effects of cell number and serum constituents have been examined and we found that changes in each of these parameters can greatly affect barrier formation. Our data demonstrate that use of 5.0 × 104 Calu-3 cells/well in the Transwell cell culture system, with 10% serum concentrations in culture media is optimal for assessing epithelial barrier function. In addition, we have utilized CNT exposure to analyze the dose-, time-, and nanoparticle property-dependent alterations of epithelial barrier permeability as a means to validate this model. Such high throughput in vitro cell models of the epithelium could be used to predict the interaction of other nanoparticles with lung epithelial barriers to mimic respiratory behavior in vivo, thus providing essential tools and bio-sensing techniques that can be uniformly employed.

  10. Intracellular accumulation dynamics and fate of zinc ions in alveolar epithelial cells exposed to airborne ZnO nanoparticles at the air-liquid interface

    Energy Technology Data Exchange (ETDEWEB)

    Mihai, Cosmin; Chrisler, William B.; Xie, Yumei; Hu, Dehong; Szymanski, Craig J.; Tolic, Ana; Klein, Jessica; Smith, Jordan N.; Tarasevich, Barbara J.; Orr, Galya

    2015-02-01

    Airborne nanoparticles (NPs) that enter the respiratory tract are likely to reach the alveolar region. Accumulating observations support a role for zinc oxide (ZnO) NP dissolution in toxicity, but the majority of in vitro studies were conducted in cells exposed to NPs in growth media, where large doses of dissolved ions are shed into the exposure solution. To determine the precise intracellular accumulation dynamics and fate of zinc ions (Zn2+) shed by airborne NPs in the cellular environment, we exposed alveolar epithelial cells to aerosolized NPs at the air-liquid interface (ALI). Using a fluorescent indicator for Zn2+, together with organelle-specific fluorescent proteins, we quantified Zn2+ in single cells and organelles over time. We found that at the ALI, intracellular Zn2+ values peaked 3 h post exposure and decayed to normal values by 12 h, while in submersed cultures, intracellular Zn2+ values continued to increase over time. The lowest toxic NP dose at the ALI generated peak intracellular Zn2+ values that were nearly 3 folds lower than the peak values generated by the lowest toxic dose of NPs in submersed cultures, and 8 folds lower than the peak values generated by the lowest toxic dose of ZnSO4 or Zn2+. At the ALI, the majority of intracellular Zn2+ was found in endosomes and lysosomes as early as 1 h post exposure. In contrast, the majority of intracellular Zn2+ following exposures to ZnSO4 was found in other larger vesicles, with less than 10% in endosomes and lysosomes. Together, our observations indicate that low but critical levels of intracellular Zn2+ have to be reached, concentrated specifically in endosomes and lysosomes, for toxicity to occur, and point to the focal dissolution of the NPs in the cellular environment and the accumulation of the ions specifically in endosomes and lysosomes as the processes underlying the potent toxicity of airborne ZnO NPs.

  11. Hyperoxia-mediated LC3B activation contributes to the impaired transdifferentiation of type II alveolar epithelial cells (AECIIs) to type I cells (AECIs).

    Science.gov (United States)

    Zhang, Liang; Zhao, Shuang; Yuan, Lijie; Wu, Hongmin; Jiang, Hong; Luo, Gang

    2016-09-01

    Life-saving mechanical ventilation can also cause lung injury through the overproduction of reactive oxygen species (ROS), leading to bronchopulmonary dysplasia (BPD)-like symptoms in preterm infants. It is reported that the autophagic protein microtubule-associated protein-1 light chain (LC)-3B can confer protection against hyperoxia-induced DNA damage in lung alveolar epithelium. However, its role in the transdifferentiation of type II alveolar epithelial cells (AECIIs) to type I cells (AECIs) is unclear and requires further investigation. In this study, newborn Sprague-Dawley rats were exposed to 90% oxygen for up to 14 days to mimic BPD in human infants, with neonatal pups exposed to room air (21% oxygen) as controls. Primary rat AECIIs were cultured under hyperoxic conditions for up to 24 hours to further investigate the underlying mechanisms. This study found that hyperoxia promoted a significant and time-dependent increase of AECII marker surfactant protein (SP)-C in the lung. The increase of AECI marker T1α was repressed by hyperoxia during lung development. These results indicated an impaired AECII transdifferentiation. Pulmonary ROS concentration and expression of autophagic protein LC-3B were increased gradually in response to hyperoxia exposure. Furthermore, AECIIs produced more ROS when cultured under hyperoxic conditions in vitro. Both the LC3B expression and the conversion from LC3BI to LC3BII were enhanced in hyperoxic AECs. Interestingly, inhibition of LC3B either by ROS inhibitor N-acetyl-l-cysteine (NAC) or adenovirus-mediated LC3B shRNA could partly restore AECII transdifferentiation under hyperoxia condition. In summary, the current study reveals a novel role of activated LC3B induced by hyperoxia in AECII transdifferentiation. PMID:27187184

  12. Evaluation of pulmonary alveolar epithelial integrity by the detection of restriction to diffusion of hydrophilic solutes of different molecular sizes.

    Science.gov (United States)

    Mason, G R; Peters, A M; Bagdades, E; Myers, M J; Snook, D; Hughes, J M

    2001-03-01

    The rate of transfer of a hydrophilic solute from the alveoli to pulmonary blood following inhalation as an aerosol depends on the molecular size of the solute and the permeability of the alveolar epithelium. The value of this measurement for assessing damage to the epithelium in lung disease is compromised by cigarette smoking, which accelerates clearance by unknown mechanisms. The rates of clearance of (99m)Tc-labelled diethylenetriaminepenta-acetic acid (DTPA) (molecular mass 492 Da) and (113m)In-labelled biotinylated DTPA (B-DTPA) (molecular mass 1215 Da) were monitored simultaneously by dynamic gamma-radiation camera imaging following simultaneous inhalation, and compared between eight normal non-smoking subjects and nine habitual cigarette smokers. The clearance rates of DTPA were 0.95 (S.D. 0.39)%/min in non-smokers and 4.13 (1.06) %/min in smokers. These were about twice the clearance rates of B-DTPA, which in the corresponding groups were 0.41 (0.26) and 2.12 (0.72)%/min respectively. The ratio of the B-DTPA/DTPA clearance rates was, in all subjects, less than the ratio (0.74) of the cube roots of the molecular masses of the solutes, assumed to correspond to the ratio of their free diffusion coefficients in water, and was not significantly different between smokers and non-smokers. As alveolar permeability increased, the ratio of clearance rates in the entire population showed a significant trend to increase in a non-linear fashion towards the value corresponding to the ratio of the free diffusion coefficients. We conclude that the diffusion of at least the larger of these two solutes through the pulmonary alveolar epithelium is restricted (i.e. associated with a reflection coefficient greater than zero). Cigarette smoking, however, does not appear to cause a loss of this restriction, and may increase solute clearance by other mechanisms, such as reducing fluid volume within the alveolus, thereby raising the local radiotracer concentration, or increasing

  13. Canonical pathways, networks and transcriptional factor regulation by clinical strains of Mycobacterium tuberculosis in pulmonary alveolar epithelial cells.

    Science.gov (United States)

    Mvubu, Nontobeko E; Pillay, Balakrishna; Gamieldien, Junaid; Bishai, William; Pillay, Manormoney

    2016-03-01

    Limited knowledge exists on pathways, networks and transcriptional factors regulated within epithelial cells by diverse Mycobacterium tuberculosis genotypes. This study aimed to elucidate these mechanisms induced in A549 epithelial cells by dominant clinical strains in KwaZulu-Natal, South Africa. RNA for sequencing was extracted from epithelial cells at 48 h post-infection with 5 strains at a multiplicity of infection of approximately 10:1. Bioinformatics analysis performed with the RNA-Seq Tuxedo pipeline identified differentially expressed genes. Changes in pathways, networks and transcriptional factors were identified using Ingenuity Pathway Analysis (IPA). The interferon signalling and hepatic fibrosis/hepatic stellate cell activation pathways were among the top 5 canonical pathways in all strains. Hierarchical clustering for enrichment of cholesterol biosynthesis and immune associated pathways revealed similar patterns for Beijing and Unique; F15/LAM4/KZN and F11; and, F28 and H37Rv strains, respectively. However, the induction of top scoring networks varied among the strains. Among the transcriptional factors, only EHL, IRF7, PML, STAT1, STAT2 and VDR were induced by all clinical strains. Activation of the different pathways, networks and transcriptional factors revealed in the current study may be an underlying mechanism that results in the differential host response by clinical strains of M. tuberculosis. PMID:26980499

  14. Reactive oxygen species mediated DNA damage in human lung alveolar epithelial (A549) cells from exposure to non-cytotoxic MFI-type zeolite nanoparticles.

    Science.gov (United States)

    Bhattacharya, Kunal; Naha, Pratap C; Naydenova, Izabela; Mintova, Svetlana; Byrne, Hugh J

    2012-12-17

    MFI-50 nanoparticles was found to accumulate over a longer period of time as compared to MFI-100 nanoparticles. The study therefore points towards the capability of the non-cytotoxic zeolite nanoparticles to induce oxidative stress resulting in short-term altered cellular metabolism up-regulation and genomic instability. Although the damage was found to be short-lived, its persistence over longer durations, or stabilization cannot be neglected. Further studies are in progress to yield a better understanding of the mechanisms for oxidative stress and resulting cascade of events leading to genetic damage in the human lung alveolar epithelial cells following exposure to zeolite nanoparticles of different sizes. PMID:23103338

  15. Basal and copper-induced expression of metallothionein isoform 1,2 and 3 genes in epithelial cancer cells: The role of tumor suppressor p53.

    Science.gov (United States)

    Ostrakhovitch, E A; Song, Y P; Cherian, M G

    2016-05-01

    Metallothioneins (MTs) are a ubiquitous low-molecular weight, cysteine rich proteins with a high affinity for metal ions. The expression and induction of MTs have been associated with protection against DNA damage, oxidative stress, and apoptosis. Our past research had shown that p53 is an important factor in metal regulation of MTs. The present study was undertaken to explore further the interrelationship between p53 and MTs. We investigated whether silencing of p53 could affect expression pattern of basal and copper induced metallothioneins. The silencing of wild-type p53 (wt-p53) in epithelial breast cancer MCF7 cells affected the basal level of MT-2A RNA, whereas the levels of MT-1A and MT-1X RNA remained largely unchanged. The expression of MT-3 was undetectable in MCF7 with either functional or silenced p53. MCF7 cells with silenced wt-p53 failed to upregulate MT-2A in response to copper and showed a reduced sensitivity toward copper induced cell apoptotic death. Similarly in MCF7-E6 and MDA-MB-231 cells, the presence of inactive/mutated p53 halted MT-1A and MT-2A gene expression in response to copper. Constitutive expression of MT-3 RNA was detectable in the presence of mutated p53 (mtp53). Transient transfection of MDA-MB-231 cells with wt-p53 enabled copper induced upregulation of both MT-1A and MT-2A but not basal level of MT-2A, MT-1E, MT-1X and MT-3. Inactivation of p53 in HepG2 cells amplified the basal expression of studied MT isoforms, including MT-3, as well as copper-induced mRNA expression of MTs except MT-1H and MT-3. Presented data demonstrate a direct relation between p53 and MT-1A and MT-2A and they also indicate that wt-p53 might be a negative regulator of MT-3 in epithelial cancer cells. PMID:27049123

  16. Human neutrophil elastase regulates the expression and secretion of elafin (elastase-specific inhibitor) in type II alveolar epithelial cells.

    Science.gov (United States)

    Reid, P T; Marsden, M E; Cunningham, G A; Haslett, C; Sallenave, J M

    1999-08-20

    Elafin is a low molecular weight antiproteinase believed to be important in the regulation of elastase mediated tissue damage. The expression of elafin is known to be regulated by proinflammatory cytokines such as interleukin-1 beta and tumour necrosis factor but little was known regarding the effect of human neutrophil elastase (HNE). Employing a chloramphenicol acetyltransferase reporter construct of the human elafin gene, reverse transcription PCR from total cellular RNA and ELISA techniques, we have examined the effect of human neutrophil elastase on the transcription and secretion of human elafin in the pulmonary epithelial A549 cell line. Stimulation with HNE at concentrations of 10(-10) and 10(-11) M resulted in a significant upregulation of elafin promoter activity. Similarly, transcription of the endogenous human elafin gene was upregulated with HNE concentrations ranging from 10(-10) to 10(-12) M. In addition, we demonstrate that stimulation with HNE at concentrations ranging from 10(-9) and 10(-12) M resulted in a significant reduction in the secreted elafin protein as measured in the cell supernatant. These results provide further evidence for a role of elafin in the regulation of HNE driven proteolysis of the extracellular matrix. PMID:10486558

  17. 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

  18. A Novel Approach for Ovine Primary Alveolar Epithelial Type II Cell Isolation and Culture from Fresh and Cryopreserved Tissue Obtained from Premature and Juvenile Animals.

    Directory of Open Access Journals (Sweden)

    Mariola M Marcinkiewicz

    Full Text Available The in vivo ovine model provides a clinically relevant platform to study cardiopulmonary mechanisms and treatments of disease; however, a robust ovine primary alveolar epithelial type II (ATII cell culture model is lacking. The objective of this study was to develop and optimize ovine lung tissue cryopreservation and primary ATII cell culture methodologies for the purposes of dissecting mechanisms at the cellular level to elucidate responses observed in vivo. To address this, we established in vitro submerged and air-liquid interface cultures of primary ovine ATII cells isolated from fresh or cryopreserved lung tissues obtained from mechanically ventilated sheep (128 days gestation-6 months of age. Presence, abundance, and mRNA expression of surfactant proteins was assessed by immunocytochemistry, Western Blot, and quantitative PCR respectively on the day of isolation, and throughout the 7 day cell culture study period. All biomarkers were significantly greater from cells isolated from fresh than cryopreserved tissue, and those cultured in air-liquid interface as compared to submerged culture conditions at all time points. Surfactant protein expression remained in the air-liquid interface culture system while that of cells cultured in the submerged system dissipated over time. Despite differences in biomarker magnitude between cells isolated from fresh and cryopreserved tissue, cells isolated from cryopreserved tissue remained metabolically active and demonstrated a similar response as cells from fresh tissue through 72 hr period of hyperoxia. These data demonstrate a cell culture methodology using fresh or cryopreserved tissue to support study of ovine primary ATII cell function and responses, to support expanded use of biobanked tissues, and to further understanding of mechanisms that contribute to in vivo function of the lung.

  19. A Novel Approach for Ovine Primary Alveolar Epithelial Type II Cell Isolation and Culture from Fresh and Cryopreserved Tissue Obtained from Premature and Juvenile Animals.

    Science.gov (United States)

    Marcinkiewicz, Mariola M; Baker, Sandy T; Wu, Jichuan; Hubert, Terrence L; Wolfson, Marla R

    2016-01-01

    The in vivo ovine model provides a clinically relevant platform to study cardiopulmonary mechanisms and treatments of disease; however, a robust ovine primary alveolar epithelial type II (ATII) cell culture model is lacking. The objective of this study was to develop and optimize ovine lung tissue cryopreservation and primary ATII cell culture methodologies for the purposes of dissecting mechanisms at the cellular level to elucidate responses observed in vivo. To address this, we established in vitro submerged and air-liquid interface cultures of primary ovine ATII cells isolated from fresh or cryopreserved lung tissues obtained from mechanically ventilated sheep (128 days gestation-6 months of age). Presence, abundance, and mRNA expression of surfactant proteins was assessed by immunocytochemistry, Western Blot, and quantitative PCR respectively on the day of isolation, and throughout the 7 day cell culture study period. All biomarkers were significantly greater from cells isolated from fresh than cryopreserved tissue, and those cultured in air-liquid interface as compared to submerged culture conditions at all time points. Surfactant protein expression remained in the air-liquid interface culture system while that of cells cultured in the submerged system dissipated over time. Despite differences in biomarker magnitude between cells isolated from fresh and cryopreserved tissue, cells isolated from cryopreserved tissue remained metabolically active and demonstrated a similar response as cells from fresh tissue through 72 hr period of hyperoxia. These data demonstrate a cell culture methodology using fresh or cryopreserved tissue to support study of ovine primary ATII cell function and responses, to support expanded use of biobanked tissues, and to further understanding of mechanisms that contribute to in vivo function of the lung. PMID:26999050

  20. Multiple roles for keratin intermediate filaments in the regulation of epithelial barrier function and apico-basal polarity.

    Science.gov (United States)

    Salas, Pedro J; Forteza, Radia; Mashukova, Anastasia

    2016-01-01

    As multicellular organisms evolved a family of cytoskeletal proteins, the keratins (types I and II) expressed in epithelial cells diversified in more than 20 genes in vertebrates. There is no question that keratin filaments confer mechanical stiffness to cells. However, such a number of genes can hardly be explained by evolutionary advantages in mechanical features. The use of transgenic mouse models has revealed unexpected functional relationships between keratin intermediate filaments and intracellular signaling. Accordingly, loss of keratins or mutations in keratins that cause or predispose to human diseases, result in increased sensitivity to apoptosis, regulation of innate immunity, permeabilization of tight junctions, and mistargeting of apical proteins in different epithelia. Precise mechanistic explanations for these phenomena are still lacking. However, immobilization of membrane or cytoplasmic proteins, including chaperones, on intermediate filaments ("scaffolding") appear as common molecular mechanisms and may explain the need for so many different keratin genes in vertebrates. PMID:27583190

  1. Measurement of Regional and Global Pulmonary Clearance of 99mTc-DTPA (Demethylamitriptylene-Acetate): An Index of Alveolar Epithelial Permeability

    International Nuclear Information System (INIS)

    The main purpose of this study has been introduction of a new method for alveoli-capillary permeability evaluation. Many reports pointed out to the altered transit of soluble particles through this barrier. From pathophysiological aspect the main interest is the elucidation of permeability's alteration in different pulmonary pathology. We decided to use for lung epithelial permeability measurements 99mTc-DTPA inhaled aerosols and sequential assessment of its lung clearance. The aerosols were obtained using oxygen flow nebulizers with aerosols' generators Ultra Vent (Malinkrodt) and Venticis II (CIS bio international) that enabled as to get submicron particles. Oxygen flow between 9 and 11 liters per minute was used. Optimum images were obtained with 1480 MBq of inhaled aerosols at least 2 to 3 minutes. DTPA that was used for aerosols labeling had been produced in our Department and the results were compared with DTPA provided by CIS bio international. High correlation between both agents was proven. During the whole study ex tamper prepared radiopharmaceuticals were used and quality control was done using paper chromatography method. Acquisition was done in sitting position with gamma camera interfaced to a ADAC and Scintiview. The measurements lasted for 20 minutes. Data were stored on 64x64 matrices. Regions of interest over both lungs were drown and each one was divided in three segments: apical, medial, and basal. Using computer program curves of 99mTc-DTPA lung clearance were derived. From the obtained time activity curves half-time of the global and the regional lung clearance was assessed. In the control group comprised of 32 healthy volunteers (non-smokers) we had got values, used after works as reference range. Our normal values for global clearance are: 68±5,5 min. for left whole lung, 68,1±6,5 min for right whole lung, and 49±7,7 min for apical, 66,9±8 min for middle, and 75,9±6,4 min basal regional lung clearance, and they are in keeping with the

  2. 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....

  3. 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...

  4. Low Trichorhinophalangeal Syndrome 1 Gene Transcript Levels in Basal-like Breast Cancer Associate with Mesenchymal-to-epithelial Transition

    Institute of Scientific and Technical Information of China (English)

    Yi Bao; Ling-juan Ruan; Juan-fen Mo

    2013-01-01

    Objective To investigate trichorhinophalangeal syndrome 1 gene (TRPS-1) expression patterns in different subtypes of breast cancer and its correlations with other genes and survival using microarray data sets. Methods The transcripts of TRPS-1 and its role in survival in breast cancer were analyzed using published microarray data sets-Netherlands Cancer Institute (NKI) cohort andWang cohort. Results TRPS-1 expression was lower in basal-like breast cancer. The mRNA levels of TRPS-1 negatively correlated with Slug (Pearson correlation coefficient=−0.1366, P=0.0189 in NKI data set and Pearson correlation coefficient=−0.1571, P=0.0078 in Wang data set), FOXC1 (Pearson correlation coefficient=−0.1211, P=0.0376 in NKI data set and Pearson correlation coefficient=−0.1709, P=0.0037 in Wang data set), and CXCL1 (Pearson correlation coefficient=−0.1197, P=0.0399 in NKI data set and Pearson correlation coefficient=−0.3436, P Conclusion The strong expression of TRPS-1 may serve as a good prognostic marker in breast cancer.

  5. 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...

  6. 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

  7. 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...

  8. Abberent expression of oncogenic and tumor-suppressive microRNAs and their target genes in human adenocarcinoma alveolar basal epithelial cells

    Directory of Open Access Journals (Sweden)

    Elham Tafsiri

    2016-01-01

    Conclusion: The significant differential expression level of these miRNAs made them as candidate biomarkers in NSCLC tumor tissues of patients. Perhaps Bcl-2 down-regulation and Akt-3 up-regulation can be linked with survival signals in A549 cell line. We can conclude that Bcl-2 and Akt-3 might be therapeutic targets to inhibit cell proliferation in NSCLC.

  9. Epithelial hyperplasia, alveoli —

    Science.gov (United States)

    Solitary or multiple foci of increased cellularity distal to terminal bronchioles. The background of broncho-alveolar architecture remains detectable, and epithelial cells are usually single layered. Round to oval hypertrophic type II pneumocytes with abundant eosinophilic cytoplasm line alveolar walls. In bronchiolar subvariant, also called bronchiolization of alveoli, alveolar walls are lined by cuboidal to columnar cells with features of bronchiolar differentiation, such as formation of cilia, Clara cell resemblance, and presence of mucous granules. Foci of consolidation may indicate early stages of adenoma formation. Macrophages may be present in the alveolar lumens.

  10. Lipoteichoic acid induces surfactant protein-A biosynthesis in human alveolar type II epithelial cells through activating the MEK1/2-ERK1/2-NF-κB pathway

    Directory of Open Access Journals (Sweden)

    Liu Feng-Lin

    2012-10-01

    Full Text Available Abstract Background Lipoteichoic acid (LTA, a gram-positive bacterial outer membrane component, can cause septic shock. Our previous studies showed that the gram-negative endotoxin, lipopolysaccharide (LPS, could induce surfactant protein-A (SP-A production in human alveolar epithelial (A549 cells. Objectives In this study, we further evaluated the effect of LTA on SP-A biosynthesis and its possible signal-transducing mechanisms. Methods A549 cells were exposed to LTA. Levels of SP-A, nuclear factor (NF-κB, extracellular signal-regulated kinase 1/2 (ERK1/2, and mitogen-activated/extracellular signal-regulated kinase kinase (MEK1 were determined. Results Exposure of A549 cells to 10, 30, and 50 μg/ml LTA for 24 h did not affect cell viability. Meanwhile, when exposed to 30 μg/ml LTA for 1, 6, and 24 h, the biosynthesis of SP-A mRNA and protein in A549 cells significantly increased. As to the mechanism, LTA enhanced cytosolic and nuclear NF-κB levels in time-dependent manners. Pretreatment with BAY 11–7082, an inhibitor of NF-κB activation, significantly inhibited LTA-induced SP-A mRNA expression. Sequentially, LTA time-dependently augmented phosphorylation of ERK1/2. In addition, levels of phosphorylated MEK1 were augmented following treatment with LTA. Conclusions Therefore, this study showed that LTA can increase SP-A synthesis in human alveolar type II epithelial cells through sequentially activating the MEK1-ERK1/2-NF-κB-dependent pathway.

  11. Transgenic mice exhibiting inducible and spontaneous Cre activities driven by a bovine keratin 5 promoter that can be used for the conditional analysis of basal epithelial cells in multiple organs

    Directory of Open Access Journals (Sweden)

    Liang Chih-Chia

    2009-01-01

    Full Text Available Abstract Background Cre/loxP-mediated genetic modification is the most widely used conditional genetic approach used in the mouse. Engineered Cre and the mutated ligand-binding domain of estrogen receptor fusion recombinase (CreERT allow temporal control of Cre activity. Results In this study, we have generated two distinct transgenic mouse lines expressing CreERT, which show 4-hydroxytamoxifen (4-OHT-inducible and spontaneous (4-OHT-independent Cre activities, referred to Tg(BK5-CreERTI and Tg(BK5-CreERTS, respectively. The transgenic construct is driven by the bovine Keratin 5 promoter, which is active in the basal epithelial lineage of stratified and pseudo-stratified epithelium across multiple organs. Despite the difference in 4-OHT dependency, the Tg(BK5-CreERTI and Tg(BK5-CreERTS mouse lines shared similar Cre-mediated recombination among various organs, except for unique mammary epithelial Cre activity in Tg(BK5-CreERTS females. Conclusion These two new transgenic mouse lines for the analysis of basal epithelial function and for the genetic modification have been created allowing the identification of these cell lineages and analysis of their differentiation during embryogenesis, during perinatal development and in adult mice.

  12. 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

  13. Protective effect of Ac-SDKP on alveolar epithelial cells through inhibition of EMT via TGF-β1/ROCK1 pathway in silicosis in rat.

    Science.gov (United States)

    Deng, Haijing; Xu, Hong; Zhang, Xianghong; Sun, Yue; Wang, Ruimin; Brann, Darrell; Yang, Fang

    2016-03-01

    The epithelial-mesenchymal transition (EMT) is a critical stage during the development of silicosis fibrosis. In the current study, we hypothesized that the anti-fibrotic tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) may exert its anti-fibrotic effects via activation of the TGF-β1/ROCK1 pathway, leading to inhibition of EMT. To address this hypothesis, we first examined the effect of Ac-SDKP upon EMT using an in vivo rat silicosis model, as well as in an in vitro model of TGF-β1-induced EMT. Confocal laser scanning microscopy was used to examine colocalization of surfactant protein A (SP-A), fibroblast specific protein-1 (FSP-1) and α-smooth muscle actin (α-SMA) in vivo. Western blot analysis was used to examine for changes in the protein levels of E-cadherin (E-cad) and SP-A (epithelial cell markers), vimentin (mesenchymal cell marker), α-SMA (active myofibroblast marker), and collagen I and III in both in vivo and in vitro experiments. Secondly, we utilized Western blot analysis and confocal laser scanning microscopy to examine the protein expression of TGF-β1 and ROCK1 in in vivo and in vitro studies. The results revealed that Ac-SDKP treatment prevented increases in the expression of mesenchymal markers as well as TGF-β1, ROCK1, collagen I and III. Furthermore, Ac-SDKP treatment prevented decreases in the expression of epithelial cell markers in both in vivo and in vitro experiments. Based on the results, we conclude that Ac-SDKP inhibits the transition of epithelial cell-myofibroblast in silicosis via activation of the TGF-β1/ROCK1 signaling pathway, which may serve as a novel mechanism by which it exerts its anti-fibrosis properties. PMID:26785300

  14. 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.

  15. 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, ...

  16. Src激酶在机械通气性牵张致肺泡上皮细胞损伤中的作用%Role of Src tyrosine kinase in damage to alveolar epithelial cells caused by mechanical stretch

    Institute of Scientific and Technical Information of China (English)

    赵涛; 刘孟洁; 谷长平; 王月兰

    2014-01-01

    Objective To evaluate the role of Src tyrosine kinase in damage to alveolar epithelial cells caused by mechanical stretch.Methods MLE-12 cells cultured in vitro were randomly divided into 3 groups using a random number table:mechanical stretch group (group S),dimethyl sulfoxide control group (group D),and Src tyrosine kinase inhibitor PP2 group (group P).In D and P groups,dimethyl sulfoxide 30 μl/ml and PP2 100 μmol/L were added to the culture medium,respectively,and the cells were then cultured for 30 min.The cells underwent mechanical stretch for 8 h with frequency of0.5 Hz and amplitude of 20% in the three groups.At 0,2,4 and 8 h of mechanical stretch,MLE-12 cells in 3 wells of each group were collected for determination of cell apoptosis with flow cytometry and expression of occludin using Western blot.The apoptosis rate was calculated.Results Compared with S group,no significant changes were found in the apoptosis rate and expression of occludin at each time point in group D,and the apoptosis rate was significantly decreased,and the expression of occludin was up-regulated at 2,4 and 8 h of mechanical stretch in group P.Conclusion The activation of Src tyrosine kinase is involved in damage to alveolar epithelial cells caused by mechanical stretch.%目的 评价Src激酶在机械通气性牵张致肺泡上皮细胞损伤中的作用.方法 采用随机数字表法,将体外培养的MEL12细胞分为3组:机械通气性牵张组(S组)、二甲基亚砜对照组(D组)和Src激酶抑制剂PP2组(P组).D组和P组分别加入二甲基亚砜30 μl/ml和Src激酶抑制剂PP2100 μmol/L(用二甲基亚砜溶解)孵育30 min,然后3组给予20%应变率的机械牵张,频率0.5 Hz.分别于机械牵张即刻、2、4和8h时,每组取3孔 MLE-12细胞,测定细胞凋亡情况,计算细胞凋亡率,采用Western blot法测定Occludin蛋白的表达.结果 与S组比较,D组各时点细胞凋亡率和Occludin蛋白表达差异无统计学意义(P>0.05),P

  17. 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...

  18. Effect of Napsin A transfection into type Ⅱ alveolar epithelial cells on pulmonary fibrosis%Ⅱ型肺泡上皮细胞转染Napsin A基因对肺纤维化的干预作用

    Institute of Scientific and Technical Information of China (English)

    郑金旭; 管淑红; 许清; 汤艳; 刘继柱; 吕晓婷

    2010-01-01

    信号传导通路有关.%Objective To study the in vitro effect and mechanism of Napsin A gene transfection into type Ⅱ alveolar epithelial cells on pulmonary fibrosis. Methods A recombinant lentiviral plasmid PLJM1Napsin A was constructed and transfected into human type Ⅱ alveolar epithelial cell line A549. The model of pulmonary fibrosis was established by the in vitro stimulation of A549 cells by transforming growth factor beta-1 (TGF-β1). The morphological changes were observed continuously under inverted microscopy. The proliferation of transgenic and non-transgenic cells was detected by MTT. To observe the degree of epithelialmesenchymal transition ( EMT ) by TGF-β1 intervening A549 cells, the expressions of E-cadherin and fibronectin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.Lastly the protein expression of focal adhesion kinase (FAK) was detected by Western blot to investigate the mechanism. Results The result of sequencing the recombinant lentiviral plasmid PLJM1-Napsin A was the same as the design sequence. Napsin A mRNA and protein were expressed in transgenic A549 cells( P <0. 01 ). The model of pulmonary fibrosis was established successfully based on the morphology of transformed interstitial cell. As compared with the control group, the proliferation rate of transgenic cells decreased significantly (P <0. 05 ). The mRNA and protein expression of E-cadherin significantly decreased in the model of pulmonary fibrosis ( P < 0. 01 ), while the expression of fibronectin markedly increased ( P < 0. 01 ).But the change rate of transgenic cells decreased ( P < 0. 01, P < 0. 05 ). The expression of FAK was significantly elevated after the stimulation of TGF-β1 ( P < 0. 01 ). But the upward trend of the transgenic cells was smaller as compared with the control group (P < 0. 01 ). Conclusion Pulmonary fibrosis may be suppressed by the transfection of Napsin A gene into type Ⅱ alveolar epithelial cells. And the mechanism may

  19. 高氧及TGF-β1对肺泡Ⅱ型细胞上皮间质转化的影响%Effect of hyperoxia and TGF-β1 on epithelial-mesenchymal transition of type Ⅱ alveolar epithelial cells

    Institute of Scientific and Technical Information of China (English)

    刘芳君; 邓春; 郭春宝; 符州

    2012-01-01

    AIM: To investigate the effect of hyperoxia and TGF-pi on epithelial-mesenchymal transition (EMT)of type II alveolar epithelial cells (AEC-Ⅱ ) of mice. METHODS; AEC-Ⅱ cells (MLE-12 lines) were randomly divided into following groups: air exposure group, hyperoxia exposure group, air exposure combined with TGF-pi treatment group, hyperoxia exposure combined with TGF-pi treatment group. The morphological changes of cells in each group were observed at 6, 12, 24, 48 hours. The protein and mR-NA expressions of AEC Ⅱ specific marker lung surfactant protein B ( SP-B) and fibroblast specific marker fibroblast specific protein ( FSP1) were detected by double-labeled immunoflu orescence and real time-PCR at the same time point, respectively. RESULTS: Along with the time of exposure to hyperoxia and TGF-pi, AEC Ⅱ cells gradually changed from pebble-like shape to spindle shape, and showed some fibroblast appearances. Synchronously, the protein expression of SP-B in AEC Ⅱ cells decreased, whereas the expression of FSP1 increased. The co-expressed were observed at 24 hours. Comparing with that of the air exposure group, the mRNA expression of SP-B in the hyperoxia exposure group, air exposure combined with TGF-pi treatment group, hyperoxia exposure combined with TGF-pi treatment group decreaseed significantly, whereas the mRNA expression of FSPl increased significantly at 24 hours and 48 hours (P<0.01). CONCLUSION; Hyperoxia and TGF-β1 can induce EMT of type II alveolar epithelial cells in a time-dependent manner.%目的:探讨高氧及TGF-β1干预小鼠肺泡Ⅱ型细胞(AECⅡ)后,是否发生上皮间质转化(EMT)及其影响.方法:小鼠肺泡Ⅱ型细胞系MLE-12,随机分为空气暴露组、高氧暴露组、TGF-β1干预空气暴露组、TGF-β1干预高氧暴露组.观察各组6、12、24、48 h细胞形态变化.应用细胞免疫荧光双标法及荧光定量PCR法检测各组各时间点肺表面活性物质B (SP-B)及成纤维细胞特异性蛋白1(FSP

  20. 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...

  1. Apico-basal polarity complex and cancer

    Indian Academy of Sciences (India)

    Mohammed Khursheed; Murali Dharan Bashyam

    2014-03-01

    Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is maintained by three well-conserved polarity complexes, namely, PAR, Crumbs and SCRIB. The location and interaction between the components of these complexes defines distinct structural domains of epithelial cells. Establishment and maintenance of apico-basal polarity is regulated through various conserved cell signalling pathways including TGF, Integrin and WNT signalling. Loss of cell polarity is a hallmark for carcinoma, and its underlying molecular mechanism is beginning to emerge from studies on model organisms and cancer cell lines. Moreover, deregulated expression of apico-basal polarity complex components has been reported in human tumours. In this review, we provide an overview of the apico-basal polarity complexes and their regulation, their role in cell migration, and finally their involvement in carcinogenesis.

  2. Isolation and Culture of Human Alveolar Type II Pneumocytes.

    Science.gov (United States)

    Witherden, I R; Tetley, T D

    2001-01-01

    Alveolar type II pneumocytes (alveolar type II cells; TII cells) play an important role in the homeostasis of the alveolar unit. They are the progenitor cells to the type I pneumocyte and are therefore responsible for regeneration of alveolar epithelium following alveolar epithelial cell damage. The type I cell covers over 90% of the alveolar surface, reflecting its capacity to stretch into a flattened cell with very little depth (approx. 0.1 µm), but with a large surface area, to facilitate gas exchange. Nevertheless, the type II cell outnumbers type I cells, estimated to be by 2:1 in rodents. Most of the type II cell lies buried in the interstitium of the alveolus, with only the apical tip of the cell reaching into the airspace, through which another crucial function, provision of alveolar surfactant, occurs. Surfactant synthesis and secretion is a unique feature of type II cells; surfactant consists of a high proportion of phospholipids (approx. 90%) and a small proportion of protein (approx. 10%), which contains surfactant apoprotein (SP), of which four have so far been described, SP-A, SP-B, SP-C, and SP-D (1,2). Surfactant is highly surface active and is essential to prevent alveolar collapse. In addition, surfactant has many other roles, including pulmonary host defense. Compromised surfactant synthesis and function are believed to be a feature of numerous disease states (1,2), including infant respiratory distress syndrome, adult respiratory distress syndrome, alveolar proteinosis, and microbial infection. PMID:21336897

  3. 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.

  4. Phagocytic properties of lung alveolar wall cells

    Directory of Open Access Journals (Sweden)

    Tanaka,Akisuke

    1974-04-01

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

  5. Repopulation of denuded tracheal grafts with alveolar type II cells

    International Nuclear Information System (INIS)

    Repopulation of denuded heterotopic tracheal grafts with populations of specific epithelial cell types is one approach to study the differentiation potential of various cell types. This technique has been adopted to delineate the differentiation pathways of alveolar type II cells isolated from rat lungs. Under the conditions of this experiment, the reestablished epithelial lining was alveolar-like, however, ultrastructural analysis of the cells showed them to be like Clara cells. These preliminary results suggest that the secretary cells of the lung parenchyma and terminal airways may share a common ancestry. (author)

  6. Integrin α6β4 identifies human distal lung epithelial progenitor cells with potential as a cell-based therapy for cystic fibrosis lung disease.

    Directory of Open Access Journals (Sweden)

    Xiaopeng Li

    Full Text Available To develop stem/progenitor cell-based therapy for cystic fibrosis (CF lung disease, it is first necessary to identify markers of human lung epithelial progenitor/stem cells and to better understand the potential for differentiation into distinct lineages. Here we investigated integrin α6β4 as an epithelial progenitor cell marker in the human distal lung. We identified a subpopulation of α6β4(+ cells that localized in distal small airways and alveolar walls and were devoid of pro-surfactant protein C expression. The α6β4(+ epithelial cells demonstrated key properties of stem cells ex vivo as compared to α6β4(- epithelial cells, including higher colony forming efficiency, expression of stem cell-specific transcription factor Nanog, and the potential to differentiate into multiple distinct lineages including basal and Clara cells. Co-culture of α6β4(+ epithelial cells with endothelial cells enhanced proliferation. We identified a subset of adeno-associated virus (AAVs serotypes, AAV2 and AAV8, capable of transducing α6β4(+ cells. In addition, reconstitution of bronchi epithelial cells from CF patients with only 5% normal α6β4(+ epithelial cells significantly rescued defects in Cl(- transport. Therefore, targeting the α6β4(+ epithelial population via either gene delivery or progenitor cell-based reconstitution represents a potential new strategy to treat CF lung disease.

  7. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane

    Energy Technology Data Exchange (ETDEWEB)

    BARCELLOS-HOFF, M. H; AGGELER, J.; RAM, T. G; BISSELL, M. J

    1989-02-01

    An essential feature of mammary gland differentiation during pregnancy is the formation of alveoli composed of polarized epithelial cells, which, under the influence of lactogenic hormones, secrete vectorially and sequester milk proteins. Previous culture studies have described either organization of cells polarized towards lumina containing little or no demonstrable tissue-specific protein, or establishment of functional secretory cells exhibiting little or no glandular architecture. In this paper, we report that tissue-specific vectorial secretion coincides with the formation of functional alveoli-like structures by primary mammary epithelial cells cultured on a reconstituted basement membrane matrix (derived from Engelbreth-Holm-Swarm murine tumour). Morphogenesis of these unique three-dimensional structures was initiated by cell-directed remodelling of the exogenous matrix leading to reorganization of cells into matrixensheathed aggregates by 24 h after plating. The aggregates subsequently cavitated, so that by day 6 the cells were organized into hollow spheres in which apical cell surfaces faced lumina sealed by tight junctions and basal surfaces were surrounded by a distinct basal lamina. The profiles of proteins secreted into the apical (luminal) and basal (medium) compartments indicated that these alveoli-like structures were capable of an appreciable amount of vectorial secretion. Immunoprecipitation with a broad spectrum milk antiserum showed that more than 80% of caseins were secreted into the lumina, whereas iron-binding proteins (both lactoferrin and transferrin) were present in comparable amounts in each compartment. Thus, these mammary cells established protein targeting pathways directing milk-specific proteins to the luminal compartment. A time course monitoring secretory activity demonstrated that establishment of tissue-specific vectorial secretion and increased total and milk protein secretion coincided with functional alveolar

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. Rapid elevation of sodium transport through insulin is mediated by AKT in alveolar cells

    OpenAIRE

    Mattes, Charlott; Laube, Mandy; Thome, Ulrich H.

    2014-01-01

    Abstract Alveolar fluid clearance is driven by vectorial Na+ transport and promotes postnatal lung adaptation. The effect of insulin on alveolar epithelial Na+ transport was studied in isolated alveolar cells from 18–19‐day gestational age rat fetuses. Equivalent short‐circuit currents (I SC) were measured in Ussing chambers and different kinase inhibitors were used to determine the pathway of insulin stimulation. In Western Blot measurements the activation of mediators stimulated by insulin ...

  13. Rapid elevation of sodium transport through insulin is mediated by AKT in alveolar cells

    OpenAIRE

    Mattes, Charlott; Thome, Ulrich H.

    2014-01-01

    Alveolar fluid clearance is driven by vectorial Na+ transport and promotes postnatal lung adaptation. The effect of insulin on alveolar epithelial Na+ transport was studied in isolated alveolar cells from 18–19-day gestational age rat fetuses. Equivalent short-circuit currents (ISC) were measured in Ussing chambers and different kinase inhibitors were used to determine the pathway of insulin stimulation. In Western Blot measurements the activation of mediators stimulated by ...

  14. Alterations in the alveolar epithelium after injury leading to pulmonary fibrosis

    OpenAIRE

    Kasper, M; Haroske, G.

    1996-01-01

    This review discusses current knowledge of the involvement of the alveolar epithelium in tissue remodelling during fibrogenesis. The purpose of the present paper is to give an overview, including the authors' own results, of knowledge of ultrastructural alterations, proliferation kinetics and phenotypic changes of pneumocytes in experimental and clinical pathology of pulmonary fibrosis. After lung injury, the alveolar epithelial cells show ultrastructural alter...

  15. Jamming dynamics of stretch-induced surfactant release by alveolar type II cells

    OpenAIRE

    Majumdar, Arnab; Arold, Stephen P.; Bartolák-Suki, Erzsébet; Parameswaran, Harikrishnan; Suki, Béla

    2011-01-01

    Secretion of pulmonary surfactant by alveolar epithelial type II cells is vital for the reduction of interfacial surface tension, thus preventing lung collapse. To study secretion dynamics, rat alveolar epithelial type II cells were cultured on elastic membranes and cyclically stretched. The amounts of phosphatidylcholine, the primary lipid component of surfactant, inside and outside the cells, were measured using radiolabeled choline. During and immediately after stretch, cells secreted less...

  16. Generation of ESC-derived Mouse Airway Epithelial Cells Using Decellularized Lung Scaffolds.

    Science.gov (United States)

    Shojaie, Sharareh; Lee, Joyce; Wang, Jinxia; Ackerley, Cameron; Post, Martin

    2016-01-01

    Lung lineage differentiation requires integration of complex environmental cues that include growth factor signaling, cell-cell interactions and cell-matrix interactions. Due to this complexity, recapitulation of lung development in vitro to promote differentiation of stem cells to lung epithelial cells has been challenging. In this protocol, decellularized lung scaffolds are used to mimic the 3-dimensional environment of the lung and generate stem cell-derived airway epithelial cells. Mouse embryonic stem cell are first differentiated to the endoderm lineage using an embryoid body (EB) culture method with activin A. Endoderm cells are then seeded onto decellularized scaffolds and cultured at air-liquid interface for up to 21 days. This technique promotes differentiation of seeded cells to functional airway epithelial cells (ciliated cells, club cells, and basal cells) without additional growth factor supplementation. This culture setup is defined, serum-free, inexpensive, and reproducible. Although there is limited contamination from non-lung endoderm lineages in culture, this protocol only generates airway epithelial populations and does not give rise to alveolar epithelial cells. Airway epithelia generated with this protocol can be used to study cell-matrix interactions during lung organogenesis and for disease modeling or drug-discovery platforms of airway-related pathologies such as cystic fibrosis. PMID:27214388

  17. Alveolar Surfactant Homeostasis and the Pathogenesis of Pulmonary Disease

    OpenAIRE

    Whitsett, Jeffrey A.; Wert, Susan E.; Weaver, Timothy E.

    2010-01-01

    The alveolar region of the lung creates an extensive epithelial surface that mediates the transfer of oxygen and carbon dioxide required for respiration after birth. Maintenance of pulmonary function depends on the function of type II epithelial cells that synthesize and secrete pulmonary surfactant lipids and proteins, reducing the collapsing forces created at the air-liquid interface in the alveoli. Genetic and acquired disorders associated with the surfactant system cause both acute and ch...

  18. 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.

  19. 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...

  20. Basal Cell Carcinoma (BCC)

    Science.gov (United States)

    ... epithelioma, is the most common form of skin cancer. Basal cell carcinoma usually occurs on sun-damaged skin, especially ... other health issues. Infiltrating or morpheaform basal cell carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive ...

  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. Phorbol ester stimulates ethanolamine release from the metastatic basal prostate cancer cell line PC3 but not from prostate epithelial cell lines LNCaP and P4E6

    OpenAIRE

    Schmitt, J; Noble, A.; Otsuka, M; Berry, P.; Maitland, N J; Rumsby, M.G.

    2014-01-01

    Background: Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethanolamine (Etn) metabolites released to the medium. Methods: Prostate epithelial cell lines P4E6, LNCaP and PC3 were models of prostate cancer (PCa). PNT2C2 and PNT1A were models ...

  3. Pulmonary alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    B. Crestani

    2011-06-01

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

  4. 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.

  5. Asymmetric [14C]albumin transport across bullfrog alveolar epithelium

    International Nuclear Information System (INIS)

    Bullfrog lungs were prepared as planar sheets and bathed with Ringer solution in Ussing chambers. In the presence of a constant electrical gradient (20, 0, or -20 mV) across the tissue, 14C-labeled bovine serum albumin or inulin was instilled into the upstream reservoir and the rate of appearance of the tracer in the downstream reservoir was monitored. Two lungs from the same animal were used to determine any directional difference in tracer fluxes. An apparent permeability coefficient was estimated from a relationship between normalized downstream radioactivities and time. Results showed that the apparent permeability of albumin in the alveolar to pleural direction across the alveolar epithelial barrier is 2.3 X 10(-7) cm/s, significantly greater (P less than 0.0005) than that in the pleural to alveolar direction (5.3 X 10(-8) cm/s) when the tissue was short circuited. Permeability of inulin, on the other hand, did not show any directional dependence and averaged 3.1 X 10(-8) cm/s in both directions. There was no effect on radiotracer fluxes permeabilities of different electrical gradients across the tissue. Gel electrophoretograms and corresponding radiochromatograms suggest that the large and asymmetric isotope fluxes are not primarily due to digestion or degradation of labeled molecules. Inulin appears to traverse the alveolar epithelial barrier by simple diffusion through hydrated paracellular pathways. On the other hand, [14C]albumin crosses the alveolar epithelium more rapidly than would be expected by simple diffusion. These asymmetric and large tracer fluxes suggest that a specialized mechanism is present in alveolar epithelium that may be capable of helping to remove albumin from the alveolar space

  6. An estimation of mechanical stress on alveolar walls during repetitive alveolar reopening and closure.

    Science.gov (United States)

    Chen, Zheng-Long; Song, Yuan-Lin; Hu, Zhao-Yan; Zhang, Su; Chen, Ya-Zhu

    2015-08-01

    Alveolar overdistension and mechanical stresses generated by repetitive opening and closing of small airways and alveoli have been widely recognized as two primary mechanistic factors that may contribute to the development of ventilator-induced lung injury. A long-duration exposure of alveolar epithelial cells to even small, shear stresses could lead to the changes in cytoskeleton and the production of inflammatory mediators. In this paper, we have made an attempt to estimate in situ the magnitudes of mechanical stresses exerted on the alveolar walls during repetitive alveolar reopening by using a tape-peeling model of McEwan and Taylor (35). To this end, we first speculate the possible ranges of capillary number (Ca) ≡ μU/γ (a dimensionless combination of surface tension γ, fluid viscosity μ, and alveolar opening velocity U) during in vivo alveolar opening. Subsequent calculations show that increasing respiratory rate or inflation rate serves to increase the values of mechanical stresses. For a normal lung, the predicted maximum shear stresses are surface tension or viscosity, the maximum shear stress will notably increase, even at a slow respiratory rate. Similarly, the increased pressure gradients in the case of elevated surface or viscosity may lead to a pressure drop >300 dyn/cm(2) across a cell, possibly inducing epithelial hydraulic cracks. In addition, we have conceived of a geometrical model of alveolar opening to make a prediction of the positive end-expiratory pressure (PEEP) required to splint open a collapsed alveolus, which as shown by our results, covers a wide range of pressures, from several centimeters to dozens of centimeters of water, strongly depending on the underlying pulmonary conditions. The establishment of adequate regional ventilation-to-perfusion ratios may prevent recruited alveoli from reabsorption atelectasis and accordingly, reduce the required levels of PEEP. The present study and several recent animal experiments likewise

  7. Alveolar damage in AIDS-related Pneumocystis carinii pneumonia

    DEFF Research Database (Denmark)

    Benfield, T L; Prentø, P; Junge, Jette;

    1997-01-01

    P carinii pneumonia, whereas none without P carinii pneumonia had this finding (p < 0.05). Erosion of the type II pneumocyte was not observed. CONCLUSION: Inflammation, interstitial fibrosis, and alveolar epithelial erosion are characteristic features of P carinii pneumonia. The changes may form the......, exudate, fibrosts, type II pneumocyte proliferation, and cellular infiltration of the alveolar wall when compared with other lung diseases (all p < 0.05). Electron microscopy showed apposition of the trophozoite to the type I pneumocyte. Erosion of type I pneumocytes was observed in 13 of 15 patients with...

  8. Roles of neuropeptide substance P in transdifferentiation of premature rat type Ⅱ alveolar epithelial cells induced by hyperxia%神经肽P物质促进高氧诱导的胎鼠肺泡Ⅱ型上皮细胞转分化

    Institute of Scientific and Technical Information of China (English)

    黄波; 付红敏; 杨鸣; 方芳; 匡凤梧; 许峰

    2009-01-01

    目的 探讨感觉神经肽P物质(substance P,SP)对高氧诱导的胎鼠Ⅱ型肺泡上皮细胞(type Ⅱ alveolar epithelial cells,AECⅡ)转分化的影响.方法 剖官取出孕21 d(足月为22 d)SD胎鼠,分离纯化原代培养AECⅡ,采用随机分组法分为:空气暴露组(氧体积分数为0.21)、高氧暴露组(氧体积分数为0.95)、SP干预组,SP干预组于暴露前加入SP 1×10-6 mol/L,在置于氧体积分数为0.21和0.95中分别暴露12、24、和48 h,电镜观察AECⅡ的形态变化;免疫细胞化学染色法和流式细胞仪检测AECⅡ特异性肺泡表而活性蛋白-C(surfactant protein C,sp-C)及Ⅰ型肺泡上皮细胞(type Ⅰ alveolar epithelial cells,AEC Ⅰ)特异性水通道蛋5(aquaporin5,AQP5)的表达.结果 与空气组比较,高氧暴露后,AECⅡ SP-C的表达、SP-C细胞的表达率及荧光指数(fluorescence index,FI)明显降低,AQP5表达明显增加;而SP干预后,SP-C、AQP5表达都明显增加,形态学的损伤也有明显的改善.结论 SP可促进高氧诱导的胎鼠AECⅡ的转分化,在肺损伤修复中可能起重要作用.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 石棉暴露下内质网应激在肺泡上皮细胞凋亡中的作用机制%THE MECHANISM OF ENDOPLASMIC RETICULUM STRESS INDUCING ALVEOLAR EPI-THELIAL CELLS APOPTOSIS UNDERLYING ASBESTOS EXPOSURE

    Institute of Scientific and Technical Information of China (English)

    周煦; 刘刚

    2014-01-01

    Objective To investigate the role of endoplasmic reticulum stress ( ERS) in asbestos-induced Alveolar epithelial cell apoptosis.Methods A549 cells were treated with asbestos to observe the expression of ERS proteins and apop-tosis gene by immunofluorescence staining and western blotting.Results Under asbestos exposure, the expression of Bip, GRP94, IRE-1α, BAX and BAK are up-regulated.There is a positive correlativity of the expression of proteins to the ex-posure time of asbestos.Conclusion Endoplasmic reticulum stress takes part in asbestos-induced apoptosis.%目的:探讨石棉暴露下内质网应激在细胞凋亡中的作用机制。方法应用石棉处理A549细胞,免疫荧光染色免疫法和免疫印迹法观察内质网应激( ERS)相关蛋白与促凋亡基因的变化。结果石棉暴露下,ERS相关蛋白Bip、IRE-1α和GRP94,以及促凋亡基因BAX、BAK蛋白表达均上调,且与石棉暴露时间呈正相关。结论内质网应激参与了石棉诱导的细胞凋亡。

  14. Atomic force microscope elastography reveals phenotypic differences in alveolar cell stiffness

    OpenAIRE

    Azeloglu, Evren U.; Bhattacharya, Jahar; COSTA, KEVIN D.

    2008-01-01

    To understand the connection between alveolar mechanics and key biochemical events such as surfactant secretion, one first needs to characterize the underlying mechanical properties of the lung parenchyma and its cellular constituents. In this study, the mechanics of three major cell types from the neonatal rat lung were studied; primary alveolar type I (AT1) and type II (AT2) epithelial cells and lung fibroblasts were isolated using enzymatic digestion. Atomic force microscopy indentation wa...

  15. Increased alveolar soluble annexin V promotes lung inflammation and fibrosis.

    Science.gov (United States)

    Buckley, Susan; Shi, Wei; Xu, Wei; Frey, Mark R; Moats, Rex; Pardo, Annie; Selman, Moises; Warburton, David

    2015-11-01

    The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesised that alveolar soluble annexin V contributes to lung fibrosis, based on the observation that human IPF bronchoalveolar lavage fluid (BALF) containing high annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when annexin V was depleted from the BALF. Conditioned medium from annexin V-treated alveolar epithelial type 2 cells (AEC2), but not annexin V per se, induced proliferation of human fibroblasts and contained pro-fibrotic, IPF-associated proteins, as well as pro-inflammatory cytokines that were found to correlate tightly (r>0.95) with annexin V levels in human BALF. ErbB2 receptor tyrosine kinase in AECs was activated by annexin V, and blockade reduced the fibrotic potential of annexin V-treated AEC-conditioned medium. In vivo, aerosol delivery of annexin V to mouse lung induced inflammation, fibrosis and increased hydroxyproline, with activation of Wnt, transforming growth factor-β, mitogen-activated protein kinase and nuclear factor-κB signalling pathways, as seen in IPF. Chronically increased alveolar annexin V levels, as reflected in increased IPF BALF levels, may contribute to the progression of IPF by inducing the release of pro-fibrotic mediators. PMID:26160872

  16. Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model.

    Science.gov (United States)

    Douville, Nicholas J; Zamankhan, Parsa; Tung, Yi-Chung; Li, Ran; Vaughan, Benjamin L; Tai, Cheng-Feng; White, Joshua; Christensen, Paul J; Grotberg, James B; Takayama, Shuichi

    2011-02-21

    Studies using this micro-system demonstrated significant morphological differences between alveolar epithelial cells (transformed human alveolar epithelial cell line, A549 and primary murine alveolar epithelial cells, AECs) exposed to combination of solid mechanical and surface-tension stresses (cyclic propagation of air-liquid interface and wall stretch) compared to cell populations exposed solely to cyclic stretch. We have also measured significant differences in both cell death and cell detachment rates in cell monolayers experiencing combination of stresses. This research describes new tools for studying the combined effects of fluid mechanical and solid mechanical stress on alveolar cells. It also highlights the role that surface tension forces may play in the development of clinical pathology, especially under conditions of surfactant dysfunction. The results support the need for further research and improved understanding on techniques to reduce and eliminate fluid stresses in clinical settings. PMID:21152526

  17. Alveolar Ridge Augmentation with Titanium Mesh. A Retrospective Clinical Study

    OpenAIRE

    Poli, Pier P; Beretta, Mario; Cicciù, Marco; Maiorana, Carlo

    2014-01-01

    An adequate amount of bone all around the implant surface is essential in order to obtain long-term success of implant restoration. Several techniques have been described to augment alveolar bone volume in critical clinical situations, including guided bone regeneration, based on the use of barrier membranes to prevent ingrowth of the epithelial and gingival connective tissue cells. To achieve this goal, the use of barriers made of titanium micromesh has been advocated. A total of 13 patients...

  18. Development of an in vitro model of human bronchial epithelial barrier to study nanoparticle translocation.

    Science.gov (United States)

    George, Isabelle; Vranic, Sandra; Boland, Sonja; Courtois, Arnaud; Baeza-Squiban, Armelle

    2015-02-01

    Inhalation is the most frequent route of unintentional exposure to nanoparticles (NPs). Our aim was to compare different in vitro models of human lung epithelial monolayers for their suitability to assess the translocation of 50 nm fluorescently labelled silica NPs (50 nm-SiO(2)-FITC-NPs). Human bronchial epithelial cell lines NCI-H292 and Calu-3 as well as human alveolar cell line A549 were seeded onto Transwell filters (TF) separating the well into an apical and a basal compartment. Measurements of the transepithelial electric resistance and monitoring the paracellular transport of a fluorescent marker (Lucifer Yellow) have shown that only Calu-3 cells formed a tight epithelium. In the absence of cells 4% of the initially applied NP concentration was found to cross the TF but the majority remained trapped inside the filter. After 24 h of treatment, 50 nm-SiO(2)-FITC-NPs were taken up by all cell types but their translocation was inversely correlated to the efficiency to prevent LY passage: translocation represented 3% of the initially apically applied NP concentration for Calu-3 cells, 9% for NCI-H292 cells and 35% for A549 cells. In conclusion, 50 nm-SiO(2)-FITC-NPs can cross different bronchial epithelial barriers, but the Calu-3 cell line appears to be the most relevant model for studying NP translocation. PMID:25197033

  19. 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

  20. 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.

  1. New insights of P2X7 receptor signaling pathway in alveolar functions

    OpenAIRE

    Mishra, Amarjit

    2013-01-01

    Purinergic P2X7 receptor (P2X7R), an ATP-gated cation channel, is unique among all other family members because of its ability to respond to various stimuli and to modulate pro-inflammatory signaling. The activation of P2X7R in immune cells is absolutely required for mature interleukin -1beta (IL-1beta) and IL-18 production and release. Lung alveoli are lined by the structural alveolar epithelial type I (AEC I) and alveolar epithelial type II cells (AEC II). AEC I plays important roles in alv...

  2. 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...

  3. Nevoid Basal Cell Carcinoma Syndrome

    Science.gov (United States)

    ... Nevoid Basal Cell Carcinoma Syndrome Request Permissions Nevoid Basal Cell Carcinoma Syndrome Approved by the Cancer.Net Editorial Board , 04/2016 What is Nevoid Basal Cell Carcinoma Syndrome? Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is ...

  4. The role of P63 postive basal cell in re-epithelialization of prostatic urethra after resection of prostate%P63阳性基底细胞在前列腺切除术后尿道再上皮化中的作用

    Institute of Scientific and Technical Information of China (English)

    刘旋; 孙兆林

    2015-01-01

    Objective:To evaluate the role of P63 postive basal cell in re-epithelialization of prostatic urethra after resection of the prostate) . Methods:15 older male dogs were treated with resection of the prostate. Specimens of the residual wounds were taken at days 3, 7 and 14 postoperatively to evaluate the expression level of P63 and with HE and immunohistochemical staining. Results:P63 positive cells were detected occasionally in the wounds three days after surgery. At days 7, P63 postive cells appeared lamellar distri-bution connecting with remaining prostatic tissue and at days 14, P63 positive expression was observed in basal cells of newborn urothe-lium. Coclusion:The remaining prostatic tissue plays a great role in re-epithelialization of prostatic urethra after TmLRP and P63 pos-tive cells of basal lamina may be one of the origins of cells for the process.%目的::探讨前列腺切除术后P63阳性基底细胞在前列腺部尿道上皮修复过程中的作用。方法:15只老年家犬行前列腺增生切除术,术后第3、7、14天取材行HE染色和免疫组织化学染色分别观察前列腺部尿道上皮修复过程和P63蛋白表达水平。结果:术后3 d手术创面偶见P63阳性细胞;术后7 d可见片状P63阳性细胞,且这些细胞与残余前列腺组织相连续;术后14 d可见新生尿道上皮基底层细胞阳性表达P63。结论:残余前列腺组织是BPH术后尿道再上皮化的重要组织,而位于基底层的P63阳性细胞可能是这一修复过程的源细胞之一。

  5. 油烟中细颗粒物致胎鼠肺泡Ⅱ型上皮细胞DNA损伤的研究%Assessment of DNA Damage Induced by Cooking Oil Fumes Particulate in the Mice Alveolar Type Ⅱ Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    梁春梅; 操基玉; 王勇; 冯哲伟; 汪磊

    2011-01-01

    目的 探讨油烟中的细颗粒物(PM2.5)对原代培养的胎鼠肺泡Ⅱ型上皮细胞(AECⅡ)DNA的损伤效应.方法 将1只妊娠18d的SPF级ICR小鼠体内的胎鼠肺组织制成AECⅡ细胞悬液,取对数生长期细胞,调整细胞密度为1×106/ml,分别加入终浓度为0(溶剂对照,含10% FBS的DMEM)、12.5、25、50、100μg/ml的PM2.5(来源于烹调油烟)溶液,培养6、12h后进行MTT试验和彗星试验,并检测AECⅡ细胞的尾长、尾部DNA百分比、尾矩和Olive尾矩.结果与溶剂对照组比较,50、100 μg/ml PM2.5染毒6、12 h时胎鼠AECⅡ存活率下降,差异均有统计学意义(P<0.05);12.5、25、50μg/mlPM2.5染毒6、12h时胎鼠AECⅡ的尾长、尾部DNA百分比、尾矩和Olive尾矩升高,差异均有统计学意义(P<0.05).随着PM2.5染毒浓度的升高,AECⅡ细胞存活率呈下降趋势,尾长、尾部DNA百分比、尾矩和Olive尾矩均呈上升趋势.结论油烟中的PM2.5可降低AECⅡ的细胞活性,对AECⅡ的DNA具有损伤效应.%Objective To investigate DNA damage induced by cooking oil fume participate (PM2.5) in the mice alveolar type II epithelial cells in primary cultured. Methods The mice alveolar type Ⅱ epithelial cells were isolated from 18 days old fetuses of ICR mice. The cells in exponential phase were cultured at a density of 1×106 cells/ml,AEC II cells were treated with PM2.5 at the doses of 0 μg/ml (the solvent control, 10% FBS of DMEM), 12.5,25,50 and 100 μg/ml for 6 and 12 h. AEC Ⅱ cell proliferation were detected with MTT assays and the comet assay was used to detect the Olive tail moment,tail moment,tail length and tail intensity. Results The survival rate of AEC II was decreased with a dose-dependent manner; Olive tail moment, tail moment, tail length and tail intensity were increased with a dose-dependent manner. Conclusion Cooking oil fume participate may decrease the viability of AEC II cells and produce evident DNA damage.

  6. Protective effects of amygdalin on hyperoxia-exposed type Ⅱ alveolar epithelial cells isolated from premature rat lungs in vitro%苦杏仁甙对高氧暴露早产鼠肺泡Ⅱ型细胞的保护作用

    Institute of Scientific and Technical Information of China (English)

    常立文; 祝华平; 李文斌; 刘汉楚; 张谦慎; 陈红兵

    2005-01-01

    目的探讨苦杏仁甙对体外高氧暴露早产鼠肺泡Ⅱ型细胞( type 2 alveolar epithelial cell,AECⅡ)的保护作用机制.方法原代培养早产鼠AECⅡ,建立高氧细胞模型,采用MTT比色法、流式细胞术、免疫印迹(Western blot)、逆转录聚合酶链反应(RT-PCR)等方法,观察苦杏仁甙对高氧暴露早产鼠AECⅡ增殖及表面活性物质蛋白(surfactant associated protein, SP)mRNA表达的影响.结果高氧暴露导致早产鼠AECⅡ增殖抑制,AECⅡSPs mRNA表达降低.MTT试验显示,苦杏仁甙50~200μmol/L时呈剂量依赖方式促进早产鼠AECⅡ细胞增殖,200 μmol/L浓度时,其作用最强,400 μmol/L浓度时反而呈抑制作用.200 μmol/L苦杏仁甙可显著促进体外高氧暴露AECⅡ增殖,提高其SP mRNA表达水平.结论高氧暴露导致早产鼠AECⅡ增殖抑制及SP mRNA表达降低,200 μmol/L苦杏仁甙对体外高氧暴露的早产鼠AECⅡ有一定保护作用.

  7. CT in alveolar proteinosis

    International Nuclear Information System (INIS)

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

  8. Effects of simvastatin on the transdifferentiation of hypoxia and reoxygenation injury of alveolar epithelial type Ⅱ cells%辛伐他汀促进缺氧复氧损伤后肺泡Ⅱ型上皮细胞转分化的研究

    Institute of Scientific and Technical Information of China (English)

    武雅琴; 冯冬杰; 蒋峰; 张治; 黄建峰; 张帅; 尹荣; 许林

    2012-01-01

    目的 观察辛伐他汀是否能在体外促进缺氧复氧损伤后肺泡Ⅱ型上皮细胞向Ⅰ型细胞转分化,并探讨其作用机制.方法 体外培养小鼠肺泡上皮细胞MLE-12,建立缺氧复氧损伤模型,分为空白对照组(Blank)、辛伐他汀组(Sim)及缺氧复氧组(H/R),分别于缺氧2h后复氧0h、1d、3d和7d共4个时间点获取细胞,流式细胞仪检测肺泡Ⅰ型/Ⅱ型细胞表面特异性标志Caveolin- 1/Pro-SP-C 阳性细胞数百分比,Western blot法测定各组Pro-SP-C和Caveolin-1蛋白水平,最后行甲羟戊酸通路竞争实验观察左旋甲羟戊酸( L-meva)对辛伐他汀作用的影响.结果 流式细胞术结果显示:在缺氧复氧早期(d0及d1),Sim组较H/R组Caveolin-1/Pro-SP-C百分比显著降低;至d3和d7百分比则显著升高;Western blot结果显示:与H/R组比较,Sim组Pro-SP-C蛋白水平在d0及d1最高,至d3和d7则显著下降,Caveolin-1蛋白水平在d1最低,至d3和d7则逐渐升高,两者比较均有显著统计学差异(P<0.01).L-meva竞争试验显示:与Sim组比较,Sim+ L-meva组在各个时间点Pro-SP-C和Caveolin-1蛋白水平差异无统计学意义(P>0.05).结论 辛伐他汀可以促进缺氧复氧损伤后肺泡Ⅱ型上皮细胞向Ⅰ型细胞的转分化,但其作用机制不依赖于甲羟戊酸通路.%Objective To investigate the role of simvastatin in the transdifferentiation of hypoxia and reoxygenation injury of type Ⅱ alveolar epithelial cells and explore the underlying mechanisms.Methods Mouse AT Ⅱ cell line MLE-12 were subjected to hypoxia reoxygenation (H/R) injury.Blank,control and simvastatin-treated groups (20 μmol/L) were designed in the present study.The percentage of Caveolin-1/Pro-SP-C expression in the different points was assessed by flow cytometry double-staining.The protein levels of pro-surfactant protein-C (Pro-SP-C) and Caveolin-1 in AT Ⅱ cells was determined by Western blotting.And the protein levels of Pro-SP-C and Caveolin-1 was

  9. Hemorragia alveolar associada a nefrite lúpica Alveolar hemorrhage associated with lupus nephritis

    Directory of Open Access Journals (Sweden)

    Ricardo Henrique de Oliveira Braga Teixeira

    2003-12-01

    Full Text Available Hemorragia alveolar, como causa de insuficiência respiratória, é pouco freqüente, com diversas etiologias possíveis. Entre elas, o lúpus eritematoso sistêmico, que se apresenta geralmente como síndrome pulmão-rim, possui alta morbimortalidade. Acredita-se que a patogênese da microangiopatia, tanto renal como pulmonar, esteja associada ao depósito de imunocomplexos, que ativariam as vias de apoptose celular. Relatam-se dois casos de pacientes com nefrite lúpica que evoluíram com hemorragia alveolar associada à insuficiência respiratória necessitando de ventilação mecânica com evoluções totalmente distintas frente às terapias farmacológicas. O achado de anticorpos antimembrana basal em um dos casos evidencia a multiplicidade de mecanismos fisiopatológicos possivelmente envolvidos, que poderiam justificar as respostas heterogêneas frente aos tratamentos disponíveis.Alveolar hemorrhage leading to respiratory failure is uncommon. Various etiologies have been reported, including systemic lupus erythematosus, which generally presents as pulmonary-renal syndrome. It is believed that the pathogenesis of microangiopathy is related to deposits of immune complexes that lead to activation of cellular apoptosis. The authors report two cases of alveolar hemorrhage and respiratory failure, both requiring mechanical ventilation. The two cases had opposite outcomes after pharmacological therapy. The presence of anti-glomerular basement membrane antibodies in one of the cases demonstrates the multiplicity of physiopathological mechanisms that may be involved. This multiplicity of mechanisms provides a possible explanation for the heterogeneous responses to the available treatments.

  10. Genetics Home Reference: pulmonary alveolar microlithiasis

    Science.gov (United States)

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

  11. Altered lung morphogenesis, epithelial cell differentiation and mechanics in mice deficient in the Wnt/β-catenin antagonist Chibby.

    Directory of Open Access Journals (Sweden)

    Damon Love

    Full Text Available The canonical Wnt/β-catenin pathway plays crucial roles in various aspects of lung morphogenesis and regeneration/repair. Here, we examined the lung phenotype and function in mice lacking the Wnt/β-catenin antagonist Chibby (Cby. In support of its inhibitory role in canonical Wnt signaling, expression of β-catenin target genes is elevated in the Cby(-/- lung. Notably, Cby protein is prominently associated with the centrosome/basal body microtubule structures in embryonic lung epithelial progenitor cells, and later enriches as discrete foci at the base of motile cilia in airway ciliated cells. At birth, Cby(-/- lungs are grossly normal but spontaneously develop alveolar airspace enlargement with reduced proliferation and abnormal differentiation of lung epithelial cells, resulting in altered pulmonary function. Consistent with the Cby expression pattern, airway ciliated cells exhibit a marked paucity of motile cilia with apparent failure of basal body docking. Moreover, we demonstrate that Cby is a direct downstream target for the master ciliogenesis transcription factor Foxj1. Collectively, our results demonstrate that Cby facilitates proper postnatal lung development and function.

  12. Epithelial fibroblast triggering and interactions in pulmonary fibrosis

    OpenAIRE

    Noble, P W

    2008-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterised by repeated injury to the alveolar epithelium with loss of lung epithelial cells and abnormal tissue repair, resulting in excessive accumulation of fibroblasts and myofibroblasts, deposition of extracellular matrix components and distortion of lung architecture, eventually leading to respiratory failure. There is growing circumstantial evidence to suggest that in IPF the alveolar epithelium is prone to undergoing programmed cell death follo...

  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. Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Eekelen, S.J.M.

    2015-01-01

    A basal reinforced piled embankment consists of a reinforced embankment on a pile foundation. The reinforcement consists of one or more horizontal layers of geosynthetic reinforcement (GR) installed at the base of the embankment. The design of the GR is the subject of this thesis. A basal reinforce

  15. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    International Nuclear Information System (INIS)

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGFβ1-mediated lytic phase. EBV lytic reactivation by TGFβ1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM181552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  16. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Malizia, Andrea P.; Lacey, Noreen [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland); Walls, Dermot [School of Biotechnology, Dublin City University. Dublin, 9. Ireland (Ireland); Egan, Jim J. [Advanced Lung Disease and Lung Transplant Program, Mater Misericordiae University Hospital. 44, Eccles Street. Dublin, 7. Ireland (Ireland); Doran, Peter P., E-mail: peter.doran@ucd.ie [Clinical Research Centre, School of Medicine and Medical Science, University College Dublin. 21, Nelson Street. Dublin, 7. Ireland (Ireland)

    2009-07-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  17. Autoimmune basal ganglia disorders.

    Science.gov (United States)

    Dale, Russell C; Brilot, Fabienne

    2012-11-01

    The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. PMID:22832771

  18. 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.

  19. 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

  20. Application of linear integration in the morphometric study of mild and severe pulmonary alveolar injury.

    Science.gov (United States)

    Coulombe, P A; Côté, M G

    1988-02-01

    In this study we applied linear integration morphometry to characterize the pulmonary alveolar reaction to toxic injury and to study possible relationships between the major tissue and cell compartments of alveolar tissue, normal and injured. Acute alveolar injury of mild and severe intensity was induced in Swiss-Webster mice by the ip administration of the chemicals diquat (4 mg/kg) and butylated hydroxytoluene (BHT; 400 mg/kg). Animals were sacrificed at Days 1 and 2 after diquat treatment and at Days 1, 3, and 5 after BHT treatment. Sampling and analysis of alveolar tissue were conducted at both levels of light and electron microscopy. Thickness distributions of arithmetic and reciprocal intercepts, as well as the arithmetic (tau) and harmonic (tau h) mean thicknesses, were established for the following alveolar compartments: septum, alveolo-capillary barrier (ACB), type I and total epithelia, capillary endothelium, and interstitium. A relative measure of the pulmonary diffusion capacity and the capillary load of alveolar septa were also determined. The parameters calculated from these thickness distributions, such as their slopes, percentages of thin intercepts, and tau/tau h ratios, proved very sensitive and useful in the detection and characterization of morphological alterations in the type I epithelial and capillary endothelial cells following either mild or severe alveolar injury. The epithelial, endothelial, and interstitial layers of pulmonary septa were all characterized by their own pattern of structural changes, so that it proved impossible to relate them in a simple way to the tissue reaction, which can be easily studied at the light microscopic level. Linear integration morphometry thus proved very useful as a morphometric approach to the study of pulmonary alveolar injury and repair. PMID:3335253

  1. 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.

  2. 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

  3. Claudins: Gatekeepers of lung epithelial function.

    Science.gov (United States)

    Schlingmann, Barbara; Molina, Samuel A; Koval, Michael

    2015-06-01

    The lung must maintain a proper barrier between airspaces and fluid filled tissues in order to maintain lung fluid balance. Central to maintaining lung fluid balance are epithelial cells which create a barrier to water and solutes. The barrier function of these cells is mainly provided by tight junction proteins known as claudins. Epithelial barrier function varies depending on the different needs within the segments of the respiratory tree. In the lower airways, fluid is required to maintain mucociliary clearance, whereas in the terminal alveolar airspaces a thin layer of surfactant enriched fluid lowers surface tension to prevent airspace collapse and is critical for gas exchange. As the epithelial cells within the segments of the respiratory tree differ, the composition of claudins found in these epithelial cells is also different. Among these differences is claudin-18 which is uniquely expressed by the alveolar epithelial cells. Other claudins, notably claudin-4 and claudin-7, are more ubiquitously expressed throughout the respiratory epithelium. Claudin-5 is expressed by both pulmonary epithelial and endothelial cells. Based on in vitro and in vivo model systems and histologic analysis of lungs from human patients, roles for specific claudins in maintaining barrier function and protecting the lung from the effects of acute injury and disease are being identified. One surprising finding is that claudin-18 and claudin-4 control lung cell phenotype and inflammation beyond simply maintaining a selective paracellular permeability barrier. This suggests claudins have more nuanced roles for the control of airway and alveolar physiology in the healthy and diseased lung. PMID:25951797

  4. 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...

  5. 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

  6. Functional ion channels in pulmonary alveolar type I cells support a role for type I cells in lung ion transport

    OpenAIRE

    Johnson, Meshell D.; Bao, Hui-Fang; Helms, My N.; Chen, Xi-Juan; Tigue, Zac; Jain, Lucky; Dobbs, Leland G.; Eaton, Douglas C.

    2006-01-01

    Efficient gas exchange in the lungs depends on regulation of the amount of fluid in the thin (average 0.2 μm) liquid layer lining the alveolar epithelium. Fluid fluxes are regulated by ion transport across the alveolar epithelium, which is composed of alveolar type I (TI) and type II (TII) cells. The accepted paradigm has been that TII cells, which cover 95% of the surface area, provide a route for water absorption. Here we present data that TI cells contain functional epithelial Na+ channels...

  7. New insights of P2X7 receptor signaling pathway in alveolar functions.

    Science.gov (United States)

    Mishra, Amarjit

    2013-01-01

    Purinergic P2X7 receptor (P2X7R), an ATP-gated cation channel, is unique among all other family members because of its ability to respond to various stimuli and to modulate pro-inflammatory signaling. The activation of P2X7R in immune cells is absolutely required for mature interleukin -1beta (IL-1beta) and IL-18 production and release. Lung alveoli are lined by the structural alveolar epithelial type I (AEC I) and alveolar epithelial type II cells (AEC II). AEC I plays important roles in alveolar barrier protection and fluid homeostasis whereas AEC II synthesizes and secrete surfactant and prevents alveoli from collapse. Earlier studies indicated that purinergic P2X7 receptors were specifically expressed in AEC I. However, their implication in alveolar functions has not been explored. This paper reviews two important signaling pathways of P2X7 receptors in surfactant homeostatsis and Acute Lung Injury (ALI). Thus, P2X7R resides at the critical nexus of alveolar pathophysiology. PMID:23634990

  8. Distinctive Patterns of CTNNB1 (β-Catenin) Alterations in Salivary Gland Basal Cell Adenoma and Basal Cell Adenocarcinoma.

    Science.gov (United States)

    Jo, Vickie Y; Sholl, Lynette M; Krane, Jeffrey F

    2016-08-01

    Salivary gland basaloid neoplasms are diagnostically challenging. Limited publications report that some basal cell adenomas harbor CTNNB1 mutations, and nuclear β-catenin expression is prevalent. We evaluated β-catenin expression in basal cell adenomas and adenocarcinomas in comparison with salivary tumors in the differential diagnosis and performed targeted genetic analysis on a subset of cases. β-catenin immunohistochemistry was performed on formalin-fixed, paraffin-embedded whole sections from 73 tumors. Nuclear staining was scored semiquantitatively by extent and intensity. DNA was extracted from 6 formalin-fixed, paraffin-embedded samples (5 basal cell adenomas, 1 basal cell adenocarcinoma) for next-generation sequencing. Nuclear β-catenin staining was present in 18/22 (82%) basal cell adenomas; most were diffuse and strong and predominant in the basal component. Two of 3 basal cell adenocarcinomas were positive (1 moderate focal; 1 moderate multifocal). All adenoid cystic carcinomas (0/20) and pleomorphic adenomas (0/20) were negative; 2/8 epithelial-myoepithelial carcinomas showed focal nuclear staining. Most β-catenin-negative tumors showed diffuse membranous staining in the absence of nuclear staining. Four of 5 basal cell adenomas had exon 3 CTNNB1 mutations, all c.104T>C (p.I35T). Basal cell adenocarcinoma showed a more complex genomic profile, with activating mutations in PIK3CA, biallelic inactivation of NFKBIA, focal CYLD deletion, and without CTNNB1 mutation despite focal β-catenin expression. Nuclear β-catenin expression has moderate sensitivity (82%) for basal cell adenoma but high specificity (96%) in comparison with its morphologic mimics. CTNNB1 mutation was confirmed in most basal cell adenomas tested, and findings in basal cell adenocarcinoma suggest possible tumorigenic mechanisms, including alterations in PI3K and NF-κB pathways and transcriptional regulation. PMID:27259009

  9. Phenotypes of the ovarian follicular basal lamina predict developmental competence of oocytes

    OpenAIRE

    Irving-Rodgers, Helen F.; Morris, Stephanie; Collett, Rachael A.; Peura, Teija T.; Davy, Margaret; Jeremy G. Thompson; Mason, Helen D; Rodgers, Raymond J.

    2008-01-01

    BACKGROUND The ovarian follicular basal lamina underlies the epithelial membrana granulosa and maintains the avascular intra-follicular compartment. Additional layers of basal lamina occur in a number of pathologies, including pili annulati and diabetes. We previously found additional layers of follicular basal lamina in a significant percentage of healthy bovine follicles. We wished to determine if this phenomenon existed in humans, and if it was related to oocyte function in the bovine. MET...

  10. 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...

  11. Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes.

    Science.gov (United States)

    Sallenave, J M; Shulmann, J; Crossley, J; Jordana, M; Gauldie, J

    1994-12-01

    The regulation of the activity of potentially harmful proteinases secreted by neutrophils during inflammation is important for the prevention of excessive tissue injury. Secretory leukocyte proteinase inhibitor (SLPI), also called antileukoprotease (ALP) or mucus proteinase inhibitor (MPI), is a serine proteinase inhibitor that has been found in a variety of mucous secretions and that is secreted by bronchial epithelial cells. We recently reported the presence of SLPI and of an elastase-specific inhibitor (ESI), also called elafin, in the supernatants of two cell lines, NCI-H322 and A549, which have features of Clara cells and type II alveolar cells, respectively. We showed in addition that epithelial cell lines produce the elastase-specific inhibitor as a 12 to 16 kD precursor of the elafin molecule (6 kD) called pre-elafin. In the present study, we show that NCI-H322 cells produced higher amounts of both inhibitors than A549 cells and that basal production of SLPI in both cell lines is higher than the production of elafin/pre-elafin. In addition, we show that interleukin-1 beta and tumor necrosis factor induce significant SLPI expression and are major inducers of elafin/pre-elafin expression. Moreover, induction is greater in A549 cells than in NCI-H322 cells. The implications of these findings for the peripheral airways are twofold: (1) alveolar epithelial cells may respond to cytokines secreted during the onset of inflammation by increasing their antiprotease shield; (2) elafin/pre-elafin seems to be a true local "acute phase reactant" whereas SLPI, in comparison, may be less responsive to local inflammatory mediators. PMID:7946401

  12. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  13. 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...

  14. Pulmonary alveolar microlithiasis with calcified pleural plaques

    OpenAIRE

    Malhotra Balbir; Sabharwal Raghu; Singh Mandeep; Singh Amarjeet

    2010-01-01

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

  15. 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.

  16. The effect of phospholipid transfer protein on cigarette smoke extract induced epithelial-mesenchymal transition of rat alveolar type Ⅱ cells%磷脂转运蛋白在烟草诱导RLE-6TN细胞株发生上皮间质转化中的作用

    Institute of Scientific and Technical Information of China (English)

    巫凤苹; 陈亚娟; 余秀英; 廖科; 李丹丹; 陈虹

    2016-01-01

    Objective To investigate the effect of phospholipid transfer protein(PLTP) on cigarette smoke extract(CSE) induced epithelial-mesenchymal transition(EMT) in rat alveolar Type Ⅱ cells (RLE-6TN).Methods CSE of different concentrations (0%,0.25%,0.5% and 1%) was co-cultured for 2 or 3days with RLE-6TN,either pre-treated or not pre-treated with siRNA-PLTP for 6 h.Expression levels of E-cadherin mRNA and Vimentin mRNA were examined by RT-PCR,while expression levels of PLTP,E-cadherin,N-cadherin and Vimentin were examined by Western blot.Results Our results showed that the expression of E-cadherin mRNA decreased in CSE-treated groups:1.01 ± 0.05,0.74 ± 0.05,0.65 ± 0.03,0.30 ±0.08 respectively at different concentrations of CSE (0 %,0.25%,0.5 %,and 1.0%);while the level of Vimentin mRNA increased significantly in 1% CSE treated cells (1.88 ± O.49),compared with control cells (1.01 ±0.20).Treatment with CSE at different concentrations (0%,0.25%,0.5% and 1%) showed that the protein levels of PLTP were 0.42 ± 0.02,0.89 ± 0.25,1.08 ± 0.18,1.61 ± 0.06 respectively;those of E-cadherin were 1.61 ± 0.04,1.08 ± 0.10,0.62 ± 0.08,0.68 ± 0.17,respectively;those of N-cadherin were 0.60 ± 0.14,0.57 ± 0.26,0.88 ± 0.30,1.94 ± 0.54,respectively;and those of Vimentin were 0.61 ± 0.05,0.98 ± 0.16,1.07 ± 0.14,1.34 ± 0.19,respectively;all P < 0.05 when the 1% CSE group was compared with the control group.EMT induced by CSE was significantly inhibited by siRNA-PLTP.Conclusion PLTP may be involved in CSE induced EMT of rat alveolar cells.%目的 探讨磷脂转运蛋白(PLTP)在烟草提取物(CSE)诱导大鼠Ⅱ型肺泡上皮细胞株RLE-6TN发生上皮间质转化(EMT)中的作用.方法 体外培养RLE-6TN细胞株24 h,分为4组,每组3孔,分别加入0%、0.25%、0.5%和1% CSE培养2d,检测E-钙黏蛋白和波形蛋白mRNA表达以及细胞和CSE共培养3d检测PLTP、EMT相关蛋白(E-钙黏蛋白、N-钙黏蛋白和波形

  17. 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.

  18. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    OpenAIRE

    Arwa Flemban; David Qualtrough

    2015-01-01

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in t...

  19. Kerbs von Lungren 6 antigen is a marker of alveolar inflammation but not of infection in patients with acute respiratory distress syndrome

    OpenAIRE

    Nathani, Nazim; Perkins, Gavin D; Tunnicliffe, William; Murphy, Nick; Manji, Mav; Thickett, David R.

    2008-01-01

    Background Kerbs von Lungren 6 antigen (KL-6) is expressed on the surface of alveolar type II cells, and elevated plasma and epithelial lining fluid levels of KL-6 have previously been shown to correlate with the severity of disease and survival in acute respiratory distress syndrome (ARDS). The relationship between alveolar inflammation and KL-6 measurements has not been ascertained. We hypothesized that the elevation of KL-6 in ARDS is dependent upon the severity of neutrophilic inflammatio...

  20. Regulation and repair of the alveolar-capillary barrier in acute lung injury.

    Science.gov (United States)

    Bhattacharya, Jahar; Matthay, Michael A

    2013-01-01

    Considerable progress has been made in understanding the basic mechanisms that regulate fluid and protein exchange across the endothelial and epithelial barriers of the lung under both normal and pathological conditions. Clinically relevant lung injury occurs most commonly from severe viral and bacterial infections, aspiration syndromes, and severe shock. The mechanisms of lung injury have been identified in both experimental and clinical studies. Recovery from lung injury requires the reestablishment of an intact endothelial barrier and a functional alveolar epithelial barrier capable of secreting surfactant and removing alveolar edema fluid. Repair mechanisms include the participation of endogenous progenitor cells in strategically located niches in the lung. Novel treatment strategies include the possibility of cell-based therapy that may reduce the severity of lung injury and enhance lung repair. PMID:23398155

  1. 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 ...

  2. Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis

    OpenAIRE

    Serrano-Mollar, Anna; Nácher, María; Gay-Jordi, Gemma; Closa, Daniel; Xaubet, Antoni; Bulbena, Oriol

    2007-01-01

    [Rationale]: Transplantation of stem cells has been proposed as a strategy for repair of lung fibrosis. Nevertheless, many studies have yielded controversial results that currently limit the potential use of these cells as an efficient treatment. Alveolar type II cells are the progenitor cells of the pulmonary epithelium and usually proliferate after epithelial cell injury. During lung fibrosis, however, the altered regeneration process leads to uncontrolled fibroblast proliferation. [Objecti...

  3. Variable stretch pattern enhances surfactant secretion in alveolar type II cells in culture

    OpenAIRE

    Arold, Stephen P.; Bartolák-Suki, Erzsébet; Suki, Béla

    2009-01-01

    Secretion of pulmonary surfactant that maintains low surface tension within the lung is primarily mediated by mechanical stretching of alveolar epithelial type II (AEII) cells. We have shown that guinea pigs ventilated with random variations in frequency and tidal volume had significantly larger pools of surfactant in the lung than animals ventilated in a monotonous manner. Here, we test the hypothesis that variable stretch patterns imparted on the AEII cells results in enhanced surfactant se...

  4. Vacuolar ATPase Regulates Surfactant Secretion in Rat Alveolar Type II Cells by Modulating Lamellar Body Calcium

    OpenAIRE

    Chintagari, Narendranath Reddy; Mishra, Amarjit; Su, Lijing; Wang, Yang; Ayalew, Sahlu; Hartson, Steven D; Liu, Lin

    2010-01-01

    Lung surfactant reduces surface tension and maintains the stability of alveoli. How surfactant is released from alveolar epithelial type II cells is not fully understood. Vacuolar ATPase (V-ATPase) is the enzyme responsible for pumping H+ into lamellar bodies and is required for the processing of surfactant proteins and the packaging of surfactant lipids. However, its role in lung surfactant secretion is unknown. Proteomic analysis revealed that vacuolar ATPase (V-ATPase) dominated the alveol...

  5. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment

    OpenAIRE

    Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; Boomershine, Chad S; Ortiz, Camila; Sherrill, Taylor P.; McMahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.; Lawson, William E.

    2011-01-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice tha...

  6. 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...

  7. CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis

    OpenAIRE

    Stromberg, Paul E.; Woolsey, Cheryl A.; Clark, Andrew T.; Clark, Jessica A.; Turnbull, Isaiah R.; McConnell, Kevin W.; Chang, Katherine C.; Chung, Chun-Shiang; Ayala., Alfred; Buchman, Timothy G; Hotchkiss, Richard S.; Coopersmith, Craig M.

    2009-01-01

    Lymphocytes help determine whether gut epithelial cells proliferate or differentiate but are not known to affect whether they live or die. Here, we report that lymphocytes play a controlling role in mediating gut epithelial apoptosis in sepsis but not under basal conditions. Gut epithelial apoptosis is similar in unmanipulated Rag-1−/− and wild-type (WT) mice. However, Rag-1−/− animals have a 5-fold augmentation in gut epithelial apoptosis following cecal ligation and puncture (CLP) compared ...

  8. Sequential development of apical-basal and planar polarities in aggregating epitheliomuscular cells of Hydra.

    Science.gov (United States)

    Seybold, Anna; Salvenmoser, Willi; Hobmayer, Bert

    2016-04-01

    Apical-basal and planar cell polarities are hallmarks of metazoan epithelia required to separate internal and external environments and to regulate trans- and intracellular transport, cytoskeletal organization, and morphogenesis. Mechanisms of cell polarization have been intensively studied in bilaterian model organisms, particularly in early embryos and cultured cells, while cell polarity in pre-bilaterian tissues is poorly understood. Here, we have studied apical-basal and planar polarization in regenerating (aggregating) clusters of epitheliomuscular cells of Hydra, a simple representative of the ancestral, pre-bilaterian phylum Cnidaria. Immediately after dissociation, single epitheliomuscular cells do not exhibit cellular polarity, but they polarize de novo during aggregation. Reestablishment of the Hydra-specific epithelial bilayer is a result of short-range cell sorting. In the early phase of aggregation, apical-basal polarization starts with an enlargement of the epithelial apical-basal diameter and by the development of belt-like apical septate junctions. Specification of the basal pole of epithelial cells occurs shortly later and is linked to synthesis of mesoglea, development of hemidesmosome-like junctions, and formation of desmosome-like junctions connecting the basal myonemes of neighbouring cells. Planar polarization starts, while apical-basal polarization is already ongoing. It is executed gradually starting with cell-autonomous formation, parallelization, and condensation of myonemes at the basal end of each epithelial cell and continuing with a final planar alignment of epitheliomuscular cells at the tissue level. Our findings reveal that epithelial polarization in Hydra aggregates occurs in defined steps well accessible by histological and ultrastructural techniques and they will provide a basis for future molecular studies. PMID:26921448

  9. Alveolar hypoventilation treated with medroxyprogesterone.

    OpenAIRE

    Milerad, J; Lagercrantz, H.; Löfgren, O

    1985-01-01

    Two children aged 1 and 20 months developed alveolar hypoventilation syndrome. They suffered severe apnoeic episodes and periodically required assisted ventilation. Their ventilatory response to carbon dioxide was lower than that of normal children and the transcutaneous oxygen tension during sleep was well below the normal range. Treatment with medroxyprogesterone acetate resulted in an improved response to carbon dioxide, and assisted ventilation was no longer needed. Oxygen and carbon diox...

  10. N-acetyl-L-cysteine inhibits adenoviral E1A-involved transactivation of nuclear factor-κB in rat alveolar epithelial cells%腺病毒E1A蛋白对核因子-κB活化的影响及N-乙酰半胱氨酸的干预作用

    Institute of Scientific and Technical Information of China (English)

    陈娟; 李冰; 冉丕鑫

    2010-01-01

    Objective The relationship between latent adenvorius infection and airway inflammation had not been well documented.The aim of this study was to illustrate the roles of adenovirus E1 A protein on the transactivation of NF-κ inflammatory stimuli and the effect of N-Acetylcysteine (NAC)upon the transactivation of NF-κB and AP-1 in cells stably expressing E1 A protein.Methods Rat alveolar epithelial cells stably expressing adenoviral E1 A or control plasmid were developed.For isolation of nuclear extracts,5×10~5 cells were plated and grown overnight in 60 mm dishes.Experiments were repeated 3 times.The cell model of stably expressing adenoviral E1 A was stimulated by LPS or TNF-aκ and treated with NAC,a precursor for cysteine.The NF-κB and AP-1 transcriptional activity were measured by LUC report system.The expression of NF-κB and AP-1 were measured by Western blot.Differences between groups were assessed for significance by Student't test,and multiple comparisons were made by one-way ANOVA.Results The luciferage activity drived by NF-κB element wag(9 698±98)RLU in untreated E1 A-positive clones and(101 195±234),and(170 385 4±443)RLU in LPS and TNF-α-stimulated cells,which were significantly higher than that of the control group 2 077±107,67 846±332,95 743-1-211 respectively.The luciferage activity drived by AP-1 element wag 9 034±78 RLU in untreated E1 A-positive clones and 26 343 4±398 and 31 731 4±332 RLU in LPS and TNF-α-stimulated cells.which were significantly higher than that of the control group 2 845±93,10 772±432,11 005±556 respectively.The densitometry of the NF-κB expression in E1 A-positive clones were 79.3±4.6 and 80.3±3.8 respectively without treatment and were 81.8 4±3.9-89.9±1.6 and 94.1 4-1.9 to 99.8±1.6 respectively under LPS or TNF-α stimulation,which were significantly higher than that of the control group(68.3±3.8,69.4±4.3 respectively)without stimulation and 70.1 4±2.8 to 80.8±3.6.73.4±4.9 to 83.2 4±6

  11. Quantitative Morphology of Epithelial Folds.

    Science.gov (United States)

    Štorgel, Nick; Krajnc, Matej; Mrak, Polona; Štrus, Jasna; Ziherl, Primož

    2016-01-01

    The shape of spatially modulated epithelial morphologies such as villi and crypts is usually associated with the epithelium-stroma area mismatch leading to buckling. We propose an alternative mechanical model based on intraepithelial stresses generated by differential tensions of apical, lateral, and basal sides of cells as well as on the elasticity of the basement membrane. We use it to theoretically study longitudinal folds in simple epithelia and we identify four types of corrugated morphologies: compact, invaginated, evaginated, and wavy. The obtained tissue contours and thickness profiles are compared to epithelial folds observed in invertebrates and vertebrates, and for most samples, the agreement is within the estimated experimental error. Our model establishes the groove-crest modulation of tissue thickness as a morphometric parameter that can, together with the curvature profile, be used to estimate the relative differential apicobasal tension in the epithelium. PMID:26745429

  12. Neuregulin-1-Human Epidermal Receptor-2 Signaling Is a Central Regulator of Pulmonary Epithelial Permeability and Acute Lung Injury*

    OpenAIRE

    Finigan, James H.; Faress, Jihane A.; Wilkinson, Emily; Mishra, Rangnath S.; Nethery, David E.; Wyler, David; Shatat, Mohammad; Ware, Lorraine B.; Matthay, Michael A.; Mason, Robert; Silver, Richard F.; Kern, Jeffrey A.

    2011-01-01

    The mechanisms behind the loss of epithelial barrier function leading to alveolar flooding in acute lung injury (ALI) are incompletely understood. We hypothesized that the tyrosine kinase receptor human epidermal growth factor receptor-2 (HER2) would be activated in an inflammatory setting and participate in ALI. Interleukin-1β (IL-1β) exposure resulted in HER2 activation in human epithelial cells and markedly increased conductance across a monolayer of airway epithelial cells. Upon HER2 bloc...

  13. 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

  14. [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

  15. [Anomalous systemic arterial supply to left basal lung with anomalous return of V6].

    Science.gov (United States)

    Yabuki, Hiroshi; Shibuya, Jotaro; Handa, Masashi; Yamada, Takehiro

    2014-11-01

    The patient was 52-year-old woman. Her chief compliant was bloody sputum. The computed tomography revealed an anomalous artery from descending aorta running into left lung basal segment and anomalous left V6 return to superior pulmonary vein. The bronchoscopic examination showed normal bronchial branches. Under the diagnosis of anomalous systemic arterial supply to left basal lung without sequestration, left lower lobectomy was performed. Microscopically, the pulmonary artery showed intimal thickening and alveolar collapse with interstitial fibrosis were seen. The postoperative course was uneventful and she discharged at 6th postoperative day. PMID:25391467

  16. 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

  17. 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.

  18. Diffuse pulmonary uptake of bone-seeking radiotracer in bone scintigraphy of a rare case of pulmonary alveolar microlithiasis

    International Nuclear Information System (INIS)

    Pulmonary alveolar microlithiasis (PAM) is a rare diffuse pulmonary disease representing microliths formed by deposition of calcium phosphonate in the alveolar airspaces. PAM is often diagnosed incidentally during chest X-ray imaging. Most of them are asymptomatic. We present a 39-year-old man referring for a bone scan due to a complaint of right leg pain. Bone scan showed diffuse uptake of bone-seeking radiotracer on both lung fields predominantly in basal regions. The bronchoalveolar lavage test confirmed the diagnosis of PAM

  19. OLETF大鼠肺泡上皮细胞基板的超微结构改变与定量检测%Ultrastrucural characteristics and morphometry of the alveolar epithelial basal lamina in Otsuka Long-Evans Tokushima fatty rats

    Institute of Scientific and Technical Information of China (English)

    汤秀英; 王书合; 柴立军

    2009-01-01

    目的 观察自发性2型糖尿病OLETF(Otsuka Long-Evans Tokushima Fatty)大鼠肺泡上皮细胞基板的超微结构改变.方法 用透射电镜观察、图像分析仪及形态计量学方法计算OLETF及对照的LETO(Long-Evans Tokushima Otsuka)大鼠肺泡上皮细胞基板的超微结构及厚度.结果 与LETO组大鼠相比,OLETF组大鼠肺泡毛细血管内皮细胞基板与Ⅰ型肺泡上皮细胞基板融合部及Ⅱ型肺泡上皮细胞基板均增厚(分别为110.6±14.14 vs.57.3±11.08和116.4±10.22 vs.71.89±7.68,P<0.01).结论 OLETF大鼠肺泡上皮细胞基板增厚,提示可能与糖尿病高血糖环境引起毛细血管基板成分发生改变有关.

  20. 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.)

  1. 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.)

  2. 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.)

  3. 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.)

  4. Epithelial cell apoptosis causes acute lung injury masquerading as emphysema.

    Science.gov (United States)

    Mouded, Majd; Egea, Eduardo E; Brown, Matthew J; Hanlon, Shane M; Houghton, A McGarry; Tsai, Larry W; Ingenito, Edward P; Shapiro, Steven D

    2009-10-01

    Theories of emphysema traditionally revolved around proteolytic destruction of extracellular matrix. Models have recently been developed that show airspace enlargement with the induction of pulmonary cell apoptosis. The purpose of this study was to determine the mechanism by which a model of epithelial cell apoptosis caused airspace enlargement. Mice were treated with either intratracheal microcystin (MC) to induce apoptosis, intratracheal porcine pancreatic elastase (PPE), or their respective vehicles. Mice from all groups were inflated and morphometry was measured at various time points. Physiology measurements were performed for airway resistance, tissue elastance, and lung volumes. The groups were further analyzed by air-saline quasistatic measurements, surfactant staining, and surfactant functional studies. Mice treated with MC showed evidence of reversible airspace enlargement. In contrast, PPE-treated mice showed irreversible airspace enlargement. The airspace enlargement in MC-treated mice was associated with an increase in elastic recoil due to an increase in alveolar surface tension. PPE-treated mice showed a loss of lung elastic recoil and normal alveolar surface tension, a pattern more consistent with human emphysema. Airspace enlargement that occurs with the MC model of pulmonary epithelial cell apoptosis displays physiology distinct from human emphysema. Reversibility, restrictive physiology due to changes in surface tension, and alveolar enlargement associated with heterogeneous alveolar collapse are most consistent with a mild acute lung injury. Inflation near total lung capacity gives the appearance of enlarged alveoli as neighboring collapsed alveoli exert tethering forces. PMID:19188661

  5. Capsaicinoids Cause Inflammation and Epithelial Cell Death through Activation of Vanilloid Receptors

    OpenAIRE

    Reilly, Christopher A.; Taylor, Jack L.; Lanza, Diane L.; Carr, Brian A.; Crouch, Dennis J.; Yost, Garold S.

    2003-01-01

    Capsaicinoids, found in less-than-lethal self-defense weapons, have been associated with respiratory failure and death in exposed animals and people. The studies described herein provide evidence for acute respiratory inflammation and damage to epithelial cells in experimental animals, and provide precise molecular mechanisms that mediate these effects using human bronchiolar and alveolar epithelial cells. Inhalation exposure of rats to pepper sprays (capsaicinoids) produced acute inflammatio...

  6. IDIOPATHIC PULMONARY FIBROSIS: A DISORDER OF EPITHELIAL CELL DYSFUNCTION

    OpenAIRE

    Zoz, Donald F.; Lawson, William E.; Blackwell, Timothy S.

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea, interstitial infiltrates in lung parenchyma, and restriction on pulmonary function testing. IPF is the most common and severe of the idiopathic interstitial pneumonias (IIPs), with most individuals progressing to respiratory failure. Multiple lines of evidence reveal prominent roles for alveolar epithelial cells (AECs) in disease. Our current disease paradigm is that ongoing or repetitive injurious stimuli in the pre...

  7. Alveolar derecruitment and collapse induration as crucial mechanisms in lung injury and fibrosis.

    Science.gov (United States)

    Lutz, Dennis; Gazdhar, Amiq; Lopez-Rodriguez, Elena; Ruppert, Clemens; Mahavadi, Poornima; Günther, Andreas; Klepetko, Walter; Bates, Jason H; Smith, Bradford; Geiser, Thomas; Ochs, Matthias; Knudsen, Lars

    2015-02-01

    Idiopathic pulmonary fibrosis (IPF) and bleomycin-induced pulmonary fibrosis are associated with surfactant system dysfunction, alveolar collapse (derecruitment), and collapse induration (irreversible collapse). These events play undefined roles in the loss of lung function. The purpose of this study was to quantify how surfactant inactivation, alveolar collapse, and collapse induration lead to degradation of lung function. Design-based stereology and invasive pulmonary function tests were performed 1, 3, 7, and 14 days after intratracheal bleomycin-instillation in rats. The number and size of open alveoli was correlated to mechanical properties. Active surfactant subtypes declined by Day 1, associated with a progressive alveolar derecruitment and a decrease in compliance. Alveolar epithelial damage was more pronounced in closed alveoli compared with ventilated alveoli. Collapse induration occurred on Day 7 and Day 14 as indicated by collapsed alveoli overgrown by a hyperplastic alveolar epithelium. This pathophysiology was also observed for the first time in human IPF lung explants. Before the onset of collapse induration, distal airspaces were easily recruited, and lung elastance could be kept low after recruitment by positive end-expiratory pressure (PEEP). At later time points, the recruitable fraction of the lung was reduced by collapse induration, causing elastance to be elevated at high levels of PEEP. Surfactant inactivation leading to alveolar collapse and subsequent collapse induration might be the primary pathway for the loss of alveoli in this animal model. Loss of alveoli is highly correlated with the degradation of lung function. Our ultrastructural observations suggest that collapse induration is important in human IPF. PMID:25033427

  8. Sds22, a PP1 phosphatase regulatory subunit, regulates epithelial cell polarity and shape [Sds22 in epithelial morphology

    OpenAIRE

    Sung Hsin-Ho; Fletcher Georgina; Hidalgo Cristina; Grusche Felix A; Sahai Erik; Thompson Barry J

    2009-01-01

    Abstract Background How epithelial cells adopt their particular polarised forms is poorly understood. In a screen for genes regulating epithelial morphology in Drosophila, we identified sds22, a conserved gene previously characterised in yeast. Results In the columnar epithelia of imaginal discs or follicle cells, mutation of sds22 causes contraction of cells along their apical-basal axis, resulting in a more cuboidal morphology. In addition, the mutant cells can also display altered cell pol...

  9. Experimental radiation pneumonitis. Corticosteroids increase the replicative activity of alveolar type 2 cells

    International Nuclear Information System (INIS)

    Corticosteroid administration during radiation pneumonitis in mice markedly improves the physiologic abnormalities and decreases mortality, an effect that has been attributed to the stimulation of surfactant synthesis and secretion by type 2 alveolar epithelial cells. In the present experiments we explored the effects of corticosteroids on the replicative activity of type 2 cells of lethally irradiated lungs at the height of the radiation reaction. The labeling index of type 2 cells of irradiated mice was increased threefold above that of sham-irradiated controls. Corticosteroids given continuously from 10 weeks after thoracic irradiation further increased the type 2 cell labeling index another threefold above that of irradiated untreated mice. The enhanced reproductive activity of type 2 cells following thoracic irradiation is seen as a protective response that is augmented by corticosteroids, whose effect may be both to improve the physiology of the alveolar surface and to maintain the population of alveolar epithelial cells. The bearing of this result on the controversial role of the type 2 cell as a target in radiation pneumonitis is discussed

  10. CBX7 deficiency plays a positive role in dentin and alveolar bone development.

    Science.gov (United States)

    Zhou, Zhixuan; Yin, Ying; Jiang, Fei; Niu, Yuming; Wan, Shujian; Chen, Ning; Shen, Ming

    2016-08-01

    To clarify the role of CBX7 deficiency in dentin and alveolar bone development, the dental and mandibular phenotypes of homozygous CBX7-knockout (CBX7(-/-)) mice were compared with their wild-type (WT) counterparts at 3 weeks age. In contrast to WT littermates, dental volume and dentin sialoprotein-positive area were significantly increased, whereas the area ratio of predentin to dentin was decreased markedly in CBX7(-/-) mice. Mineral density, cortical thickness, alveolar bone volume, type I collagen and osterix-immunopositive area, osteoblast number and activity, protein expression and mRNA level of Runt-related transcription factor 2 (Runx2), alkaline phosphatase, osteocalcin, osteopontin and bone morphogenetic protein 2 (BMP2) were all remarkably increased, while osteoclast number and activity, and mRNA expression ratio of NF-κB ligand (RANKL) to osteoprotegerin (opg) were all decreased significantly in the alveolar bone of CBX7(-/-) mice compared with their WT counterparts. Moreover, proliferating cell nuclear antigen (PCNA)-positive cells were found more in Hertwig' s epithelial root sheath of CBX7(-/-) mice, and their protein level of cyclin E1, cyclin-dependent kinase 2 (CDK2) were correspondingly increased in contrast to WT mice. Taken together, these results of this study suggest that CBX7 deficiency plays a positive role in dentin and alveolar bone formation. PMID:27271093

  11. Cardiovascular effects of basal insulins

    Directory of Open Access Journals (Sweden)

    Mannucci E

    2015-07-01

    Full Text Available Edoardo Mannucci,1 Stefano Giannini,2 Ilaria Dicembrini1 1Diabetes Agency, Careggi Teaching Hospital, Florence, 2Section of Endocrinology, Department of Biomedical Clinical and Experimental Sciences, University of Florence and Careggi University Hospital, Florence, Italy Abstract: Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane and basal insulin analogs (glargine, detemir, and the more recent degludec differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with

  12. 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)

  13. Pulmonary administration of phosphoinositide 3-kinase inhibitor is a curative treatment for chronic obstructive pulmonary disease by alveolar regeneration.

    Science.gov (United States)

    Horiguchi, Michiko; Oiso, Yuki; Sakai, Hitomi; Motomura, Tomoki; Yamashita, Chikamasa

    2015-09-10

    Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease, causing widespread and irreversible alveoli collapse. The discovery of a low-molecular-weight compound that induces regeneration of pulmonary alveoli is of utmost urgency to cure intractable pulmonary diseases such as COPD. However, a practically useful compound for regenerating pulmonary alveoli is yet to be reported. Previously, we have elucidated that Akt phosphorylation is involved in a differentiation-inducing molecular mechanism of human alveolar epithelial stem cells, which play a role in regenerating pulmonary alveoli. In the present study, we directed our attention to phosphoinositide 3-kinase (PI3K)-Akt signaling and examined whether PI3K inhibitors display the pulmonary alveolus regeneration. Three PI3K inhibitors with different PI3K subtype specificities (Wortmannin, AS605240, PIK-75 hydrochloride) were tested for the differentiation-inducing effect on human alveolar epithelial stem cells, and Wortmannin demonstrated the most potent differentiation-inducing activity. We evaluated Akt phosphorylation in pulmonary tissues of an elastase-induced murine COPD model and found that Akt phosphorylation in the pulmonary tissue was enhanced in the murine COPD model compared with normal mice. Then, the alveolus-repairing effect of pulmonary administration of Wortmannin to murine COPD model was evaluated using X-ray CT analysis and hematoxylin-eosin staining. As a result, alveolar damages were repaired in the Wortmannin-administered group to a similar level of normal mice. Furthermore, pulmonary administration of Wortmannin induced a significant recovery of the respiratory function, compared to the control group. These results indicate that Wortmannin is capable of inducing differentiation of human alveolar epithelial stem cells and represents a promising drug candidate for curative treatment of pulmonary alveolar destruction in COPD. PMID:26160307

  14. [Anti-basal ganglia antibody].

    Science.gov (United States)

    Hayashi, Masaharu

    2013-04-01

    Sydenham's chorea (SC) is a major manifestation of rheumatic fever, and the production of anti-basal ganglia antibodies (ABGA) has been proposed in SC. The pathogenesis is hypothesized as autoimmune targeting of the basal ganglia via molecular mimicry, triggered by streptococcal infection. The spectrum of diseases in which ABGA may be involved has been broadened to include other extrapyramidal movement disorders, such as tics, dystonia, and Parkinsonism, as well as other psychiatric disorders. The autoimmune hypothesis in the presence and absence of ABGA has been suggested in Tourette's syndrome (TS), early onset obsessive-compulsive disorders (OCD), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Recently, the relationship between ABGA and dopamine neurons in the basal ganglia has been examined, and autoantibodies against dopamine receptors were detected in the sera from patients with basal ganglia encephalitis. In Japan, the occurrence of subacute encephalitis, where patients suffer from episodes of altered behavior and involuntary movements, has increased. Immune-modulating treatments are effective, indicating the involvement of an autoimmune mechanism. We aimed to detect the anti-neuronal autoantibodies in such encephalitis, using immunohistochemical assessment of patient sera. The sera from patients showing involuntary movements had immunoreactivity for basal ganglia neurons. Further epitopes for ABGA will be investigated in basal ganglia disorders other than SC, TS, OCD, and PANDAS. PMID:23568985

  15. Isolation, separation, and characterization of epithelial and connective cells from rat palate

    Energy Technology Data Exchange (ETDEWEB)

    Terranova, Victor Paul

    1979-01-01

    Epithelial and connective tissue cells were isolated from rat palate by sequential collagenase, hyaluronidase and trypsin digestion of the extracellular matrix. Differences between the two populations were noted with respect to total cell protein, total cell water, proline uptake and incorporation, percent collagen synthesized, effects of parathyroid hormone, metabolism of D-valine and cell density. Basal epithelial cells were subsequently separated from the heterogeneous epithelial cell population on shallow linear density gradients by velocity centrifugation. The type of collagen synthesized by the basal epithelial cells was compared to the type of collagen synthesized by the connective tissue cells by means of labeled amino acid incorporation ratios. Cells isolated from the epithelial and connective tissue were compared. From these studies it can be concluded that epithelial and connective tissue cells can be isolated from rat palate as viable and distinct populations with respect to the biochemical parameters examined. Furthermore, subpopulations can be separated and biochemically characterized.

  16. A Case Report of Syringocystadenoma Papilliferum Mimicking Basal Cell Carcinoma on the Face

    Directory of Open Access Journals (Sweden)

    Engin Sezer

    2012-03-01

    Full Text Available Syringocystadenoma papilliferum is clinically characterized by verrucous nodules or plaques, mainly observed on the scalp during childhood. Histopathologically, epidermal invagination showing luminal epithelial cells with decapitation secretion is diagnostic. Herein, we describe an unusual late-onset case of syringocystadenoma papilliferum mimicking basal cell carcinoma on the face.

  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. The role of intraalveolar fibrosis in the process of pulmonary structural remodeling in patients with diffuse alveolar damage.

    OpenAIRE

    Y. Fukuda(Miyagi University of Education); Ishizaki, M; Masuda, Y; Kimura, G.; Kawanami, O.; Masugi, Y.

    1987-01-01

    For a study of the processes and mechanisms of pulmonary structural remodeling in fibrotic lungs and metaplastic squamous epithelial cells in fibrotic alveoli, immunohistochemical, ultrastructural, and light-microscopic morphometric observations were made of the lungs in acute and proliferative stages of diffuse alveolar damage (n = 40) obtained from biopsies and autopsies. Morphometry showed that intraalveolar fibrosis developed in the early proliferative stage and was more prominent than in...

  19. SGLT1 activity in lung alveolar cells of diabetic rats modulates airway surface liquid glucose concentration and bacterial proliferation

    OpenAIRE

    Tales Lyra Oliveira; Návylla Candeia-Medeiros; Polliane M. Cavalcante-Araújo; Igor Santana Melo; Elaine Fávaro-Pípi; Luciana Alves Fátima; Antônio Augusto Rocha; Luiz Ricardo Goulart; Ubiratan Fabres Machado; Ruy R. Campos; Robinson Sabino-Silva

    2016-01-01

    High glucose concentration in the airway surface liquid (ASL) is an important feature of diabetes that predisposes to respiratory infections. We investigated the role of alveolar epithelial SGLT1 activity on ASL glucose concentration and bacterial proliferation. Non-diabetic and diabetic rats were intranasally treated with saline, isoproterenol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity); 2 hours later, glucose concentration and bacterial proliferation (methicillin-...

  20. Recurrent peripheral odontogenic fibroma associated with basal cell budding

    Directory of Open Access Journals (Sweden)

    C Sreeja

    2014-01-01

    Full Text Available Peripheral odontogenic fibroma (POdF is a rare benign odontogenic neoplasm. It represents the soft tissue counterpart of central odontogenic fibroma. The embryonic source of POdF has been suggested by many as arising from the rest of dental lamina that has persisted in the gingiva following its disintegration. It presents clinically as a firm, slow growing and sessile gingival mass, which is difficult to distinguish with more common inflammatory lesions. Very few cases of recurrence have been documented. It has been stated that histological budding of basal cell layer of the surface squamous epithelium is associated with higher recurrence and the presence of calcification in direct apposition to the epithelial rest is associated with lower recurrence. Hereby, we present a case which histologically exhibited budding of the basal cell layer, which could have been the reason for its recurrence.

  1. Cardiovascular effects of basal insulins.

    Science.gov (United States)

    Mannucci, Edoardo; Giannini, Stefano; Dicembrini, Ilaria

    2015-01-01

    Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane) and basal insulin analogs (glargine, detemir, and the more recent degludec) differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with regard to cardiovascular safety will provide definitive evidence. PMID:26203281

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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 ...

  8. Polarized Integrin Mediates Human Keratinocyte Adhesion to Basal Lamina

    Science.gov (United States)

    de Luca, Michele; Tamura, Richard N.; Kajiji, Shama; Bondanza, Sergio; Rossino, Paola; Cancedda, Ranieri; Carlo Marchisio, Pier; Quaranta, Vito

    1990-09-01

    Epithelial cell interactions with matrices are critical to tissue organization. Indirect immunofluorescence and immunoprecipitations of cell lysates prepared from stratified cultures of human epidermal cells showed that the major integrins expressed by keratinocytes are α_Eβ_4 (also called α_6β_4) and α_2β_1/α_3β_1. The α_Eβ_4 integrin is localized at the surface of basal cells in contact with the basement membrane, whereas α_2β_1/ α_3β_1 integrins are absent from the basal surface and are localized only on the lateral surface of basal and spinous keratinocytes. Anti-β_4 antibodies potently inhibited keratinocyte adhesion to matrigel or purified laminin, whereas anti-β_1 antibodies were ineffective. Only anti-β_4 antibodies were able to detach established keratinocyte colonies. These data suggest that α_Eβ_4 mediates keratinocyte adhesion to basal lamina, whereas the β_1 subfamily is involved in cell-cell adhesion of keratinocytes.

  9. Hepatocyte growth factor is produced by blood and alveolar neutrophils in acute respiratory failure.

    Science.gov (United States)

    Jaffré, Sandrine; Dehoux, Monique; Paugam, Catherine; Grenier, Alain; Chollet-Martin, Sylvie; Stern, Jean-Baptiste; Mantz, Jean; Aubier, Michel; Crestani, Bruno

    2002-02-01

    We tested the novel hypothesis that neutrophils in the lung or the airspaces may produce hepatocyte growth factor (HGF) in ventilated patients with acute respiratory failure. Neutrophils were purified from blood and bronchoalveolar lavage (BAL) fluid samples from 16 mechanically ventilated patients who underwent BAL for a diagnostic workup of ventilator-acquired pneumonia. Most of the patients had pneumonia (n = 11). Ten nonventilated patients served as controls. Both blood and BAL neutrophils released HGF in vitro. Basal HGF secretion by blood neutrophils from controls was 823 (666) pg x ml(-1) x 10(-7) neutrophils (median, 25th-75th percentile) and doubled to 1,730 (1,684-2,316) pg x ml(-1) x 10(-7) neutrophils (P = 0.001) with lipopolysaccharide (LPS) stimulation. Basal HGF secretion by blood neutrophils from patients was similar [956 (655-2,140) pg x ml(-1) x 10(-7) neutrophils, P = 0.4] and doubled with LPS stimulation [2,767 (2,165-3,688) pg x ml(-1) x 10(-7) neutrophils, P < 0.0001 vs. controls]. Alveolar neutrophils released HGF in vitro [653 (397-1,209) pg x ml(-1) x 10(-7) neutrophils]. LPS stimulation did not significantly increase the HGF release from alveolar neutrophils [762 (434-1,305) pg x ml(-1) x 10(-7) neutrophils]. BAL HGF positively correlated with the BAL neutrophil count (P = 0.01, R = 0.58). We conclude that blood and alveolar neutrophils from patients with acute respiratory failure can produce HGF, a mitogenic factor that may enhance the alveolar repair process. PMID:11792636

  10. AIRWAY EPITHELIAL CELL RESPONSE TO HUMAN METAPNEUMOVIRUS INFECTION

    Science.gov (United States)

    X, Bao; T, Liu; L, Spetch; D, Kolli; R.P, Garofalo; A, Casola

    2007-01-01

    Human metapneumovirus (hMPV) is a major cause of lower respiratory tract infections (LRTIs) in infants, elderly and immunocompromised patients. In this study, we show that hMPV can infect in a similar manner epithelial cells representative of different tracts of the airways. hMPV-induced expression of chemokines IL-8 and RANTES in primary small alveolar epithelial cells (SAE) and in a human alveolar type II-like epithelial cell line (A549) was similar, suggesting that A549 cells can be used as a model to study lower airway epithelial cell responses to hMPV infection. A549 secreted a variety of CXC and CC chemokines, cytokines and type I interferons, following hMPV infection. hMPV was also a strong inducer of transcription factors belonging to nuclear factor (NF)-κB, interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) families, which are known to orchestrate the expression of inflammatory and immuno-modulatory mediators. PMID:17655903

  11. 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

  12. 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.

  13. The influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction in rats.

    Science.gov (United States)

    Dias-da-Silva, Marco A; Pereira, Andresa C; Marin, Miguel Cc; Salgado, Miguel Ac

    2013-10-01

    The Copaiba oil has been used as an auxiliary treatment of inflammations, skin disorders and stomach ulcers, however, in dentistry, this "alternative" medicine has not been investigated yet. The purpose of this study was to evaluate the influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction. Twenty-eight wistar male rats had their lower first molar teeth extracted. Subsequently, they were divided in four groups, according to the treatment performed: (a) alveolar socket irrigation with copaiba oil; (b) alveolar socket irrigation with physiological serum; (c) daily gavage with copaiba oil or (d) daily gavage with physiological serum. After the sacrifice, the mandibles were removed and processed in order to obtain decalcified histological sections. The results demonstrated high level of epithelial migration, small number of inflammatory cells and vascular enhancement in the animals which received systemic administration of copaiba oil. The rats treated with topic administration of copaiba oil presented ulcerations and large number of inflammatory cells. An increased bone neoformation was observed in both groups treated with copaiba oil when compared with placebo group. It could be concluded that topic or systemic administration of copaiba oil leads to a better alveolar bone healing, however the topic application on connective tissue should be carefully considered, regarding the whole socket wound healing. Key words:Alveolar wound healing, oil-resin, copaiba. PMID:24455075

  14. Early Stages of Hyaline Membrane Formation Detected in Alveolar Mouths in Diffuse Alveolar-Damage-Associated Diseases: A Detailed Immunohistochemical Study.

    Science.gov (United States)

    Ohtsuki, Yuji; Fujita, Jiro; Yoshinouchi, Takeo; Enzan, Hideaki; Iguchi, Mitsuko; Lee, Gang-Hong; Furihata, Mutsuo

    2015-10-01

    To study the early stages of hyaline membrane (HM) formation, diffuse alveolar damage (DAD) was thoroughly investigated using immunohistochemical methods in 15 autopsy cases, which consisted of various types of interstitial pneumonias and pulmonary diseases derived from nonmalignant or malignant diseases. Alveolar mouths (AMs) that were presumed to be normal were ultrastructurally examined in detail, by using pulmonary tissues in the pneumothorax. It is interesting to note that during the initial stages of HM formation in AMs, fragmented eosinophilic masses were closely attached to AMs as irregular fragments or by a cap-like structure. The ultrastructure revealed some distance between the capillary spaces and surface epithelium of the AMs, indicating that the epithelial cells at the AMs might be often easily damaged even by minor stimuli; they can be considered as "locus minoris resistentiae." HMs were found to be formed initially at the site of AMs derived from fragmented eosinophilic masses in not only pulmonary but also extrapulmonary diseases, including both nonmalignant and malignant diseases. These irregular eosinophilic masses, representing the early shape of HMs, were immunohistochemically positive for the epithelial membrane antigens, namely, surfactant protein A and factor VIII antigen, and occasionally for KL-6 and cytokeratins. These results suggested that fragmented irregular masses represent the initial phase of HM formation. Five of 15 cases were focally negative for KL-6 at the initial irregular mass of HMs. Because KL-6 is one of the fundamental components of pulmonary surface elements, it needs to be studied further by detailed clinicopathological examination. PMID:26183849

  15. 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...

  16. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Ar [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Chung, Jin Sil [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Cho, Sang-Ho [Department of Pathology, Pochon CHA University, College of Medicine, Gyeonggi-do (Korea, Republic of); Kim, Hyung Jung, E-mail: khj57@yuhs.ac.kr [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Yoo, Young Do, E-mail: ydy1130@korea.ac.kr [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

    2013-09-20

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H{sub 2}O{sub 2}) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H{sub 2}O{sub 2} treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.

  17. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    International Nuclear Information System (INIS)

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H2O2) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H2O2 treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells

  18. Alveolar ridge augmentation with titanium mesh. A retrospective clinical study.

    Science.gov (United States)

    Poli, Pier P; Beretta, Mario; Cicciù, Marco; Maiorana, Carlo

    2014-01-01

    An adequate amount of bone all around the implant surface is essential in order to obtain long-term success of implant restoration. Several techniques have been described to augment alveolar bone volume in critical clinical situations, including guided bone regeneration, based on the use of barrier membranes to prevent ingrowth of the epithelial and gingival connective tissue cells. To achieve this goal, the use of barriers made of titanium micromesh has been advocated. A total of 13 patients were selected for alveolar ridge reconstruction treatment prior to implant placement. Each patient underwent a tridimensional bone augmentation by means of a Ti-mesh filled with intraoral autogenous bone mixed with deproteinized anorganic bovine bone in a 1:1 ratio. Implants were placed after a healing period of 6 months. Panoramic x-rays were performed after each surgical procedure and during the follow-up recalls. Software was used to measure the mesial and the distal peri-implant bone loss around each implant. The mean peri-implant bone loss was 1.743 mm on the mesial side and 1.913 mm on the distal side, from the top of the implant head to the first visible bone-implant contact, at a mean follow-up of 88 months. The use of Ti-mesh allows the regeneration of sufficient bone volume for ideal implant placement. The clinical advantages related to this technique include the possibility of correcting severe vertical atrophies associated with considerable reductions in width and the lack of major complications if soft-tissue dehiscence and mesh exposures do occur. PMID:25317209

  19. 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.

  20. 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.

  1. Cryotherapy in basal cell carcinoma

    OpenAIRE

    Sandra A; Balachandran C; Shenoi S; Sabitha L; Pai Satish; Ravikumar B; Roy Alfred

    1999-01-01

    Cryotherapy has proved to be an effective tool in the management of various dermatoses. We report 6 patients with histopathologically proven basal cell carcinoma of variable sizes treated with liquid nitrogen cryotherapy by the open spray technique. Lesions tended to heal with depigmentation and scar formation. However depigmented areas often repigmented over a period of time.

  2. Loss of p120 catenin aggravates alveolar edema of ventilation induced lung injury

    Institute of Scientific and Technical Information of China (English)

    DAI Chen-yang; DAI Guo-feng; SUN Yu; WANG Yue-lan

    2013-01-01

    Background p120 catenin (p120ctn) is an adheren junction protein that regulates barrier function,but its role has not been explored in alveolar edema induced by ventilation.We measured stretch-induced cell gap formation in MLE 12 cells due to the loss of p120.We hypothesized that alveolar permeability was increased by high lung inflation associated with alveolar epithelia cell tight junctions being destroyed,which resulted from the loss of p120.Methods Cultured MLE12 cells were subjected to being stretched or un-stretched (control) and some cells were pretreated with pp2 (c-src inhibitor).After the end of stretching for 0,1,2,and 4 hours,the cells were lysed,and p120 expression and c-src activation was determined by Western blotting analysis.In vivo,SD rats were taken to different tidal volumes (Vt 7 ml/kg or 40 ml/kg,PEEP=0,respiratory rate 30-40 betas/min) for 0,1,2,and 4 hour and some were pretreated with pp2,and alveolar edema was calculated.Rerults It was found that p120 expression was reduced and c-src activation increased in a time-dependent and strain-dependent manner due to cyclic-stretch of the alveolar epithelial cells.These changes could be reversed by inhibition of c-src.We obtained similar changes in rats when they were subjected to large tidal volumes and the alveolar edema increased more than in rats in the low Vt group.Pretreated the rats with inhibition of c-src had less pulmonary edema induced by the high tidal volume ventilation.Conclusions Cyclic stretch MLE 12 cells induced the loss of p120 and may be the same reason by high tidal volume ventilation in rats can aggravate alveolar edema.Maintenance of p120 expression may be a novel therapeutic strategy for the prevention and treatment of ventilation induced lung injury (VILI).

  3. 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

  4. 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.

  5. 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

  6. Acute respiratory bronchiolitis: an ultrastructural and autoradiographic study of epithelial cell injury and renewal in Rhesus monkeys exposed to ozone

    International Nuclear Information System (INIS)

    The pathogenesis of acute respiratory bronchiolitis was examined in Rhesus monkeys exposed to 0.8 ppM ozone for 4 to 50 hours. Epithelial injury and renewal were qualitatively and quantitatively characterized by correlated techniques of scanning and transmission electron microscopy as well as by light-microscopic autoradiography following labeling with tritiated thymidine. Extensive degeneration and necrosis of Type 1 epithelial cells occurred on the respiratory bronchiolar wall during the initial 4 to 12 hours of exposure. Increased numbers of labeled epithelial cells were present in this region after 18 hours of exposure, and the highest labeling index (18%) was measured after 50 hours of exposure. Most (67 to 80%) of the labeled cells and all the mitotic epithelial cells (22) observed ultrastructurally were cuboidal bronchiolar epithelial cells. Of the labeled epithelial cells, 20 to 33% were Type 2 epithelial cells. After 50 hours of exposure the respiratory bronchiolar epithelium was hyperplastic. The predominant inflammatory cell in respiratory bronchiolar exudate was the alveolar macrophage. Monkeys that were exposed for 50 hours and allowed to recover in unozonized air for 7 days had incomplete resolution of respiratory bronchiolar epithelial hyperplasia. The results indicate that Type 1 epithelial cells lining respiratory bronchioles are the cell types most sensitive to injury and that both cuboidal bronchiolar epithelial cells and Type 2 epithelial cells function as stem cells in epithelial renewal

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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...

  14. Karsinoma Sel Basal Pada Wajah

    OpenAIRE

    Hastuti

    2008-01-01

    Karsinoma sel basal merupakan tumor ganas pada lapisan epidermis kulit yang paling umum dijumpai. Lokasi tumor iui paling banyak pada wajah dibandingkan anggota tubuh lainnya. Etiologi tumor iui diduga berhubungan dengan cahaya matahari yang mengandung sinar ultraviolet yang karsinogenik. Klasifikasi tumor ini dibagi berdasarkan gambaran kliuis dan histopatologisnya. Diagnosa tumor ini dapat ditegakkan dengan pemeriksaan k1inis dan histologis, pemeriksaan radiologis jarang digunakan. Diag...

  15. Ancestral vascular lumen formation via basal cell surfaces.

    Directory of Open Access Journals (Sweden)

    Tomás Kucera

    Full Text Available The cardiovascular system of bilaterians developed from a common ancestor. However, no endothelial cells exist in invertebrates demonstrating that primitive cardiovascular tubes do not require this vertebrate-specific cell type in order to form. This raises the question of how cardiovascular tubes form in invertebrates? Here we discovered that in the invertebrate cephalochordate amphioxus, the basement membranes of endoderm and mesoderm line the lumen of the major vessels, namely aorta and heart. During amphioxus development a laminin-containing extracellular matrix (ECM was found to fill the space between the basal cell surfaces of endoderm and mesoderm along their anterior-posterior (A-P axes. Blood cells appear in this ECM-filled tubular space, coincident with the development of a vascular lumen. To get insight into the underlying cellular mechanism, we induced vessels in vitro with a cell polarity similar to the vessels of amphioxus. We show that basal cell surfaces can form a vascular lumen filled with ECM, and that phagocytotic blood cells can clear this luminal ECM to generate a patent vascular lumen. Therefore, our experiments suggest a mechanism of blood vessel formation via basal cell surfaces in amphioxus and possibly in other invertebrates that do not have any endothelial cells. In addition, a comparison between amphioxus and mouse shows that endothelial cells physically separate the basement membranes from the vascular lumen, suggesting that endothelial cells create cardiovascular tubes with a cell polarity of epithelial tubes in vertebrates and mammals.

  16. Basal body structure in Trichonympha.

    Science.gov (United States)

    Guichard, Paul; Gönczy, Pierre

    2016-01-01

    Trichonympha is a symbiotic flagellate of many species of termites and of the wood-feeding cockroach. Remarkably, this unicellular organism harbors up to over ten thousand flagella on its surface, which serve to propel it through the viscous environment of the host hindgut. In the 1960s, analysis of resin-embedded Trichonympha samples by electron microscopy revealed that the basal bodies that give rise to these flagella are exceptionally long, with a proximal, cartwheel-bearing, region some 50 times longer than that of regular centrioles. In recent years, this salient feature has prompted the analysis of the 3D architecture of Trichonympha basal bodies in the native state using cryo-electron tomography. The resulting ~40 Å resolution map of the basal body proximal region revealed a number of novel features that may be conserved in centrioles of other systems. These include proximal-distal polarity of the pinhead structure that links the cartwheel to centriolar microtubules, as well as of the linker between the A and the C microtubules. Moreover, this work demonstrated that the cartwheel is made of stacked ring-like structures that likely each comprise 18 molecules of SAS-6 proteins. PMID:26937279

  17. Jamming dynamics of stretch-induced surfactant release by alveolar type II cells.

    Science.gov (United States)

    Majumdar, Arnab; Arold, Stephen P; Bartolák-Suki, Erzsébet; Parameswaran, Harikrishnan; Suki, Béla

    2012-03-01

    Secretion of pulmonary surfactant by alveolar epithelial type II cells is vital for the reduction of interfacial surface tension, thus preventing lung collapse. To study secretion dynamics, rat alveolar epithelial type II cells were cultured on elastic membranes and cyclically stretched. The amounts of phosphatidylcholine, the primary lipid component of surfactant, inside and outside the cells, were measured using radiolabeled choline. During and immediately after stretch, cells secreted less surfactant than unstretched cells; however, stretched cells secreted significantly more surfactant than unstretched cells after an extended lag period. We developed a model based on the hypothesis that stretching leads to jamming of surfactant traffic escaping the cell, similar to vehicular traffic jams. In the model, stretch increases surfactant transport from the interior to the exterior of the cell. This transport is mediated by a surface layer with a finite capacity due to the limited number of fusion pores through which secretion occurs. When the amount of surfactant in the surface layer approaches this capacity, interference among lamellar bodies carrying surfactant reduces the rate of secretion, effectively creating a jam. When the stretch stops, the jam takes an extended time to clear, and subsequently the amount of secreted surfactant increases. We solved the model analytically and show that its dynamics are consistent with experimental observations, implying that surfactant secretion is a fundamentally nonlinear process with memory representing collective behavior at the level of single cells. Our results thus highlight the importance of a jamming dynamics in stretch-induced cellular secretory processes. PMID:22033531

  18. 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.

  19. Exogenous hydrogen sulfide (H2S protects alveolar growth in experimental O2-induced neonatal lung injury.

    Directory of Open Access Journals (Sweden)

    Arul Vadivel

    Full Text Available BACKGROUND: Bronchopulmonary dysplasia (BPD, the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension (PHT. Currently there is no specific treatment for BPD. Hydrogen sulfide (H2S, carbon monoxide and nitric oxide (NO, belong to a class of endogenously synthesized gaseous molecules referred to as gasotransmitters. While inhaled NO is already used for the treatment of neonatal PHT and currently tested for the prevention of BPD, H2S has until recently been regarded exclusively as a toxic gas. Recent evidence suggests that endogenous H2S exerts beneficial biological effects, including cytoprotection and vasodilatation. We hypothesized that H2S preserves normal alveolar development and prevents PHT in experimental BPD. METHODS: We took advantage of a recently described slow-releasing H2S donor, GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino phosphinodithioate to study its lung protective potential in vitro and in vivo. RESULTS: In vitro, GYY4137 promoted capillary-like network formation, viability and reduced reactive oxygen species in hyperoxia-exposed human pulmonary artery endothelial cells. GYY4137 also protected mitochondrial function in alveolar epithelial cells. In vivo, GYY4137 preserved and restored normal alveolar growth in rat pups exposed from birth for 2 weeks to hyperoxia. GYY4137 also attenuated PHT as determined by improved pulmonary arterial acceleration time on echo-Doppler, pulmonary artery remodeling and right ventricular hypertrophy. GYY4137 also prevented pulmonary artery smooth muscle cell proliferation. CONCLUSIONS: H2S protects from impaired alveolar growth and PHT in experimental O2-induced lung injury. H2S warrants further investigation as a new therapeutic target for alveolar damage and PHT.

  20. Basal cell carcinoma of penis: case report.

    OpenAIRE

    Sulaiman, M Z; Polacarz, S V; Partington, P E

    1988-01-01

    Basal cell carcinoma of the penis is rare. A patient who presented with a penile and scrotal ulcer due to basal cell carcinoma is reported. Wide local excision and split skin grafting were performed to excise the lesion completely.

  1. The basal bodies of Chlamydomonas reinhardtii

    OpenAIRE

    Dutcher, Susan K.; O’Toole, Eileen T.

    2016-01-01

    The unicellular green alga, Chlamydomonas reinhardtii, is a biflagellated cell that can swim or glide. C. reinhardtii cells are amenable to genetic, biochemical, proteomic, and microscopic analysis of its basal bodies. The basal bodies contain triplet microtubules and a well-ordered transition zone. Both the mother and daughter basal bodies assemble flagella. Many of the proteins found in other basal body-containing organisms are present in the Chlamydomonas genome, and mutants in these genes...

  2. Pulmonary Metastasis of Basal Cell Carcinoma

    OpenAIRE

    Seo, Sang-Hee; Shim, Woo-Haing; SHIN, DONG-HOON; Kim, Yun-Seong; Sung, Hyun-Woo

    2011-01-01

    Although basal cell carcinoma is the most common skin cancer, it rarely metastasizes. Metastatic basal cell carcinoma may, therefore, initially elude diagnosis and management. We describe the case of a patient with a metastatic basal cell carcinoma present in the lungs. The differential diagnosis of suspected metastatic lesions should include metastases from a cutaneous basal cell carcinoma, in addition to those from more commonly metastasizing carcinomas, especially in patients with a histor...

  3. Mammary epithelial cell

    DEFF Research Database (Denmark)

    Kass, Laura; Erler, Janine Terra; Dembo, Micah;

    2007-01-01

    mammary gland. During breast development and cancer progression, the extracellular matrix is dynamically altered such that its composition, turnover, processing and orientation change dramatically. These modifications influence mammary epithelial cell shape, and modulate growth factor and hormonal...... organization, and promote cell invasion and survival. In this review, we discuss the role of stromal-epithelial interactions in normal and malignant mammary epithelial cell behavior. We specifically focus on how dynamic modulation of the biochemical and biophysical properties of the extracellular matrix elicit...

  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. 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...

  6. Basal cell carcinoma-treatment with cryosurgery

    Directory of Open Access Journals (Sweden)

    Kaur S

    2003-03-01

    Full Text Available Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  7. Basal cell carcinoma-treatment with cryosurgery

    OpenAIRE

    Kaur S; Thami G; Kanwar A

    2003-01-01

    Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  8. A possible etiology for the dilaceration and flexion of permanent tooth roots relative to bone remodeling gradients in alveolar bone

    Directory of Open Access Journals (Sweden)

    Richard G Standerwick

    2014-01-01

    Full Text Available Introduction: Trauma, altered tooth germ position and delayed tooth eruption have been hypothesized as possible causes of tooth root dilacerations and flexion, however these anatomical variations appear more commonly associated with posterior teeth and absence of traumatic history. The Hypothesis: Postulated is that tooth root dilaceration or flexion may be a result of tooth root sheath displacement due to gradients of bone remodeling present within alveolar bone. Evaluation of the Hypothesis: Alveolar bone displays bone remodeling gradients between coronal, apical and basal sections which affect bone plasticity. As a tooth is erupting or experiences delayed eruption, there are other relative dento-skeletal alterations occurring, such as the mesial drift of the dentition and transverse growth of the maxilla. It is plausible that during the physiologic and growth related alteration of the alveolar and basal bones, portions of developing tooth could be found within one or more of the plasticity zones, contributing to alteration of the root sheath and tooth root dilaceration.

  9. Effects of smoking on resorption of the residual alveolar ridges in complete denture wearers

    Directory of Open Access Journals (Sweden)

    Marković Dubravka

    2003-01-01

    Full Text Available Introduction Based on literature data it is obvious that there is a connection between smoking and periodontal diseases. Alveolar bone loss increases with smoking. Tobacco smoking affects the proportion of subgingival bacterial flora by influencing oxidoreduction potential of dental plaque and thus making conditions for development of anaerobic bacteria. According to some researchers, smoking affects the mineral component of bone tissue. Orthopantomograms show higher level of alveolar bone loss in smokers than in nonsmokers with the same level of oral hygiene. The aim of this study was to establish if smoking affects alveolar bone loss in complete denture wearers. Material and methods Our clinical investigation included 60 patients of both sexes (30 smokers and 30 nonsmokers all complete dentures wearers. All patients met study criteria: jaw relation and smokers who smoke over 20 cigarettes per day. All subjects were interviewed, and after that orthopantomograms were made. They were used to calculate the degree of alveolar bone loss. Results The examined subjects were approximately of the same age. Mean age of smokers was 59.9 and nonsmokers 61.8. It was established that differences regarding resorption in men were not significant. The degree of resorption in women smokers and women nonsmokers was different, but differences were not significant. Discussion It has been proven that the number of cigarettes smoked per day is very important. It is considered that the risk of oral epithelial dysplasia increases when smoking more than 20 cigarettes per day. Considering our results regarding resorption of edentulous alveolar ridge in smokers and nonsmokers, we concluded that there were no significant differences. There are opinions in literature that smoking is not an etiological factor in resorption, but there are some opinions that smoking is connected with the degree of resorption in periodontium. The analyses of resorptive changes in edentulous

  10. 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

  11. 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

  12. 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...

  13. Clear Cell Basal Cell Carcinoma

    OpenAIRE

    Bo Wang; Tracey Harbert; Jennifer Olivella; Daniel Olson; Sarma, Deba P; Stephanie Ortman

    2011-01-01

    Introduction. Clear cell basal cell carcinoma (BCC) is an uncommon and unusual variant of BCC, which is characterized by a variable component of clear cells. The pathogenesis of this histological variant and its clinical significance has not been clarified. Differentiation of this uncommon variant of BCC from other clear cell tumors is important for the treatment. Case Presentation. A 65-year-old male presented with a 0.9 cm dome-shaped lesion on his upper chest. A shave biopsy revealed a der...

  14. The basal ganglia in haemochromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Berg, D.; Hoggenmueller, U.; Becker, G. [Wuerzburg Univ. (Germany). Abt. fuer Neuroradiologie; Hofmann, E. [Division of Neuroradiology, University of Wuerzburg (Germany); Fischer, R. [Medical Division Heinz Kalk-Klinik, Bad Kissingen (Germany); Kraus, M.; Scheurlen, M. [Department of Medicine, University of Wuerzburg (Germany)

    2000-01-01

    Haemochromatosis is characterised by deposition of iron-containing pigment in various organs, but little is known about possible deposition in the brain and its clinical impact. We therefore investigated 14 patients with hereditary haemochromatosis with MRI, CT and transcranial ultrasound (TCS) and examined them neurologically. In six of the patients dense lesions were found within the lentiform nucleus on CT, all of whom displayed hyperechogenic lesions in the same area on TCS, as did one other patient. In these patients the relative signal intensities of the lentiform nucleus measured by MRI relaxometry were higher. No patient had clinical signs of basal ganglia disorders. (orig.)

  15. The basal ganglia in haemochromatosis

    International Nuclear Information System (INIS)

    Haemochromatosis is characterised by deposition of iron-containing pigment in various organs, but little is known about possible deposition in the brain and its clinical impact. We therefore investigated 14 patients with hereditary haemochromatosis with MRI, CT and transcranial ultrasound (TCS) and examined them neurologically. In six of the patients dense lesions were found within the lentiform nucleus on CT, all of whom displayed hyperechogenic lesions in the same area on TCS, as did one other patient. In these patients the relative signal intensities of the lentiform nucleus measured by MRI relaxometry were higher. No patient had clinical signs of basal ganglia disorders. (orig.)

  16. Basal Cell Adenoma of Palate, a Rare Occurrence with Review of Literature

    Directory of Open Access Journals (Sweden)

    Achla Bharti Yadav

    2015-09-01

    Full Text Available Basal cell adenoma is an uncommon benign epithelial neoplasm of salivary gland which derives its name from the basaloid appearance of tumor cells and accounting for 1-2 % of all salivary gland epithelial tumors. This tumor usually arises in the major salivary glands, with the parotid being the most frequent site of occurrence, followed by the upper lip; while it is very rare in the minor salivary glands. Microscopically, it is composed of isomorphic cells similar to basal cells with nuclear palisading. We report a case of BCA presenting as an asymptomatic swelling over the right side of palate of 55-year-old female patient. A follow-up of 1 year revealed no recurrence. This report emphasizes the rare site of occurrence of this tumor and briefly reviews the literature.

  17. Basal Cell Adenoma of Palate, a Rare Occurrence with Review of Literature.

    Science.gov (United States)

    Yadav, Achla Bharti; Narwal, Anjali; Devi, Anju; Kumar, Sanjay; Yadav, Sumit Kumar

    2015-09-01

    Basal cell adenoma is an uncommon benign epithelial neoplasm of salivary gland which derives its name from the basaloid appearance of tumor cells and accounting for 1-2 % of all salivary gland epithelial tumors. This tumor usually arises in the major salivary glands, with the parotid being the most frequent site of occurrence, followed by the upper lip; while it is very rare in the minor salivary glands. Microscopically, it is composed of isomorphic cells similar to basal cells with nuclear palisading. We report a case of BCA presenting as an asymptomatic swelling over the right side of palate of 55-year-old female patient. A follow-up of 1 year revealed no recurrence. This report emphasizes the rare site of occurrence of this tumor and briefly reviews the literature. PMID:26535412

  18. Protein kinase D is increased and activated in lung epithelial cells and macrophages in idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Huachen Gan

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a relentlessly progressive and usually fatal lung disease of unknown etiology for which no effective treatments currently exist. Hence, there is a profound need for the identification of novel drugable targets to develop more specific and efficacious therapeutic intervention in IPF. In this study, we performed immunohistochemical analyses to assess the cell type-specific expression and activation of protein kinase D (PKD family kinases in normal and IPF lung tissue sections. We also analyzed PKD activation and function in human lung epithelial cells. We found that PKD family kinases (PKD1, PKD2 and PKD3 were increased and activated in the hyperplastic and regenerative alveolar epithelial cells lining remodeled fibrotic alveolar septa and/or fibroblast foci in IPF lungs compared with normal controls. We also found that PKD family kinases were increased and activated in alveolar macrophages, bronchiolar epithelium, and honeycomb cysts in IPF lungs. Interestingly, PKD1 was highly expressed and activated in the cilia of IPF bronchiolar epithelial cells, while PKD2 and PKD3 were expressed in the cell cytoplasm and nuclei. In contrast, PKD family kinases were not apparently increased and activated in IPF fibroblasts or myofibroblasts. We lastly found that PKD was predominantly activated by poly-L-arginine, lysophosphatidic acid and thrombin in human lung epithelial cells and that PKD promoted epithelial barrier dysfunction. These findings suggest that PKD may participate in the pathogenesis of IPF and may be a novel target for therapeutic intervention in this disease.

  19. The basal bodies of Chlamydomonas reinhardtii.

    Science.gov (United States)

    Dutcher, Susan K; O'Toole, Eileen T

    2016-01-01

    The unicellular green alga, Chlamydomonas reinhardtii, is a biflagellated cell that can swim or glide. C. reinhardtii cells are amenable to genetic, biochemical, proteomic, and microscopic analysis of its basal bodies. The basal bodies contain triplet microtubules and a well-ordered transition zone. Both the mother and daughter basal bodies assemble flagella. Many of the proteins found in other basal body-containing organisms are present in the Chlamydomonas genome, and mutants in these genes affect the assembly of basal bodies. Electron microscopic analysis shows that basal body duplication is site-specific and this may be important for the proper duplication and spatial organization of these organelles. Chlamydomonas is an excellent model for the study of basal bodies as well as the transition zone. PMID:27252853

  20. Migraine attacks the Basal Ganglia

    Directory of Open Access Journals (Sweden)

    Bigal Marcelo

    2011-09-01

    Full Text Available Abstract Background With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month. The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF to a matched (gender, age, age of onset and type of medication group of patients whose migraine episodes progressed (HF. Results In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain. Conclusions Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.

  1. PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells.

    Science.gov (United States)

    Jeong, Jinseon; Kim, Young-Jun; Yoon, Sun Young; Kim, Yong-Jae; Kim, Joo Heon; Sohn, Ki-Young; Kim, Heung-Jae; Han, Yong-Hae; Chong, Saeho; Kim, Jae Wha

    2016-01-01

    Increased number of eosinophils in the circulation and sputum is associated with the severity of asthma. The respiratory epithelium produces chemokine (C-C motif) ligands (CCL) which recruits and activates eosinophils. A chemically synthesized monoacetyl-diglyceride, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) is a major constituent in the antlers of Sika deer (Cervus nippon Temminck) which has been used in oriental medicine. This study was aimed to investigate the molecular mechanism of PLAG effect on the alleviation of asthma phenotypes. A549, a human alveolar basal epithelial cell, and HaCaT, a human keratinocyte, were activated by the treatment of interleukin-4 (IL-4), and the expression of chemokines, known to be effective on the induction of eosinophil migration was analyzed by RT-PCR. The expression of IL-4 induced genes was modulated by the co-treatment of PLAG. Especially, CCL26 expression from the stimulated epithelial cells was significantly blocked by PLAG, which was confirmed by ELISA. The transcriptional activity of signal transducer and activator of transcription 6 (STAT6), activated by IL-4 mediated phosphorylation and nuclear translocation, was down-regulated by PLAG in a concentration-dependent manner. In ovalbumin-induced mouse model, the infiltration of immune cells into the respiratory tract was decreased by PLAG administration. Cytological analysis of the isolated bronchoalveolar lavage fluid (BALF) cells proved the infiltration of eosinophils was significantly reduced by PLAG. In addition, PLAG inhibited the migration of murine bone marrow-derived eosinophils, and human eosinophil cell line, EoL-1, which was induced by the addition of A549 culture medium. PMID:27010397

  2. Endothelial and Epithelial Cell Transition to a Mesenchymal Phenotype Was Delineated by Nestin Expression.

    Science.gov (United States)

    Chabot, Andréanne; Hertig, Vanessa; Boscher, Elena; Nguyen, Quang Trinh; Boivin, Benoît; Chebli, Jasmine; Bissonnette, Lyse; Villeneuve, Louis; Brochiero, Emmanuelle; Dupuis, Jocelyn; Calderone, Angelino

    2016-07-01

    Endothelial and epithelial cell transition to a mesenchymal phenotype was identified as cellular paradigms implicated in the appearance of fibroblasts and development of reactive fibrosis in interstitial lung disease. The intermediate filament protein nestin was highly expressed in fibrotic tissue, detected in fibroblasts and participated in proliferation and migration. The present study tested the hypothesis that the transition of endothelial and epithelial cells to a mesenchymal phenotype was delineated by nestin expression. Three weeks following hypobaric hypoxia, adult male Sprague-Dawley rats characterized by alveolar and perivascular lung fibrosis were associated with increased nestin protein and mRNA levels and marked appearance of nestin/collagen type I((+)) -fibroblasts. In the perivascular region of hypobaric hypoxic rats, displaced CD31((+)) -endothelial cells were detected, exhibited a mesenchymal phenotype and co-expressed nestin. Likewise, epithelial cells in the lungs of hypobaric hypoxic rats transitioned to a mesenchymal phenotype distinguished by the co-expression of E-cadherin and collagen. Following the removal of FBS from primary passage rat alveolar epithelial cells, TGF-β1 was detected in the media and a subpopulation acquired a mesenchymal phenotype characterized by E-cadherin downregulation and concomitant induction of collagen and nestin. Bone morphogenic protein-7 treatment of alveolar epithelial cells prevented E-cadherin downregulation, suppressed collagen induction but partially inhibited nestin expression. These data support the premise that the transition of endothelial and epithelial cells to a mesenchymal cell may have contributed in part to the appearance nestin/collagen type I((+)) -fibroblasts and the reactive fibrotic response in the lungs of hypobaric hypoxic rats. J. Cell. Physiol. 231: 1601-1610, 2016. © 2015 Wiley Periodicals, Inc. PMID:26574905

  3. 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

  4. Dynamic 99mTc-DTPA radioaerosol lung scanning for the evaluation of alveolar-capillary barrier permeability

    International Nuclear Information System (INIS)

    Pulmonary clearance of small droplet 99mTc-DTPA radioaerosol was studied in 100 patients (12 normal subjects, N; 10 asymptomatic healthy smoker, FA; 31 patients with interstitial lung diseases, IP; 47 patients with chronic obstructive lung disease, BPCO). The first seven minutes of clearance were described with the function At=Ao*exp(-K*t) and the time constant K was considered representative of the 99mTc-DTPA clearance rate and hence of the alveolar-capillary barrier permeability. Groups FA, IP and BPCO showed a significant (p99mTc-DTPA dynamic lung scanning is an easy, non-invasive method to assess derangements of alveolar-capillary barrier permeability secondary to epithelial damage; 2) permeability increase is a very early effect of cigarette smoke damafe to the epithelium; 3) other mechanisms of epithelial injury are present in diffuse lung disease; 4) while the clinical role of this new pathophysiological test is not yet clear, it is likely that it may become a very early marker of pulmonary epithelial damage in diffuse lung disease

  5. Defined conditions for the isolation and expansion of basal prostate progenitor cells of mouse and human origin.

    Science.gov (United States)

    Höfner, Thomas; Eisen, Christian; Klein, Corinna; Rigo-Watermeier, Teresa; Goeppinger, Stephan M; Jauch, Anna; Schoell, Brigitte; Vogel, Vanessa; Noll, Elisa; Weichert, Wilko; Baccelli, Irène; Schillert, Anja; Wagner, Steve; Pahernik, Sascha; Sprick, Martin R; Trumpp, Andreas

    2015-03-10

    Methods to isolate and culture primary prostate epithelial stem/progenitor cells (PESCs) have proven difficult and ineffective. Here, we present a method to grow and expand both murine and human basal PESCs long term in serum- and feeder-free conditions. The method enriches for adherent mouse basal PESCs with a Lin(-)SCA-1(+)CD49f(+)TROP2(high) phenotype. Progesterone and sodium selenite are additionally required for the growth of human Lin(-)CD49f(+)TROP2(high) PESCs. The gene-expression profiles of expanded basal PESCs show similarities to ESCs, and NF-kB function is critical for epithelial differentiation of sphere-cultured PESCs. When transplanted in combination with urogenital sinus mesenchyme, expanded mouse and human PESCs generate ectopic prostatic tubules, demonstrating their stem cell activity in vivo. This novel method will facilitate the molecular, genomic, and functional characterization of normal and pathologic prostate glands of mouse and human origin. PMID:25702639

  6. Microrheology of human lung epithelial cells measured by atomic force microscopy

    OpenAIRE

    Alcaraz, Jordi; Buscemi, Lara; Grabulosa, Mireia; Trepat, Xavier; Fabry, Ben; Farré, Ramon; Navajas, Daniel

    2003-01-01

    Lung epithelial cells are subjected to large cyclic forces from breathing. However, their response to dynamic stresses is poorly defined. We measured the complex shear modulus (G*(ω)) of human alveolar (A549) and bronchial (BEAS-2B) epithelial cells over three frequency decades (0.1–100 Hz) and at different loading forces (0.1–0.9 nN) with atomic force microscopy. G*(ω) was computed by correcting force-indentation oscillatory data for the tip-cell contact geometry and for the hydrodynamic vis...

  7. 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.

  8. Pulmonary alveolar proteinosis and aluminum dust exposure

    Energy Technology Data Exchange (ETDEWEB)

    Miller, R.R.; Churg, A.M.; Hutcheon, M.; Lom, S.

    1984-08-01

    A 44-yr-old male presented shortness of breath, diffuse X-ray infiltrates, and physiologic evidence of a restrictive lung disease. Biopsy revealed pulmonary alveolar proteinosis. The patient had worked for the previous 6 yr as an aluminum rail grinder in a very dusty environment. Analysis of his lung tissue revealed greater than 300 X 10(6) particles of aluminum/g dry lung; all of the particles appeared as spheres of less than 1 mu diameter. We believe that this case represents an example of pulmonary alveolar proteinosis induced by inhalation of aluminum particles; this finding confirms animal studies which suggest that proteinosis can be produced by very large doses of many types of finely divided mineral dust.

  9. 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

  10. Silver Nanoparticles in Alveolar Bone Surgery Devices

    Directory of Open Access Journals (Sweden)

    Stefano Sivolella

    2012-01-01

    Full Text Available Silver (Ag ions have well-known antimicrobial properties and have been applied as nanostrategies in many medical and surgical fields, including dentistry. The use of silver nanoparticles (Ag NPs may be an option for reducing bacterial adhesion to dental implant surfaces and preventing biofilm formation, containing the risk of peri-implant infections. Modifying the structure or surface of bone grafts and membranes with Ag NPs may also prevent the risk of contamination and infection that are common when alveolar bone augmentation techniques are used. On the other hand, Ag NPs have revealed some toxic effects on cells in vitro and in vivo in animal studies. In this setting, the aim of the present paper is to summarize the principle behind Ag NP-based devices and their clinical applications in alveolar bone and dental implant surgery.

  11. Bilateral stony lung: pulmonary alveolar microlithiasis.

    Science.gov (United States)

    Chandra, Subhash; Mohan, Anant; Guleria, Randeep; Das, Prasenjit; Sarkar, Chitra

    2009-01-01

    A 40-year-old male paddy field worker was referred for exertional shortness of breath and non-productive cough for 4 years. He had been treated for pulmonary tuberculosis twice. Chest radiograph showed extensive bilateral nodular opacities ("sandstorm-like") in the middle and lower lobe. Pulmonary function tests revealed a restrictive ventilatory defect. High resolution CT showed widespread nodular infiltration with "crazy paving" appearance and interrupted black pleura sign. This was confirmed as pulmonary alveolar microlithiasis (PAM) by trans-bronchial lung biopsy, which showed normal respiratory lining epithelium with dilated alveolar spaces containing many calcific bodies, some of which showed concentric calcification. The possibilities of silicosis (due to exposure to husk) and tuberculosis, both of which can mimic PAM clinically and radiologically, made this case a diagnostic challenge. PMID:21686505

  12. Alveolar ridge augmentation by osteoinduction in rats

    DEFF Research Database (Denmark)

    Pinholt, E M; Bang, G; Haanaes, H R

    1990-01-01

    The purpose of this study was to evaluate bone substitutes for alveolar ridge augmentation by osteoinduction. Allogenic, demineralized, and lyophilized dentin and bone was tested for osteoinductive properties in order to establish an experimental model for further studies. Implantations were...... performed subperiosteally on the premaxilla and heterotopically in the abdominal muscles of rats. Light microscopic evaluations revealed that all allogenic, demineralized, and lyophilized dentin and bone implants induced new bone formation. No inflammatory or foreign body reactions were observed....

  13. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment.

    Science.gov (United States)

    Degryse, Amber L; Tanjore, Harikrishna; Xu, Xiaochuan C; Polosukhin, Vasiliy V; Jones, Brittany R; Boomershine, Chad S; Ortiz, Camila; Sherrill, Taylor P; McMahon, Frank B; Gleaves, Linda A; Blackwell, Timothy S; Lawson, William E

    2011-06-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice that express β-galactosidase (β-gal) in cells of lung epithelial lineage. Mice were given intratracheal bleomycin (0.08 U), and the following parameters were assessed: AEC death by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay, inflammation by total and differential cell counts from bronchoalveolar lavage, fibrosis by scoring of trichrome-stained lung sections, and total lung collagen content. Mice with lung epithelial deficiency of TGFβR2 had improved AEC survival, despite greater lung inflammation, after bleomycin administration. At 3 wk after bleomycin administration, mice with epithelial TGFβR2 deficiency showed a significantly attenuated fibrotic response in the lungs, as determined by semiquantitatve scoring and total collagen content. The reduction in lung fibrosis in these mice was associated with a marked decrease in the lung fibroblast population, both total lung fibroblasts and epithelial-to-mesenchymal transition-derived (S100A4(+)/β-gal(+)) fibroblasts. Attenuation of TGFβ signaling in lung epithelium provides protection from bleomycin-induced fibrosis, indicating a critical role for the epithelium in transducing the profibrotic effects of this cytokine. PMID:21441353

  14. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment

    Science.gov (United States)

    Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; Boomershine, Chad S.; Ortiz, Camila; Sherrill, Taylor P.; McMahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.

    2011-01-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice that express β-galactosidase (β-gal) in cells of lung epithelial lineage. Mice were given intratracheal bleomycin (0.08 U), and the following parameters were assessed: AEC death by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay, inflammation by total and differential cell counts from bronchoalveolar lavage, fibrosis by scoring of trichrome-stained lung sections, and total lung collagen content. Mice with lung epithelial deficiency of TGFβR2 had improved AEC survival, despite greater lung inflammation, after bleomycin administration. At 3 wk after bleomycin administration, mice with epithelial TGFβR2 deficiency showed a significantly attenuated fibrotic response in the lungs, as determined by semiquantitatve scoring and total collagen content. The reduction in lung fibrosis in these mice was associated with a marked decrease in the lung fibroblast population, both total lung fibroblasts and epithelial-to-mesenchymal transition-derived (S100A4+/β-gal+) fibroblasts. Attenuation of TGFβ signaling in lung epithelium provides protection from bleomycin-induced fibrosis, indicating a critical role for the epithelium in transducing the profibrotic effects of this cytokine. PMID:21441353

  15. Myosin Id is required for planar cell polarity in ciliated tracheal and ependymal epithelial cells.

    Science.gov (United States)

    Hegan, Peter S; Ostertag, Eric; Geurts, Aron M; Mooseker, Mark S

    2015-10-01

    In wild type (WT) tracheal epithelial cells, ciliary basal bodies are oriented such that all cilia on the cell surface beat in the same upward direction. This precise alignment of basal bodies and, as a result, the ciliary axoneme, is termed rotational planar cell polarity (PCP). Rotational PCP in the multi-ciliated epithelial cells of the trachea is perturbed in rats lacking myosin Id (Myo1d). Myo1d is localized in the F-actin and basal body rich subapical cortex of the ciliated tracheal epithelial cell. Scanning and transmission electron microscopy of Myo1d knock out (KO) trachea revealed that the unidirectional bending pattern is disrupted. Instead, cilia splay out in a disordered, often radial pattern. Measurement of the alignment axis of the central pair axonemal microtubules was much more variable in the KO, another indicator that rotational PCP is perturbed. The asymmetric localization of the PCP core protein Vangl1 is lost. Both the velocity and linearity of cilia-driven movement of beads above the tracheal mucosal surface was impaired in the Myo1d KO. Multi-ciliated brain ependymal epithelial cells exhibit a second form of PCP termed translational PCP in which basal bodies and attached cilia are clustered at the anterior side of the cell. The precise asymmetric clustering of cilia is disrupted in the ependymal cells of the Myo1d KO rat. While basal body clustering is maintained, left-right positioning of the clusters is lost. PMID:26446290

  16. In situ methods for assessing alveolar mechanics.

    Science.gov (United States)

    Wu, You; Perlman, Carrie E

    2012-02-01

    Lung mechanics are an important determinant of physiological and pathophysiological lung function. Recent light microscopy studies of the intact lung have furthered the understanding of lung mechanics but used methodologies that may have introduced artifacts. To address this concern, we employed a short working distance water immersion objective to capture confocal images of a fluorescently labeled alveolar field on the costal surface of the isolated, perfused rat lung. Surface tension held a saline drop between the objective tip and the lung surface, such that the lung surface was unconstrained. For comparison, we also imaged with O-ring and coverslip; with O-ring, coverslip, and vacuum pressure; and without perfusion. Under each condition, we ventilated the lung and imaged the same region at the endpoints of ventilation. We found use of a coverslip caused a minimal enlargement of the alveolar field; additional use of vacuum pressure caused no further dimensional change; and absence of perfusion did not affect alveolar field dimension. Inflation-induced expansion was unaltered by methodology. In response to inflation, percent expansion was the same as recorded by all four alternative methods. PMID:22074721

  17. 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

  18. BASAL CELL CARCINOMA WITH ECCRINE DIFFERENTIATION: A RARE ENTITY

    Directory of Open Access Journals (Sweden)

    Divvya

    2014-05-01

    Full Text Available Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differentiation is practically very rare.

  19. BASAL CELL CARCINOMA WITH ECCRINE DIFFERENTIATION: A RARE ENTITY

    OpenAIRE

    Divvya; Rehana; Viswanathan; Krishnaswamy; Anvar Ali

    2014-01-01

    Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differen...

  20. Positron emission tomography and basal ganglia functions

    International Nuclear Information System (INIS)

    With the advent of positron emission tomography (PET), studies on the human brain function and pathophysiology of brain damage have been extremely progressed. It is well-known that the basal ganglia plays an important role as one of the central nervous system involved in exercise regulation. More recently, the potential involvement of the basal ganglia in psychological processes, such as cognitive function, has been pointed out, receiving much attention. In spite of such a lot of studies, however, basal ganglia function remains unclear. This paper describes the relationships between PET findings and basal ganglia function. PET findings are discussed in relation to brain energy metabolism and striatal dopamine function. Pathophysiology of the basal ganglia are described in terms of the following diseases: Parkinson's disease, Parkinson's syndrome, progressive supranuclear palsy, Huntington's disease, and dystonia. Physiological backgrounds of the basal ganglia for PET images are also referred to. (N.K.) 75 refs

  1. Changes in liquid clearance of alveolar epithelium after oleic acid-induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    陶军; 杨天德; 陈祥瑞; 黄河

    2004-01-01

    Objective:Impaired active fluid transport of alveolar epithelium may involve in the pathogenesis and resolution of alveolar edema. Thc objective of this study was to explore the changes in alveolar epithelial liquid clearance during lung edema following acute lung injury induced by oleic acid. Methods:Forty-eight Wistar rats were randomly divided into six groups, I.e. , injured, amiloride, ouabain, amiloride plus ouabain and terbutaline groups. Twenty- four hours after the induction of acute lung injury by intravenous oleic acid (0.25 ml/kg), 5% albumin solution with 1.5 μCi 125Ⅰ-labeled albumin (5 ml/kg) was delivered into both lungs via trachea. Alveolar liquid clearance (ALC), extravascular lung water ( EVLW ) content and arterial blood gases were measured one hour thereafter.Results: At 24 h after the infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia, with EVLW increased by 47.9% and ALC decreased by 49.2%. Addition of either 2 × 10-3 M amiloride or 5 × 10-4 M ouabain to the instillation further reduced ALC and increased EVLW. ALC increased by approximately 63.7% and EVLW decreased by 46.9% with improved hypoxemia in the Terbutaline (10-4 M) group, compared those in injured rats. A significant negative correlation was found between the increment of EVLW and the reduction of ALC. Onclusions:Active fluid transport of alveolar epithelium might play a role in the pathogenesis of lung edema in acute lung injury.

  2. On neurocomputational models of the basal ganglia

    OpenAIRE

    Ahmed Moustafa

    2009-01-01

    Over the past few decades, it became evident that the basal ganglia is involved in cognitive as well as motor processes, including motor control, conditioning, working memory, and sequence learning. Systems-levels models attempt to explain what kinds of computations are employed by the basal ganglia. It is argued that the basal ganglia integrates information from different structures, such as the prefrontal cortex and hippocampus, and decides on which motor response to execute. Learning such ...

  3. Functional Neuroanatomy of the Basal Ganglia

    OpenAIRE

    Lanciego, José L.; Luquin, Natasha; Obeso, José A.

    2012-01-01

    The “basal ganglia” refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amp...

  4. Striatal plasticity and basal ganglia circuit function

    OpenAIRE

    Kreitzer, Anatol C.; Malenka, Robert C.

    2008-01-01

    The dorsal striatum, which consists of the caudate and putamen, is the gateway to the basal ganglia. It receives convergent excitatory afferents from cortex and thalamus and forms the origin of the direct and indirect pathways—distinct basal ganglia circuits involved in motor control. It is also a major site of activity-dependent synaptic plasticity. Striatal plasticity alters the transfer of information throughout basal ganglia circuits and may represent a key neural substrate for adaptive m...

  5. Pathological basal ganglia activity in movement disorders

    OpenAIRE

    Wichmann, Thomas; Dostrovsky, Jonathan O

    2011-01-01

    Our understanding of the pathophysiology of movement disorders, and associated changes in basal ganglia activities has significantly changed in the course of the last few decades. This process began with the development of detailed anatomical models of the basal ganglia, followed by studies of basal ganglia activity patterns in animal models of common movement disorders and electrophysiological recordings in movement disorder patients undergoing functional neurosurgical procedures. These inve...

  6. Neglected Giant Scalp Basal Cell Carcinoma

    OpenAIRE

    Anne Kristine Larsen, MD; Waseem-Asim Ghulam El-Charnoubi, MD; Julie Gehl, MD, PhD; Christen Krag, MD, PhD

    2014-01-01

    Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstruct...

  7. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    OpenAIRE

    Yeliz Bilir; Erkan Gokce; Banu Ozturk; Faik Alev Deresoy; Ruken Yuksekkaya; Emel Yaman

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity...

  8. Evaluating alternative stem cell hypotheses for adultcorneal epithelial maintenance

    Institute of Scientific and Technical Information of China (English)

    John D West; Natalie J Dorà; Natalie J Dorà,

    2015-01-01

    In this review we evaluate evidence for three differenthypotheses that explain how the corneal epitheliumis maintained. The limbal epithelial stem cell (LESC)hypothesis is most widely accepted. This proposes thatstem cells in the basal layer of the limbal epithelium,at the periphery of the cornea, maintain themselvesand also produce transient (or transit) amplifying cells(TACs). TACs then move centripetally to the centre ofthe cornea in the basal layer of the corneal epitheliumand also replenish cells in the overlying suprabasallayers. The LESCs maintain the corneal epitheliumduring normal homeostasis and become more active torepair significant wounds. Second, the corneal epithelialstem cell (CESC) hypothesis postulates that, duringnormal homeostasis, stem cells distributed throughoutthe basal corneal epithelium, maintain the tissue.According to this hypothesis, LESCs are present in thelimbus but are only active during wound healing. We alsoconsider a third possibility, that the corneal epithelium ismaintained during normal homeostasis by proliferationof basal corneal epithelial cells without any input fromstem cells. After reviewing the published evidence,we conclude that the LESC and CESC hypotheses areconsistent with more of the evidence than the thirdhypothesis, so we do not consider this further. The LESCand CESC hypotheses each have difficulty accountingfor one main type of evidence so we evaluate the twokey lines of evidence that discriminate between them.Finally, we discuss how lineage-tracing experimentshave begun to resolve the debate in favour of theLESC hypothesis. Nevertheless, it also seems likely thatsome basal corneal epithelial cells can act as long-termprogenitors if limbal stem cell function is compromised.Thus, this aspect of the CESC hypothesis may have alasting impact on our understanding of corneal epithelialmaintenance, even if it is eventually shown that stemcells are restricted to the limbus as proposed by the

  9. Giant basal cell carcinoma Carcinoma basocelular gigante

    OpenAIRE

    Nilton Nasser; Nilton Nasser Filho; Bruno Trauczynski Neto; Lissandra Melati da Silva

    2012-01-01

    The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no s...

  10. Striatal plasticity and basal ganglia circuit function.

    Science.gov (United States)

    Kreitzer, Anatol C; Malenka, Robert C

    2008-11-26

    The dorsal striatum, which consists of the caudate and putamen, is the gateway to the basal ganglia. It receives convergent excitatory afferents from cortex and thalamus and forms the origin of the direct and indirect pathways, which are distinct basal ganglia circuits involved in motor control. It is also a major site of activity-dependent synaptic plasticity. Striatal plasticity alters the transfer of information throughout basal ganglia circuits and may represent a key neural substrate for adaptive motor control and procedural memory. Here, we review current understanding of synaptic plasticity in the striatum and its role in the physiology and pathophysiology of basal ganglia function. PMID:19038213

  11. Conditional deletion of Abca3 in alveolar type II cells alters surfactant homeostasis in newborn and adult mice

    OpenAIRE

    Besnard, Valérie; Matsuzaki, Yohei; Clark, Jean; Xu, Yan; Wert, Susan E.; Ikegami, Machiko; Stahlman, Mildred T.; Weaver, Timothy E.; Hunt, Alan N.; Postle, Anthony D.; Whitsett, Jeffrey A.

    2010-01-01

    ATP-binding cassette A3 (ABCA3) is a lipid transport protein required for synthesis and storage of pulmonary surfactant in type II cells in the alveoli. Abca3 was conditionally deleted in respiratory epithelial cells (Abca3Δ/Δ) in vivo. The majority of mice in which Abca3 was deleted in alveolar type II cells died shortly after birth from respiratory distress related to surfactant deficiency. Approximately 30% of the Abca3Δ/Δ mice survived after birth. Surviving Abca3Δ/Δ mice developed emphys...

  12. Alveolar pressure during high-frequency jet ventilation

    OpenAIRE

    Vught, Adrianus; Versprille, Adrian; Jansen, Jos

    1990-01-01

    textabstractWe studied the influence of ventilatory frequency (1-5 Hz), tidal volume, lung volume and body position on the end-expiratory alveolar-to-tracheal pressure difference during high-frequency jet ventilation (HFJV) in Yorkshire piglets. The animals were anesthetized and paralysed. Alveolar pressure was estimated with the clamp off method, which was performed by a computer controlled ventilator and which had been extensively tested on its feasibility. The alveolar-to-tracheal pressure...

  13. Pulmonary Surfactant Surface Tension Influences Alveolar Capillary Shape and Oxygenation

    OpenAIRE

    Ikegami, Machiko; Weaver, Timothy E.; Grant, Shawn N.; Whitsett, Jeffrey A.

    2009-01-01

    Alveolar capillaries are located in close proximity to the alveolar epithelium and beneath the surfactant film. We hypothesized that the shape of alveolar capillaries and accompanying oxygenation are influenced by surfactant surface tension in the alveolus. To prove our hypothesis, surfactant surface tension was regulated by conditional expression of surfactant protein (SP)-B in Sftpb−/− mice, thereby inhibiting surface tension–lowering properties of surfactant in vivo within 24 hours after d...

  14. Pulmonary Alveolar Proteinosis in Children: A case series

    OpenAIRE

    seyyed Ahmad Tabatabaei; abdollah karimi; Sedigheh Rafiee Tabatabaei; B Radpay; Farzaneh Jadali

    2010-01-01

    Pulmonary Alveolar Proteinosis(PAP) is a rare disease of unknown etiology, characterized by the accumulation of proteinoceous material in the alveoli that is rich in lipid and is positive on periodic acid-Schiff(PAS) stain. PAP is rare in children. Two forms are encountered in pediatric practice: congenital alveolar proteinosis (CAP) and a later–onset form that is generally less severe. Broncho-alveolar lavage is the key to diagnosis. Therapeutic lung lavages are the only effective treatment ...

  15. Pulmonary administration of 1,25-dihydroxyvitamin D3 to the lungs induces alveolar regeneration in a mouse model of chronic obstructive pulmonary disease.

    Science.gov (United States)

    Horiguchi, Michiko; Hirokawa, Mai; Abe, Kaori; Kumagai, Harumi; Yamashita, Chikamasa

    2016-07-10

    Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease with several causes, including smoking, and no curative therapeutic agent is available, particularly for destructive alveolar lesions. In this study, we investigated the differentiation-inducing effect on undifferentiated lung cells (Calu-6) and the alveolar regenerative effect of the active vitamin 1,25-dihydroxy vitamin D3 (VD3) with the ultimate goal of developing a novel curative drug for COPD. First, the differentiation-inducing effect of VD3 on Calu-6 cells was evaluated. Treatment with VD3 increased the proportions of type I alveolar epithelial (AT-I) and type II alveolar epithelial (AT-II) cells constituting alveoli in a concentration- and treatment time-dependent manner, demonstrating the potent differentiation-inducing activity of VD3 on Calu-6 cells. We thus administered VD3 topically to the mice lung using a previously developed intrapulmonary administration via self-inhalation method. To evaluate the alveolus-repairing effect of VD3, we administered VD3 intrapulmonarily to elastase-induced COPD model mice and computed the mean distance between the alveolar walls as an index of the extent of alveolar injury. Results showed significant decreases in the alveolar wall distance in groups of mice that received 0.01, 0.1, and 1μg/kg of intrapulmonary VD3, revealing excellent alveolus-regenerating effect of VD3. Furthermore, we evaluated the effect of VD3 on improving respiratory function using a respiratory function analyzer. Lung elasticity and respiratory competence [forced expiratory volume (FEV) 1 s %] are reduced in COPD, reflecting advanced emphysematous changes. In elastase-induced COPD model mice, although lung elasticity and respiratory competence were reduced, VD3 administered intrapulmonarily twice weekly for 2weeks recovered tissue elastance and forced expiratory volume in 0.05s to the forced vital capacity, which are indicators of lung elasticity and respiratory

  16. Characteristic aspects of alveolar proteinosis diagnosis Aspectos característicos do diagnóstico da proteinose alveolar

    OpenAIRE

    Thiago Prudente Bártholo; José Gustavo Pugliese; Luiz Carlos Aguiar Vaz; Cláudia Henrique da Costa; Rogério Rufino

    2012-01-01

    Alveolar proteinosis is an uncommon pulmonary disease characterized by an accumulation of surfactant in terminal airway and alveoli, thereby impairing gas exchange and engendering respiratory insufficiency in some cases. Three clinically and etiologically distinct forms of pulmonary alveolar proteinosis are recognized: congenital, secondary and idiopathic, the latter corresponding to 90% of the cases. In this case report we present a young male patient that was diagnosed with alveolar protein...

  17. The basal ganglia communicate with the cerebellum.

    Science.gov (United States)

    Bostan, Andreea C; Dum, Richard P; Strick, Peter L

    2010-05-01

    The basal ganglia and cerebellum are major subcortical structures that influence not only movement, but putatively also cognition and affect. Both structures receive input from and send output to the cerebral cortex. Thus, the basal ganglia and cerebellum form multisynaptic loops with the cerebral cortex. Basal ganglia and cerebellar loops have been assumed to be anatomically separate and to perform distinct functional operations. We investigated whether there is any direct route for basal ganglia output to influence cerebellar function that is independent of the cerebral cortex. We injected rabies virus (RV) into selected regions of the cerebellar cortex in cebus monkeys and used retrograde transneuronal transport of the virus to determine the origin of multisynaptic inputs to the injection sites. We found that the subthalamic nucleus of the basal ganglia has a substantial disynaptic projection to the cerebellar cortex. This pathway provides a means for both normal and abnormal signals from the basal ganglia to influence cerebellar function. We previously showed that the dentate nucleus of the cerebellum has a disynaptic projection to an input stage of basal ganglia processing, the striatum. Taken together these results provide the anatomical substrate for substantial two-way communication between the basal ganglia and cerebellum. Thus, the two subcortical structures may be linked together to form an integrated functional network. PMID:20404184

  18. Readiness in the Basal Reader: An Update.

    Science.gov (United States)

    Perkins, Pamela

    A study examined two 1989 basal reading series' (published by McGraw Hill and Holt) readiness/priming sequences in order to ascertain the theoretical bases of each and then compared the findings with those of an earlier study. All pages of the readiness/priming sequence student texts and workbooks of both basal reading series were analyzed using…

  19. Early recognition of basal cell naevus syndrome

    NARCIS (Netherlands)

    Veenstra-Knol, HE; Scheewe, JH; van der Vlist, GJ; van Doorn, ME; Ausems, MGEM

    2005-01-01

    The basal cell naevus syndrome is an autosomal dominant syndrome characterised by major manifestations such as basal cell carcinomas, jaw cysts, palmar or plantar pits, and intracranial calcifications. Early recognition is important in order to reduce morbidity due to cutaneous and cerebral malignan

  20. 3D-CT evaluation of secondary alveolar bone grafts in alveolar clefts

    Energy Technology Data Exchange (ETDEWEB)

    Naitoh, Hiroshi; Nishimura, Yoshihiko [Kyoto Univ. (Japan). Graduate School of Medicine; Yamawaki, Yoshiroh [Kyoto Katsura Hospital (Japan); Morimoto, Naoki [Kobe City General Hospital (Japan)

    2002-07-01

    From 1994 to 2000, we treated 116 patients with cleft alveolus by secondary alveolar bone grafts, and 48 of them were evaluated morphologically with 3D-CT. The frequency of successful bony bridging was significantly higher in the group whose grafts were completely enveloped (including the anterior alveolar ridge) with a mucoperiosteal flap. The frequency was also significantly higher in the group who underwent bone grafts at the age of 13 or less, and canine eruptions did not influence the ratio. Some cases showed such an improved growth pattern of grafted bone that the shape of the affected maxilla resembled that of the normal side, after long-term follow-up observations. The growth increment was remarkable in anterior maxillary height. Orthodontic management guides the canine or incisor into the reconstructed area of the previous cleft. We surmise that the new occlusal position puts pressure on the grafted bone and promotes further osteogenesis. These findings show that it is important to produce sufficient bony bridge to guide the canine or incisor, not the volume of grafted bone, in secondary alveolar bone grafts. Long-term follow-up observation, after more than 2-3 years, is also necessary to evaluate secondary alveolar bone grafts. (author)

  1. Interaction of the pathogenic mold Aspergillus fumigatus with lung epithelial cells

    Directory of Open Access Journals (Sweden)

    NirOsherov

    2012-09-01

    Full Text Available Aspergillus fumigatus is an opportunistic environmental mold that can cause severe allergic responses in atopic individuals and poses a life-threatening risk for severely immunocompromised patients. Infection is caused by inhalation of fungal spores (conidia into the lungs. The initial point of contact between the fungus and the host is a monolayer of lung epithelial cells. Understanding how these cells react to fungal contact is crucial to elucidating the pathobiology of Aspergillus-related disease states. The experimental systems, both in vitro and in vivo, used to study these interactions, are described. Distinction is made between bronchial and alveolar epithelial cells. The experimental findings suggest that lung epithelial cells are more than just “innocent bystanders” or a purely physical barrier against infection. They can be better described as an active extension of our innate immune system, operating as a surveillance mechanism that can specifically identify fungal spores and activate an offensive response to block infection. This response includes the internalization of adherent conidia and the release of cytokines, antimicrobial peptides and reactive oxygen species. In the case of allergy, lung epithelial cells can dampen an over-reactive immune response by releasing anti-inflammatory compounds such as kinurenine. This review summarizes our current knowledge regarding the interaction of A. fumigatus with lung epithelial cells. A better understanding of the interactions between A. fumigatus and lung epithelial cells has therapeutic implications, as stimulation or inhibition of the epithelial response may alter disease outcome.

  2. Nostril Base Augmentation Effect of Alveolar Bone Graft

    Directory of Open Access Journals (Sweden)

    Woojin Lee

    2013-09-01

    Full Text Available Background The aims of alveolar bone grafting are closure of the fistula, stabilization ofthe maxillary arch, support for the roots of the teeth adjacent to the cleft on each side.We observed nostril base augmentation in patients with alveolar clefts after alveolar bonegrafting. The purpose of this study was to evaluate the nostril base augmentation effect ofsecondary alveolar bone grafting in patients with unilateral alveolar cleft.Methods Records of 15 children with alveolar clefts who underwent secondary alveolar bonegrafting with autogenous iliac cancellous bone between March of 2011 and May of 2012 werereviewed. Preoperative and postoperative worm’s-eye view photographs and reconstructedthree-dimensional computed tomography (CT scans were used for photogrammetry. Thedepression of the nostril base and thickness of the philtrum on the cleft side were measuredin comparison to the normal side. The depression of the cleft side pyriform aperture wasmeasured in comparison to the normal side on reconstructed three-dimensional CT.Results Significant changes were seen in the nostril base (P=0.005, the philtrum length(P=0.013, and the angle (P=0.006. The CT measurements showed significant changes in thepyriform aperture (P<0.001 and the angle (P<0.001.Conclusions An alveolar bone graft not only fills the gap in the alveolar process but alsoaugments the nostril base after surgery. In this study, only an alveolar bone graft was performedto prevent bias from other procedures. Nostril base augmentation can be achieved byperforming alveolar bone grafts in children, in whom invasive methods are not advised.

  3. 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...

  4. Alveolar type II cells express a high-affinity receptor for pulmonary surfactant protein A

    International Nuclear Information System (INIS)

    Primary cultures of rat alveolar type II cells bind radiolabeled pulmonary surfactant protein A (SP-A) with high affinity. The binding of 125I-labeled SP-A is time- and temperature-dependent and is not accompanied by significant degradation. The binding process is saturable at low concentrations of SP-A, and unlabeled SP-A readily competes with labeled SP-A for cellular binding sites. Subsequent to binding, two pools of cell-associated 125I-labeled SP-A can be identified based upon sensitivity to trypsin at 0 degree C. It is likely that the trypsin-sensitive pool comprises 125I-labeled SP-A bound to the cell surface and the trypsin-insensitive pool comprises the internalized protein. Scatchard analysis of cell surface binding of SP-A at 0.1-10 μg/ml shows positive cooperativity at concentrations between 0.1 and 1 μg/ml. Hill plots give nH = 1.34 ± 0.08 with an apparent dissociation constant K'd = 1.02 ± 0.32 μg/ml. The binding of SP-A to type II cells shows an absolute requirement for Ca2+. The putative receptor for SP-A is unaffected by treatment of type II cells with a variety of proteases and N-Glycanase. Alveolar macrophages also exhibit high-affinity binding of SP-A, but rat lung fibroblasts and the alveolar epithelial cell line L2 exhibit only nonspecific binding

  5. Cytokeratin changes in cell culture systems of epithelial cells isolated from oral mucosa: a short review.

    Science.gov (United States)

    Gasparoni, Alberto; Squier, Christopher Alan; Fonzi, Luciano

    2005-01-01

    In the past three decades, many studies have analyzed ultrastructural and molecular markers of differentiation in squamous stratified epithelial tissues. In these tissues, epithelial cells migrating from the basal layer to the upper layers undergo drastic changes, which involve membrane-associated proteins, DNA synthesis, phenotypic aspects, lipid composition, and cytoskeletal components. Cytoskeletal components include a large and heterogeneous group, including intermediate filaments, components of the cornified envelope, and of the stratum corneum. When grown in mono- and multilayer cell cultures, epithelial cells isolated from the oral mucosa may reproduce many of the biochemical and morphological aspects of epithelial tissue in vivo. In the present paper, we examine phenotypic changes, development of suprabasal layer, and Involucrin expression occurring in differentiating oral epithelial cells, based on literature review and original data. PMID:16277157

  6. Arachidonate metabolism increases as rat alveolar type II cells differentiate in vitro

    International Nuclear Information System (INIS)

    Rat type II alveolar epithelial cells are known to undergo morphological and functional changes when maintained in culture for several days. Having previously demonstrated that these cells can deacylate free arachidonic acid (AA) and metabolize it to products of the cyclooxygenase pathway, the present study was undertaken to determine whether in vitro differentiation was accompanied by alterations in the availability and metabolism of AA. We assessed the constitutive and ionophore A23187-induced deacylation and metabolism of endogenous AA, as well as the metabolism of exogenously supplied AA, in primary cultures of rat type II cells at days 2, 4, and 7 after isolation. Levels of free endogenous AA were increased at day 4, whereas eicosanoid synthesis, predominantly prostaglandin E2 and prostacyclin, increased markedly only at day 7. A similar time course of augmentation of prostanoid release was seen in response to exogenous AA. Type II cells cultured on fibronectin, intended to hasten cell flattening and spreading, demonstrated accelerated increases in available free AA in response to A23187; cells cultured on basement membrane derived from Engelbreth-Holm-Swarm mouse sarcoma, known to maintain the type II phenotype, exhibited diminished levels of available free AA. From these findings, we conclude that alterations in arachidonate metabolism are linked to alterations in cellular phenotype. The potentiation of eicosanoid synthesis accompanying in vitro differentiation suggests a possible role for the alveolar epithelium in the modulation of inflammation and fibrosis in the distal lung

  7. Cultured fibroblasts from alveolar and gingival mucosae are biologically and biochemically different

    International Nuclear Information System (INIS)

    Tissues removed from the alveolar or gingival mucosa of 5 patients were separated into cell populations to assess the relative contributions each might make in wound healing intraorally. Growth curves and protein synthetic patterns of fibroblasts, free of epithelial cells, were obtained at pass 5. The morphologies of the two cell types were not grossly different. However, the AM cells (alveolar mucosa) had a generation time (gt) of 18.7 hrs. whereas the gt for KG cells (keratinized gingiva) was 49.6 hrs. Cells labeled in vitro with 35S-methionine had distinct patterns of protein synthesis. The AM cells had more of the 275, 220, 92, 80, 50 and 46 kd bands on the autoradiogram of a 7.5% PAGE slab gel than did the KG cells. The KG cells contained more of the 165, 84, 68, 60, 54, 51, 43, 36, and 32a kd bands. In a wound healing situation, the AM cells may be the first fibroblasts to rapidly divide to fill a defect, whereas the KG cells may require a longer time period to divide. This is the first report of biochemical and biological differences in these two fibroblast populations from cultured, human tissues

  8. 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

  9. A radiographic study of alveolar bone loss in Irish schoolchildren

    International Nuclear Information System (INIS)

    Bitewing radiographs were used to assess evidence of alveolar bone loss in 1492 children in the age range 7-12 years. According to the method used in this study, alveolar bone loss was shown to occur in 1.7% of the children, and maxillary teeth were affected twice as frequently as mandibular teeth. (Author)

  10. Perawatan Pulpa Gigi Sulung Disertai Abses Dento Alveolar

    OpenAIRE

    Nasution, Nurasiah Adita

    2008-01-01

    Abses dento alveolar adalah kumputan pus yang berada pada tulang alveolar sekitar apeks gigi akibat kematian pulpa. Matinya pulpa dapat disebabkan bakteri, trauma, iritasi mekanis, termis maupun kimiawi. Pengaruh bakteri merupakan penyebab kerusakan jaringan pulpa yang terbesar. Perluasan infeksi ke dalam jaringan periapikal dapat melalui foramen apikalke jaringan periodontal sehingga terjadi inflarnasi. Bila virulensi bakteri meningkat disertai rendahnya pertahanan tubuh penderita dapat ...

  11. Alveolar pressure during high-frequency jet ventilation

    NARCIS (Netherlands)

    A.J. van Vught (Adrianus); A. Versprille (Adrian); J.R.C. Jansen (Jos)

    1990-01-01

    textabstractWe studied the influence of ventilatory frequency (1-5 Hz), tidal volume, lung volume and body position on the end-expiratory alveolar-to-tracheal pressure difference during high-frequency jet ventilation (HFJV) in Yorkshire piglets. The animals were anesthetized and paralysed. Alveolar

  12. Alveolar ridge augmentation by osteoinductive materials in goats

    DEFF Research Database (Denmark)

    Pinholt, E M; Haanaes, H R; Roervik, M;

    1992-01-01

    The purpose of the present study was to determine whether alveolar ridge augmentation could be induced in goats. In 12 male goats allogenic, demineralized, and lyophilized dentin or bone was implanted subperiosteally on the buccal sides of the natural edentulous regions of the alveolar process...

  13. Tongue-Palate Contact of Perceptually Acceptable Alveolar Stops

    Science.gov (United States)

    Lee, Alice; Gibbon, Fiona E.; O'Donovan, Cliona

    2013-01-01

    Increased tongue-palate contact for perceptually acceptable alveolar stops has been observed in children with speech sound disorders (SSD). This is a retrospective study that further investigated this issue by using quantitative measures to compare the target alveolar stops /t/, /d/ and /n/ produced in words by nine children with SSD (20 tokens of…

  14. Unexplained alveolar hemorrhage associated with Ginkgo and ginseng use.

    Science.gov (United States)

    Carlile, Paul V

    2015-04-01

    The author presents a case of diffuse alveolar hemorrhage in a woman consuming Ginkgo biloba extract and ginseng. The patient had no illnesses or exposures that would predispose to diffuse alveolar hemorrhage, and an extensive evaluation revealed no etiology. The patient has had no further bleeding since discontinuing Ginkgo biloba extract and ginseng 1 year ago. PMID:25887018

  15. Anaesthetic management of bilateral alveolar proteinosis for bronchopulmonary lavage.

    OpenAIRE

    Dixit R; Chaudhari L; Mahashur A

    1998-01-01

    The most hazardous manifestation of pulmonary alveolar proteinosis is progressive hypoxia for which bronchopulmonary lavage (BPL) is the single most effective treatment. Unfortunately this procedure under general anesthesia itself increases the risk of hypoxia due to the need for one lung ventilation. It was therefore considered interesting to report the successful anaesthetic management of a patient with pulmonary alveolar proteinosis for Bronchopulmonary lavage.

  16. Trangenic misexpression of the differentiation-specific desmocollin isoform 1 in basal keratinocytes.

    Science.gov (United States)

    Henkler, F; Strom, M; Mathers, K; Cordingley, H; Sullivan, K; King, I

    2001-01-01

    Keratinocytes undergoing terminal differentiation are characterized by well-defined changes in protein expression, which contribute towards the transformation of cytoarchitecture and epithelial morphology. Characteristic patterns of desmosomal cadherins are tightly regulated and distinct isoforms are expressed during development and differentiation of epithelial tissues. Desmocollin-1 is strictly confined to suprabasal layers of epidermis, but it is absent in mitotically active, basal keratinocytes. This raises the question of whether basal desmocollin-1 could alter desmosomal functions and compromise keratinocyte proliferation, stratification, or early differentiation in skin. In this study, we misexpressed human desmocollin-1 in mouse epidermis, under control of the keratin-14 promoter. Transgenic animals were generated, which showed a specific expression of transgenic human desmocollin-1 in epidermal basal cells. High level transgenic expression, which was equal to or greater than endogenous protein levels, was observed in mice with multiple copy integration of the transgene. A punctate distribution of desmocollin-1 was demonstrated at the cell membrane by indirect immunofluorescence. Transgenic human desmocollin-1 colocalized with endogenous desmosomal marker proteins, indicating efficient incorporation into desmosomes. Transgenic mice did not display any obvious abnormalities, either in the histology of skin and hair follicles, or in the ultrastructure of desmosomes. These observations suggest that desmocollin-1 can function as a desmosomal cadherin both in basal and suprabasal cells. We propose that the differentiation-specific desmocollin isoforms desmocollin-1 and desmocollin-3 are functionally equivalent in basal epidermal cells and suggest that their changing expression patterns are markers, but not regulators, of the initial steps in keratinocyte differentiation. PMID:11168810

  17. 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.

  18. Inhibitory effects of French pine bark extract, Pycnogenol®, on alveolar bone resorption and on the osteoclast differentiation.

    Science.gov (United States)

    Sugimoto, Hideki; Watanabe, Kiyoko; Toyama, Toshizo; Takahashi, Shun-suke; Sugiyama, Shuta; Lee, Masaichi-Chang-il; Hamada, Nobushiro

    2015-02-01

    Pycnogenol(®) (PYC) is a standardized bark extract from French maritime pine (Pinus pinaster Aiton). We examined the inhibitory effects of PYC on alveolar bone resorption, which is a characteristic feature of periodontitis, induced by Porphyromonas gingivalis (P. gingivalis) and osteoclast differentiation. In rat periodontitis model, rats were divided into four groups: group A served as the non-infected control, group B was infected orally with P. gingivalis ATCC 33277, group C was administered PYC in the diet (0.025%: w/w), and group D was infected with P. gingivalis and administered PYC. Administration of PYC along with P. gingivalis infection significantly reduced alveolar bone resorption. Treatment of P. gingivalis with 1 µg/ml PYC reduced the number of viable bacterial cells. Addition of PYC to epithelial cells inhibited adhesion and invasion by P. gingivalis. The effect of PYC on osteoclast formation was confirmed by tartrate-resistant acid phosphatase staining. PYC treatment significantly inhibited osteoclast formation. Addition of PYC (1-100 µg/ml) to purified osteoclasts culture induced cell apoptosis. These results suggest that PYC may prevent alveolar bone resorption through its antibacterial activity against P. gingivalis and by suppressing osteoclastogenesis. Therefore, PYC may be useful as a therapeutic and preventative agent for bone diseases such as periodontitis. PMID:25336411

  19. Control of ductal vs. alveolar differentiation of mammary clonogens and susceptibility to radiation-induced mammary cancer

    International Nuclear Information System (INIS)

    We have developed an in vitro-in vivo transplantation assay for measuring the concentration of clonogenic epithelial cells in cell suspensions of rat mammary tissue. Rat mammary clonogens from organoid cultures are capable of the same degree of PLDR as clonogens in vivo. The growth and differentiation of mammary clonogens to alveolar colonies or ductal colonies is regulated as follows: a) in the presence of E2 and high prolactin (Prl), cortisol induces mammary clonogens to proliferate and differentiate to form alveolar colonies which secrete milk and begin losing clonogenic potential, b) in cortisol deficient rats, Prl and E2 synergistically stimulate non-secretory ductal colonies, formation of which retain clonogenic potential, c) E2 without progesterone stimulates alveolar colony formation in the presence of cortical and high Prl, d) progesterone inhibits mammary clonogen differentiation to milk-producing cells and induces ductogenesis in a dose responsive fashion in the presence of E2, cortisol and high Prl. High prolactin levels coupled with glucocorticoid deficiency increases the susceptibility to mammary carcinogenesis following low dose radiation exposure by increasing the number of total mammary clonogens which are the presumptive target cells and by stimulating their proliferation after exposure. (author)

  20. Treatment to pulmonary alveolar proteinosis with total bronchoalveolar lavage

    International Nuclear Information System (INIS)

    The pulmonary alveolar proteinosis is a rare disease with variable course and characterized by the accumulation of surfactant in the alveoli. By the treatment it was used the alveolar lavage with good results. We present the experience accumulated in the Las Americas clinic of Medellin city with the treatment of three patients with diagnosis of pulmonary alveolar proteinosis by alveolar lavage. We realized seven lavages, two of them bilateral and sequential. We didn't 't have important complications and in all cases we got good clinical and physiological results. Two patients had relapsed six and seven months after the first lavage and they needed a second lavage. We conclude that the pulmonary lavage is a secure and effective procedure in the treatment of the pulmonary alveolar proteinosis and the modality of bilateral sequential lavage is a good alternative and less expensive

  1. Contemporary Approaches in the Repair of Alveolar Clefts

    Directory of Open Access Journals (Sweden)

    Ufuk Tatli

    2014-08-01

    Full Text Available Cleft lip and palate is one of the most common craniofacial anomalies. The repair of the alveolar clefts is an important part of the treatment for patients with cleft lip and palate. The treatment concepts of alveolar bone grafting are still controversial. The corresponding controversial issues are; timing of alveolar bone grafting, graft materials, and timing of the orthodontic expansion. In the present article, aforementioned controversial issues and contemporary treatment modalities of the maxillary alveolar clefts were reviewed in the light of current literature. In conclusion, the most suitable time for alveolar bone grafting is mixed dentition period. Grafting procedure may be performed in the early or late phases of this period depending on some clinical features. Adjunct orthodontic expansion procedures should be performed before and/or after grafting depending on the patient's current features. [Archives Medical Review Journal 2014; 23(4.000: 563-574

  2. Thermodynamic Significance of Human Basal Metabolism

    Institute of Scientific and Technical Information of China (English)

    WangCuncheng

    1993-01-01

    The human basal state,a non-equilibrium steady state,is analysed in this paper in the light of the First and Second Laws of Thermodynamics whereby the thermodynamic significance of the basal metabolic rate and its distinction to the dissipation function and exergy loss are identified.The analysis demonstrates the correct expression of the effects of the blood flow on the heat balance in a human-body bio-heat model and the relationship between the basal metabolic rate and the blood perfusion.

  3. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie;

    2014-01-01

    SUMMARY: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local...... control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence...

  4. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD

    2014-03-01

    Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

  5. Defined Conditions for the Isolation and Expansion of Basal Prostate Progenitor Cells of Mouse and Human Origin

    OpenAIRE

    Thomas Höfner; Christian Eisen; Corinna Klein; Teresa Rigo-Watermeier; Stephan M. Goeppinger; Anna Jauch; Brigitte Schoell; Vanessa Vogel; Elisa Noll; Wilko Weichert; Irène Baccelli; Anja Schillert; Steve Wagner; Sascha Pahernik; Martin R. Sprick

    2015-01-01

    Summary Methods to isolate and culture primary prostate epithelial stem/progenitor cells (PESCs) have proven difficult and ineffective. Here, we present a method to grow and expand both murine and human basal PESCs long term in serum- and feeder-free conditions. The method enriches for adherent mouse basal PESCs with a Lin−SCA-1+CD49f+TROP2high phenotype. Progesterone and sodium selenite are additionally required for the growth of human Lin−CD49f+TROP2high PESCs. The gene-expression profiles ...

  6. Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool.

    Science.gov (United States)

    Mesa, Kailin R; Rompolas, Panteleimon; Zito, Giovanni; Myung, Peggy; Sun, Thomas Y; Brown, Samara; Gonzalez, David G; Blagoev, Krastan B; Haberman, Ann M; Greco, Valentina

    2015-06-01

    Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression). In contrast to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration. Here we show by intravital microscopy in live mice that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbours. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through transforming growth factor (TGF)-β activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool, as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviours and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis. PMID:25849774

  7. Niche induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool

    Science.gov (United States)

    Mesa, Kailin R.; Rompolas, Panteleimon; Zito, Giovanni; Myung, Peggy; Sun, Thomas Yang; Brown, Samara; Gonzalez, David; Blagoev, Krastan B.; Haberman, Ann M.; Greco, Valentina

    2015-01-01

    Summary Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression)1,2. Contrary to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration3. Here we show by intravital microscopy in live mice4–6 that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbors. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through TGFβ activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviors and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis. PMID:25849774

  8. 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

  9. Repair of tracheal epithelium by basal cells after chlorine-induced injury

    Directory of Open Access Journals (Sweden)

    Musah Sadiatu

    2012-11-01

    Full Text Available Abstract Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5 and keratin 14 (K14 for basal cells, Clara cell secretory protein (CCSP for Clara cells, and acetylated tubulin (AcTub for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10, but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion

  10. Translocation of PEGylated quantum dots across rat alveolar epithelial cell monolayers

    OpenAIRE

    Fazlollahi F; Sipos A; Kim YH; Hamm-Alvarez SF; Borok Z; Kim K-J; Crandall ED

    2011-01-01

    Farnoosh Fazlollahi1,8, Arnold Sipos1,2, Yong Ho Kim1,2, Sarah F Hamm-Alvarez6, Zea Borok1–3, Kwang-Jin Kim1,2,5–7, Edward D Crandall1,2,4,8 1Will Rogers Institute Pulmonary Research Center, 2Department of Medicine, 3Department of Biochemistry and Molecular Biology, 4Department of Pathology, 5Department of Physiology and Biophysics, 6Department of Pharmacology and Pharmaceutical Sciences, 7Department of Biomedical Engineering, 8Mork Family Department of Chemical Engineerin...

  11. Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

    Directory of Open Access Journals (Sweden)

    Boczkowski Jorge

    2009-04-01

    Full Text Available Abstract Background A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red and analyzed 2 time points (3 and 24 hours for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality was calculated. Results The use of MTT assay on THP-1 cells exposed for 24 hours appears to be the most sensitive experimental design to assess the cytotoxic effect of one nanoparticle. With this experimental set-up, Copper- and Zinc-based nanoparticles appear to be the most toxic. Titania, Alumina, Ceria and Zirconia-based nanoparticles show moderate toxicity, and no toxicity was observed for Tungsten Carbide. No correlation between cytotoxicity and equivalent spherical diameter or specific surface area was found. Conclusion Our study clearly highlights the difference of sensitivity between cell types and cytotoxicity assays that has to be carefully taken into account when assessing nanoparticles toxicity.

  12. Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

    OpenAIRE

    Boczkowski Jorge; Maillot-Marechal Emmanuelle; Dupont Aurélie; Rogerieux Françoise; Geys Jorina; Lanone Sophie; Lacroix Ghislaine; Hoet Peter

    2009-01-01

    Abstract Background A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red) and an...

  13. Oral epithelial dysplasia classification systems

    DEFF Research Database (Denmark)

    Warnakulasuriya, S; Reibel, J; Bouquot, J;

    2008-01-01

    report, we review the oral epithelial dysplasia classification systems. The three classification schemes [oral epithelial dysplasia scoring system, squamous intraepithelial neoplasia and Ljubljana classification] were presented and the Working Group recommended epithelial dysplasia grading for routine....... Several studies have shown great interexaminer and intraexaminer variability in the assessment of the presence or absence and the grade of oral epithelial dysplasia. The Working Group considered the two class classification (no/questionable/ mild - low risk; moderate or severe - implying high risk) and...

  14. The many faces of basal cell carcinoma

    OpenAIRE

    Jackson, Robert

    1982-01-01

    Basal cell carcinoma is the most easily cured carcinoma, but because of the many forms it can take, and because it grows so slowly, it can be misdiagnosed or neglected. The author discusses its more common forms and etiologic considerations.

  15. LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis.

    Science.gov (United States)

    Sartaj, Rachel; Chee, Ru-ik; Yang, Jing; Wan, Pengxia; Liu, Aihong; Guaiquil, Victor; Fuchs, Elaine; Rosenblatt, Mark I

    2016-02-01

    The cornea requires constant epithelial renewal to maintain clarity for appropriate vision. A subset of stem cells residing at the limbus is primarily responsible for maintaining corneal epithelium homeostasis. Trauma and disease may lead to stem cell deficiency and therapeutic targeting to replenish the stemness capacity has been stalled by the lack of reliable corneal epithelial stem cell markers. Here we identified the location of Lhx2 in mice (mLhx2) cornea and conjunctival tissue using an Lhx2eGFP reporter model and in human tissues (hLHX2). Lhx2 localized to the basal cells of central cornea, the conjunctiva and the entire limbal epithelium in humans and mice. To ascribe a functional role we generated Lhx2 conditional knockout (cKO) mice and the phenotypic effects in corneas were analyzed by slit lamp microscopy, in cell-based assays and in a model of corneal epithelium debridement. Immunodetection on corneal sections were used to visualize conjunctivalization, a sign of limbal barrier failure. Lhx2cKO mice produced reduced body hair and spontaneous epithelial defects in the cornea that included neovascularization, perforation with formation of scar tissue and opacification. Cell based assays showed that Lhx2cKO derived corneal epithelial cells have a significantly lower capacity to form colonies over time and delayed wound-healing recovery when compared to wildtype cells. Repeated corneal epithelial wounding resulted in decreased re-epithelialization and multiple cornea lesions in Lhx2cKO mice compared to normal recovery seen in wildtype mice. We conclude that Lhx2 is required for maintenance of the corneal epithelial cell compartment and the limbal barrier. PMID:26661907

  16. Probiotics promote endocytic allergen degradation in gut epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Song, Chun-Hua [Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou (China); Liu, Zhi-Qiang [Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou (China); Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada); Huang, Shelly [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada); Zheng, Peng-Yuan, E-mail: medp7123@126.com [Department of Gastroenterology, The Second Hospital, Zhengzhou University, Zhengzhou (China); Yang, Ping-Chang, E-mail: yangp@mcmaster.ca [Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON (Canada)

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer Knockdown of A20 compromised the epithelial barrier function. Black-Right-Pointing-Pointer The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Black-Right-Pointing-Pointer Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. Black-Right-Pointing-Pointer Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

  17. Probiotics promote endocytic allergen degradation in gut epithelial cells

    International Nuclear Information System (INIS)

    Highlights: ► Knockdown of A20 compromised the epithelial barrier function. ► The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. ► Antigens transported across A20-deficient HT-29 monolayers conserved antigenicity. ► Probiotic proteins increased the expression of A20 in HT-29 cells. -- Abstract: Background and aims: Epithelial barrier dysfunction plays a critical role in the pathogenesis of allergic diseases; the mechanism is to be further understood. The ubiquitin E3 ligase A20 (A20) plays a role in the endocytic protein degradation in the cells. This study aims to elucidate the role of A20 in the maintenance of gut epithelial barrier function. Methods: Gut epithelial cell line, HT-29 cell, was cultured into monolayers to evaluate the barrier function in transwells. RNA interference was employed to knock down the A20 gene in HT-29 cells to test the role of A20 in the maintenance of epithelial barrier function. Probiotic derived proteins were extracted from the culture supernatants using to enhance the expression of A20 in HT-29 cells. Results: The results showed that the knockdown of A20 compromised the epithelial barrier function in HT-29 monolayers, mainly increased the intracellular permeability. The fusion of endosome/lysosome was disturbed in the A20-deficient HT-29 cells. Allergens collected from the transwell basal chambers of A20-deficient HT-29 monolayers still conserved functional antigenicity. Treating with probiotic derived proteins increased the expression of A20 in HT-29 cells and promote the barrier function. Conclusion: A20 plays an important role in the maintenance of epithelial barrier function as shown by HT-29 monolayer. Probiotic derived protein increases the expression of A20 and promote the HT-29 monolayer barrier function.

  18. Vascular and epithelial damage in the lung of the mouse after X rays or neutrons

    International Nuclear Information System (INIS)

    The response of the lung was studied in CFLP mice after exposure of the whole thorax to X rays (250 kVp) or cyclotron neutrons (16 MeV deuterons on Be, mean energy 7.5 MeV). To measure blood volume and leakage of plasma proteins, 51Cr-labeled red blood cells and 125I-albumin were injected intravenously and 24 h later lungs were lavaged via the trachea. Radioactivities in lung tissue and lavage fluid were determined to estimate the accumulation of albumin in the interstitial and alveolar spaces indicating damage to blood vessels and alveolar epithelium respectively. Function of type II pneumonocytes was assessed by the amounts of surfactant (assayed as lipid phosphorous) released into the lavage fluid. During the first 6 weeks, lavage protein and surfactant were increased, the neutron relative biological effectiveness (RBE) being unity. During pneumonitis at 12-24 weeks, surfactant levels were normal, blood volume was decreased, and both interstitial and alveolar albumin were increased. Albumin levels then decreased. At late times after exposure (42-64 weeks) alveolar albumin returned to normal but interstitial albumin was still slightly elevated. Values of RBE for changes in blood volume and interstitial and alveolar albumin at 15 weeks and for changes in blood volume and interstitial albumin at 46 weeks were 1.4, comparable with that for animal survival at 180 days. The results indicate that surfactant production is not critical for animal survival. They suggest that changes in blood vessels and alveolar epithelium occur during acute pneumonitis; epithelial repair follows but some vascular damage may persist. The time course of the changes in albumin levels did not correlate with increases in collagen biosynthesis which have been observed as early as 1 month after exposure and persist for up to 1 year

  19. Methanol intoxication with bilateral basal ganglia infarct

    International Nuclear Information System (INIS)

    Methanol is a toxic agent that affects the central nervous system, especially the optic nerves and basal ganglia. Symmetrical hypodense lesions in the basal ganglia, which can be demonstrated by CT or MRI, is accepted as the most characteristic radiological feature of the disease. A case of a patient with bilateral putaminal hypodense infarcts due tomethanol intoxication is presented. Copyright (2001) Blackwell Science Pty Ltd

  20. Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

    OpenAIRE

    Lo Muzio Lorenzo

    2008-01-01

    Abstract Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic ...

  1. Somatotopic Organization of the Primate Basal Ganglia

    OpenAIRE

    Nambu, Atsushi

    2011-01-01

    Somatotopic organization is a fundamental and key concept to understand how the cortico-basal ganglia loop works. It is also indispensable knowledge to perform stereotaxic surgery for movement disorders. Here I would like to describe the somatotopic organization of the basal ganglia, which consist of the striatum, subthalamic nucleus, globus pallidus, and substantia nigra. Projections from motor cortical regions representing different body parts terminate in different regions of these nuclei....

  2. Somatotopic organization of the primate basal ganglia

    OpenAIRE

    Atsushi Nambu

    2011-01-01

    Somatotopic organization is a fundamental and key concept to understand how the cortico-basal ganglia loop works. It is also indispensable knowledge to perform stereotaxic surgery for movement disorders. Here I would like to describe the somatotopic organization of the basal ganglia, which consist of the striatum, subthalamic nucleus, globus pallidus and substantia nigra. Projections from motor cortical regions representing different body parts terminate in different regions of these nuclei. ...

  3. Coronaviruses in polarized epithelial cells

    NARCIS (Netherlands)

    Rossen, J W; Bekker, C P; Voorhout, W F; Horzinek, M C; Van der Ende, A; Strous, G J; Rottier, P J

    1995-01-01

    Coronaviruses have a marked tropism for epithelial cells. In this paper the interactions of the porcine transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV-A59) with epithelial cells are compared. Porcine (LLC-PK1) and murine (mTAL) epithelial cells were grown on permeable supp

  4. Genetics Home Reference: biotin-thiamine-responsive basal ganglia disease

    Science.gov (United States)

    ... Health Conditions biotin-thiamine-responsive basal ganglia disease biotin-thiamine-responsive basal ganglia disease Enable Javascript to ... boxes. Print All Open All Close All Description Biotin-thiamine-responsive basal ganglia disease is a disorder ...

  5. Recent advances in alveolar biology: Evolution and function of alveolar proteins☆

    OpenAIRE

    Orgeig, Sandra; Hiemstra, Pieter S.; Edwin J A Veldhuizen; Casals, Cristina; Clark, Howard W.; Haczku, Angela; Knudsen, Lars; Possmayer, Fred

    2010-01-01

    This review is focused on the evolution and function of alveolar proteins. The lung faces physical and environmental challenges, due to changing pressures/volumes and foreign pathogens, respectively. The pulmonary surfactant system is integral in protecting the lung from these challenges via two groups of surfactant proteins – the small molecular weight hydrophobic SPs, SP-B and -C, that regulate interfacial adsorption of the lipids, and the large hydrophilic SPs, SP-A and -D, which are surfa...

  6. Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway.

    Science.gov (United States)

    Moon, H-G; Cao, Y; Yang, J; Lee, J H; Choi, H S; Jin, Y

    2015-01-01

    Despite decades of research, the pathogenesis of acute respiratory distress syndrome (ARDS) remains poorly understood, thus impeding the development of effective treatment. Diffuse alveolar damage (DAD) and lung epithelial cell death are prominent features of ARDS. Lung epithelial cells are the first line of defense after inhaled stimuli, such as in the case of hyperoxia. We hypothesized that lung epithelial cells release 'messenger' or signaling molecules to adjacent or distant macrophages, thereby initiating or propagating inflammatory responses after noxious insult. We found that, after hyperoxia, a large amount of extracellular vesicles (EVs) were generated and released into bronchoalveolar lavage fluid (BALF). These hyperoxia-induced EVs were mainly derived from live lung epithelial cells as the result of hyperoxia-associated endoplasmic reticulum (ER) stress. These EVs were remarkably different from epithelial 'apoptotic bodies', as reflected by the significantly smaller size and differentially expressed protein markers. These EVs fall mainly in the size range of the exosomes and smaller microvesicles (MVs) (50-120 nm). The commonly featured protein markers of apoptotic bodies were not found in these EVs. Treating alveolar macrophages with hyperoxia-induced, epithelial cell-derived EVs led to an increased secretion of pro-inflammatory cytokines and macrophage inflammatory protein 2 (MIP-2). Robustly increased macrophage and neutrophil influx was found in the lung tissue of the mice intranasally treated with hyperoxia-induced EVs. It was determined that EV-encapsulated caspase-3 was largely responsible for the alveolar macrophage activation via the ROCK1 pathway. Caspase-3-deficient EVs induced less cytokine/MIP-2 release, reduced cell counts in BALF, less neutrophil infiltration and less inflammation in lung parenchyma, both in vitro and in vivo. Furthermore, the serum circulating EVs were increased and mainly derived from lung epithelial cells after

  7. Epidemiology of human alveolar echinococcosis in China.

    Science.gov (United States)

    Craig, Philip S

    2006-01-01

    Globally human alveolar echinococcosis (AE) is a rare zoonotic helminthic disease confined to the Northern Hemisphere as sporadic infections in rural populations, principally in some areas of North America, west-central Europe, the Near East, Siberia, Central Asia, Japan and China. In China the first human cases were reported from western regions in the 1960s, but most hospital records remain fragmented and inadequate. From the mid-1990s mass screening surveys using portable ultrasound scanners recorded higher prevalences (up to 6% by county) than in any other areas of the world with some village rates as high as 15%. Risk factors identified for AE cases included ethnicity, sex, age and occupation. The role of the dog in transmission of Echinococcus multilocularis to humans now appears to be significant and may be one of the most important risk factor, in combination with landscape/land-use features conducive to maintaining wildlife host populations. PMID:16338167

  8. CT diagnosis of pulmonary alveolar microlithiasis

    International Nuclear Information System (INIS)

    Purpose: To study the CT findings and evaluate the value of CT in the diagnosis of pulmonary alveolar microlithiasis (PAM). Methods: The CT findings of 9 cases of PAM proved by lung biopsy or clinical diagnosis were retrospectively analysed. Results: On conventional CT, pulmonary window revealed widespread intraalveolar calcifications of both lungs concentrating in the subpleural parenchyma of the middle and lower lobes. The CT value of microliths ranged from 200 to 400 HU, usually combined with pulmonary emphysema and interstitial fibrosis; Mediastinal window showed linear calcifications along pleura or scattered punctate calcifications in the concentrated area of microliths looking like flame or white line in the medial border. On HRCT, pulmonary window revealed diffuse ground-glass appearance, nodules of different sizes, more microliths along the bronchovesicular bundles and thickening of lobule septa. Conclusion: CT, especially HRCT, can better demonstrate pathological features and stage of PAM, playing an important role in diagnosis and differential diagnosis

  9. Computed tomographic appearances of pulmonary alveolar proteinosis

    International Nuclear Information System (INIS)

    We evaluated longitudinal changes in chest CT images in six cases (5 males and one female, age: 35-57 yr) of pulmonary alveolar proteinosis treated with bronchopulmonary lavage. Chest CT images on admission showed a mixed pattern of air-space consolidation and reticular or reticulonodular shadows in most cases and showed a peripheral clear zone in all cases. These shadows gradually diminished after bronchopulmonary lavage. Some cases revealed early improvement in the hilar zone while others had equal improvement in all lung lesions. In one case, consolidation was changed into reticular shadows by treatment. Previous reports have indicated that 'interstitial shadows which disappeared with lavage' reflect edematous thickening of interlobular septa. However, our longitudinal evaluation suggests that interstitial shadows on CT images may reflect not only real interstitial infiltration but also inhomogeneous distribution of intralobular deposits. (author)

  10. Computed tomographic appearances of pulmonary alveolar proteinosis

    Energy Technology Data Exchange (ETDEWEB)

    Takiguchi, Yasuo; Uchiyama, Takashi; Nagao, Keiichi; Kuriyama, Takayuki (Chiba Univ. (Japan). School of Medicine); Fujita, Akira; Hashizume, Ikko

    1994-03-01

    We evaluated longitudinal changes in chest CT images in six cases (5 males and one female, age: 35-57 yr) of pulmonary alveolar proteinosis treated with bronchopulmonary lavage. Chest CT images on admission showed a mixed pattern of air-space consolidation and reticular or reticulonodular shadows in most cases and showed a peripheral clear zone in all cases. These shadows gradually diminished after bronchopulmonary lavage. Some cases revealed early improvement in the hilar zone while others had equal improvement in all lung lesions. In one case, consolidation was changed into reticular shadows by treatment. Previous reports have indicated that 'interstitial shadows which disappeared with lavage' reflect edematous thickening of interlobular septa. However, our longitudinal evaluation suggests that interstitial shadows on CT images may reflect not only real interstitial infiltration but also inhomogeneous distribution of intralobular deposits. (author).

  11. KL-6 concentration in pulmonary epithelial lining fluid is a useful prognostic indicator in patients with acute respiratory distress syndrome

    OpenAIRE

    Kondo, Tomohiro; Hattori, Noboru; Ishikawa, Nobuhisa; MURAI, HIROSHI; Haruta, Yoshinori; Hirohashi, Nobuyuki; Tanigawa, Koichi; Kohno, Nobuoki

    2011-01-01

    Background: KL-6 is a mucin-like glycoprotein expressed on the surface of alveolar type II cells. Elevated concentrations of KL-6 in serum and epithelial lining fluid (ELF) in patients with acute respiratory distress syndrome (ARDS) have been previously reported; however, kinetics and prognostic significance of KL-6 have not been extensively studied. This study was conducted to clarify these points in ARDS patients.Methods: Thirty-two patients with ARDS who received mechanical ventilation und...

  12. KL-6 concentration in pulmonary epithelial lining fluid is a useful prognostic indicator in patients with acute respiratory distress syndrome

    OpenAIRE

    Tanigawa Koichi; Hirohashi Nobuyuki; Haruta Yoshinori; Murai Hiroshi; Ishikawa Nobuhisa; Hattori Noboru; Kondo Tomohiro; Kohno Nobuoki

    2011-01-01

    Abstract Background KL-6 is a mucin-like glycoprotein expressed on the surface of alveolar type II cells. Elevated concentrations of KL-6 in serum and epithelial lining fluid (ELF) in patients with acute respiratory distress syndrome (ARDS) have been previously reported; however, kinetics and prognostic significance of KL-6 have not been extensively studied. This study was conducted to clarify these points in ARDS patients. Methods Thirty-two patients with ARDS who received mechanical ventila...

  13. Phylogenetic differences of mammalian basal metabolic rate are not explained by mitochondrial basal proton leak

    OpenAIRE

    Polymeropoulos, E. T.; Heldmaier, G; Frappell, P. B.; McAllan, B. M.; Withers, K. W.; M. Klingenspor; White, C.R.; Jastroch, M.

    2011-01-01

    Metabolic rates of mammals presumably increased during the evolution of endothermy, but molecular and cellular mechanisms underlying basal metabolic rate (BMR) are still not understood. It has been established that mitochondrial basal proton leak contributes significantly to BMR. Comparative studies among a diversity of eutherian mammals showed that BMR correlates with body mass and proton leak. Here, we studied BMR and mitochondrial basal proton leak in liver of various marsupial species. Su...

  14. Haemophilia, AIDS and lung epithelial permeability

    International Nuclear Information System (INIS)

    Lung 99mTc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung 99mTc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of 99mTc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au)

  15. Haemophilia, AIDS and lung epithelial permeability

    Energy Technology Data Exchange (ETDEWEB)

    O' Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G. (Haemophilia Centre and Coagulation Research Unit, Department of Nuclear Medicine, Rayne Institute, St. Thomas' Hospital, London (United Kingdom))

    1990-01-01

    Lung {sup 99m}Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung {sup 99m}Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of {sup 99m}Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au).

  16. An Epithelial Serine Protease, AgESP, Is Required for Plasmodium Invasion in the Mosquito Anopheles gambiae

    OpenAIRE

    Rodrigues, Janneth; Oliveira, Giselle A.; Kotsyfakis, Michalis; Dixit, Rajnikant; Molina-Cruz, Alvaro; Jochim, Ryan; Barillas-Mury, Carolina

    2012-01-01

    Background Plasmodium parasites need to cross the midgut and salivary gland epithelia to complete their life cycle in the mosquito. However, our understanding of the molecular mechanism and the mosquito genes that participate in this process is still very limited. Methodology/Principal Findings We identified an Anopheles gambiae epithelial serine protease (AgESP) that is constitutively expressed in the submicrovillar region of mosquito midgut epithelial cells and in the basal side of the sali...

  17. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Flemban, Arwa [Department of Biological, Biomedical and Analytical Sciences, Faculty of Health and Applied Sciences, University of West of England, Bristol BS16 1QY (United Kingdom); Department of Pathology, Faculty of Medicine, Umm Al-Qura University, Makkah 24382 (Saudi Arabia); Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical and Analytical Sciences, Faculty of Health and Applied Sciences, University of West of England, Bristol BS16 1QY (United Kingdom)

    2015-09-16

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh) pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT.

  18. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    International Nuclear Information System (INIS)

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh) pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT

  19. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    Directory of Open Access Journals (Sweden)

    Arwa Flemban

    2015-09-01

    Full Text Available The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT.

  20. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis.

    Science.gov (United States)

    Flemban, Arwa; Qualtrough, David

    2015-01-01

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh) pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT. PMID:26389956

  1. Crazy paving radiography finding in asymptomatic pulmonary alveolar proteinosis.

    Science.gov (United States)

    Choi, Young Rak; Chang, You-Jin; Kim, Si Wook; Choe, Kang Hyeon; Lee, Ki Man; An, Jin-Young

    2015-06-01

    Pulmonary alveolar proteinosis is a rare disorder characterized by alveolar accumulation of surfactant phospholipids and protein components. The symptoms and prognosis are extremely variable. Bronchoalveolar lavage fluid and/or transbronchial lung biopsy are useful for diagnosis; surgical lung biopsy is often unnecessary but useful in the focal involvement. We report a case of pulmonary alveolar proteinosis in a 50-year-old woman, confirmed by a video-assisted thoracoscopic surgery biopsy from the initial focal involvement, with normal bronchoalveolar lavage and transbronchial lung biopsy findings. PMID:25182335

  2. Upper Alveolar Ridge in Edentulous Patients and Caldwell Luc Surgery

    OpenAIRE

    Ashok Murthy, V.; Mahendra Kumar, R.

    2012-01-01

    The aim of this study is to understand the upper alveolar ridge changes and its impact on Caldwell Luc surgery, in a patient papulation from a Medical College Hospital. We undertook a study to measure the thickness of upper alveolar ridge in edentulous and edentulous patients, to know the difference between the two and its effects on Caldwell Luc surgery. The finding of the study led us to conclude that the upper alveolar ridge is quite thin in edentulous patients and requires care while scra...

  3. Lidocaine, dexmedetomidine and their combination reduce isoflurane minimum alveolar concentration in dogs.

    Directory of Open Access Journals (Sweden)

    Carlos M Acevedo-Arcique

    Full Text Available The effects of intravenous (i.v. lidocaine, dexmedetomidine and their combination delivered as a bolus followed by a constant rate infusion (CRI on the minimum alveolar concentration of isoflurane (MACISO in dogs were evaluated. Seven healthy adult dogs were included. Anaesthesia was induced with propofol and maintained with isoflurane. For each dog, baseline MAC (MACISO/BASAL was determined after a 90-minute equilibration period. Thereafter, each dog received one of the following treatments (loading dose, CRI: lidocaine 2 mg kg(-1, 100 µg kg(-1 minute(-1; dexmedetomidine 2 µg kg(-1, 2 µg kg(-1 hour(-1; or their combination. MAC was then determined again after 45- minutes of treatment by CRI. At the doses administered, lidocaine, dexmedetomidine and their combination significantly reduced MACISO by 27.3% (range: 12.5-39.2%, 43.4% (33.3-53.3% and 60.9% (46.1-78.1%, respectively, when compared to MACISO/BASAL. The combination resulted in a greater MACISO reduction than the two drugs alone. Their use, at the doses studied, provides a clinically important reduction in the concentration of ISO during anaesthesia in dogs.

  4. Pulmonary surfactant and its components inhibit secretion of phosphatidylcholine from cultured rat alveolar type II cells

    International Nuclear Information System (INIS)

    Pulmonary surfactant is synthesized and secreted by alveolar type II cells. Radioactive phosphatidylcholine has been used as a marker for surfactant secretion. The authors report findings that suggest that surfactant inhibits secretion of 3H-labeled phosphatidylcholine by cultured rat type II cells. The lipid components and the surfactant protein group of M/sub r/ 26,000-36,000 (SP 26-36) inhibit secretion to different extents. Surfactant lipids do not completely inhibit release; in concentrations of 100 μg/ml, lipids inhibit stimulated secretion by 40%. SP 26-36 inhibits release with an EC50 of 0.1 μg/ml. At concentrations of 1.0 μg/ml, SP 26-36 inhibits basal secretion and reduces to basal levels secretion stimulated by terbutaline, phorbol 12-myristate 13-acetate, and the ionophore A23187. The inhibitory effect of SP 26-36 can be blocked by washing type II cells after adding SP 26-36, by heating the proteins to 1000C for 10 min, by adding antiserum specific to SP 26-36, or by incubating cells in the presence of 0.2 mM EGTA. SP 26-36 isolated from canine and human sources also inhibits phosphatidylcholine release from rat type II cells. Neither type I collagen nor serum apolipoprotein A-1 inhibits secretion. These findings are compatible with the hypothesis that surfactant secretion is under feedback regulatory control

  5. Evaluation of the ‘Hedgehog’ signaling pathways in squamous and basal cell carcinomas of the eyelids and conjunctiva

    OpenAIRE

    Celebi, Ali Riza Cenk; Kiratli, Hayyam; SOYLEMEZOGLU, FIGEN

    2016-01-01

    The purpose of the present study was to assess the role of hedgehog signaling pathway in the carcinogenesis of eyelid skin and conjunctival epithelial malignant tumors. The study was conducted on specimens from 41 patients with cutaneous eyelid basal cell carcinoma, 22 with bulbar conjunctival squamous cell carcinoma, 12 with bulbar conjunctival intraepithelial neoplasia. Major molecules of Hedgehog signaling pathway (Sonic Hedgehog [Shh] and Patched-1 [Ptch-1] and Glioma-associated oncogene ...

  6. Basal cell adenoma of the parotid gland: Cytological diagnosis of an uncommon tumor.

    Science.gov (United States)

    Bhat, Amoolya; Rao, Madhuri; Geethamani, V; Shetty, Archana C

    2015-01-01

    Basal cell adenoma (BCA) is a rare benign epithelial tumor of the salivary gland, displaying monomorphic basaloid cells without a myxochondroid component, representing 1-3% of all salivary gland neoplasms seen predominantly in women over 50 years of age. It is uncommon in young adults. Cytodiagnosis of basaloid tumors chiefly basal cell adenoma of the salivary gland, is extremely challenging. The cytological differential diagnoses range from benign to malignant, neoplastic to non- neoplastic lesions. Histopathological examination is a must for definitive diagnosis, as these entities differ in prognosis and therapeutic aspects. We present a 22-years-old male with this uncommon diagnosis with a discussion on the role of cytological diagnosis. Fine needle aspiration cytology is a simple, minimally invasive method for the preoperative diagnosis of various types of neoplastic and non-neoplastic lesions. The knowledge of its pitfalls and limitations contributes to a more effective approach to treatment. PMID:26097318

  7. Basal cell adenoma of the parotid gland: Cytological diagnosis of an uncommon tumor

    Directory of Open Access Journals (Sweden)

    Amoolya Bhat

    2015-01-01

    Full Text Available Basal cell adenoma (BCA is a rare benign epithelial tumor of the salivary gland, displaying monomorphic basaloid cells without a myxochondroid component, representing 1-3% of all salivary gland neoplasms seen predominantly in women over 50 years of age. It is uncommon in young adults. Cytodiagnosis of basaloid tumors chiefly basal cell adenoma of the salivary gland, is extremely challenging. The cytological differential diagnoses range from benign to malignant, neoplastic to non- neoplastic lesions. Histopathological examination is a must for definitive diagnosis, as these entities differ in prognosis and therapeutic aspects. We present a 22-years-old male with this uncommon diagnosis with a discussion on the role of cytological diagnosis. Fine needle aspiration cytology is a simple, minimally invasive method for the preoperative diagnosis of various types of neoplastic and non-neoplastic lesions. The knowledge of its pitfalls and limitations contributes to a more effective approach to treatment.

  8. Regulated Mucin Secretion from Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    BurtonFDickey

    2013-09-01

    Full Text Available Secretory epithelial cells of the proximal airways synthesize and secrete gel-forming polymeric mucins. The secreted mucins adsorb water to form mucus that is propelled by neighboring ciliated cells, providing a mobile barrier which removes inhaled particles and pathogens from the lungs. Several features of the intracellular trafficking of mucins make the airway secretory cell an interesting comparator for the cell biology of regulated exocytosis. Polymeric mucins are exceedingly large molecules (up to 3x10^6 D per monomer whose folding and initial polymerization in the ER requires the protein disulfide isomerase Agr2. In the Golgi, mucins further polymerize to form chains and possibly branched networks comprising more than 20 monomers. The large size of mucin polymers imposes constraints on their packaging into transport vesicles along the secretory pathway. Sugar side chains account for >70% of the mass of mucins, and their attachment to the protein core by O-glycosylation occurs in the Golgi. Mature polymeric mucins are stored in large secretory granules ~1 um in diameter. These are translocated to the apical membrane to be positioned for exocytosis by cooperative interactions among MARCKS, cysteine string protein (CSP, HSP70 and the cytoskeleton. Mucin granules undergo exocytic fusion with the plasma membrane at a low basal rate and a high stimulated rate. Both rates are mediated by a regulated exocytic mechanism as indicated by phenotypes in both basal and stimulated secretion in mice lacking Munc13-2, a sensor of the second messengers calcium and diacylglycerol (DAG. Basal secretion is induced by low levels of activation of P2Y2 purinergic and A3 adenosine receptors by extracellular ATP released in paracrine fashion and its metabolite adenosine. Stimulated secretion is induced by high levels of the same ligands, and possibly by inflammatory mediators as well. Activated receptors are coupled to phospholipase C by Gq, resulting in the

  9. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage.

    Directory of Open Access Journals (Sweden)

    Nisha M Badders

    Full Text Available BACKGROUND: Ectopic Wnt signaling induces increased stem/progenitor cell activity in the mouse mammary gland, followed by tumor development. The Wnt signaling receptors, Lrp5/6, are uniquely required for canonical Wnt activity. Previous data has shown that the absence of Lrp5 confers resistance to Wnt1-induced tumor development. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that all basal mammary cells express Lrp5, and co-express Lrp6 in a similar fashion. Though Wnt dependent transcription of key target genes is relatively unchanged in mammary epithelial cell cultures, the absence of Lrp5 specifically depletes adult regenerative stem cell activity (to less than 1%. Stem cell activity can be enriched by >200 fold (over 80% of activity, based on high Lrp5 expression alone. Though Lrp5 null glands have apparent normal function, the basal lineage is relatively reduced (from 42% basal/total epithelial cells to 22% and Lrp5-/- mammary epithelial cells show enhanced expression of senescence-associated markers in vitro, as measured by expression of p16(Ink4a and TA-p63. CONCLUSIONS/SIGNIFICANCE: This is the first single biomarker that has been demonstrated to be functionally involved in stem cell maintenance. Together, these results demonstrate that Wnt signaling through Lrp5 is an important component of normal mammary stem cell function.

  10. CFTR is required for maximal transepithelial liquid transport in pig alveolar epithelia

    OpenAIRE

    Li, Xiaopeng; Comellas, Alejandro P.; Karp, Philip H.; Ernst, Sarah E.; Moninger, Thomas O.; Gansemer, Nicholas D.; Taft, Peter J.; Pezzulo, Alejandro A; Michael V Rector; Rossen, Nathan; Stoltz, David A.; McCray, Paul B.; Welsh, Michael J.; Zabner, Joseph

    2012-01-01

    A balance between alveolar liquid absorption and secretion is critical for maintaining optimal alveolar subphase liquid height and facilitating gas exchange in the alveolar space. However, the role of cystic fibrosis transmembrane regulator protein (CFTR) in this homeostatic process has remained elusive. Using a newly developed porcine model of cystic fibrosis, in which CFTR is absent, we investigated ion transport properties and alveolar liquid transport in isolated type II alveolar epitheli...

  11. 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...

  12. Role of alveolar type II cells and of surfactant-associated protein C mRNA levels in the pathogenesis of respiratory distress in mink kits infected with Aleutian mink disease parvovirus.

    OpenAIRE

    Viuff, B; Aasted, B; Alexandersen, S.

    1994-01-01

    Neonatal mink kits infected with Aleutian mink disease parvovirus (ADV) develop an acute interstitial pneumonia with clinical symptoms and pathological lesions that resemble those seen in preterm human infants with respiratory distress syndrome and in human adults with adult respiratory distress syndrome. We have previously suggested that ADV replicates in the alveolar type II epithelial cells of the lung. By using double in situ hybridization, with the simultaneous use of a probe to detect A...

  13. Localized basal meningeal enhancement in tuberculous meningitis

    International Nuclear Information System (INIS)

    Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

  14. Localized basal meningeal enhancement in tuberculous meningitis

    Energy Technology Data Exchange (ETDEWEB)

    Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du [University of Stellenbosch, Department of Radiology, Tygerberg Hospital, P.O. BOX 19063, Tygerberg (South Africa)

    2006-11-15

    Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

  15. Somatotopic organization of the primate basal ganglia

    Directory of Open Access Journals (Sweden)

    Atsushi Nambu

    2011-04-01

    Full Text Available Somatotopic organization is a fundamental and key concept to understand how the cortico-basal ganglia loop works. It is also indispensable knowledge to perform stereotaxic surgery for movement disorders. Here I would like to describe the somatotopic organization of the basal ganglia, which consist of the striatum, subthalamic nucleus, globus pallidus and substantia nigra. Projections from motor cortical regions representing different body parts terminate in different regions of these nuclei. Basal ganglia neurons respond not only to the stimulation of the corresponding regions of the motor cortices, but also to active and passive movements of the corresponding body parts. On the basis of these anatomical and physiological findings, somatotopic organization can be identified in the motor territories of these nuclei in the basal ganglia. In addition, projections from functionally interrelated cortical areas partially converge through the cortico-basal ganglia loop, but nevertheless the somatotopy is still preserved. Disorganized somatotopy may explain, at least in part, the pathophysiology of movement disorders, such as Parkinson’s disease and dystonia.

  16. 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.

  17. Alveolar proteinosis lung lavage using partial cardiopulmonary bypass.

    OpenAIRE

    Freedman, A P; Pelias, A; Johnston, R F; Goel, I P; Hakki, H I; Oslick, T; Shinnick, J P

    1981-01-01

    An adult case of pulmonary alveolar proteinosis presented with an arterial oxygen tension of 27 mmHg (3.6 kPa) while breathing air. Dangerous hypoxaemia during lung lavage was avoided by using partial cardiopulmonary bypass.

  18. Pulmonary Alveolar Proteinosis: A Rare Cause of Respiratory Failure.

    Science.gov (United States)

    Munir, Zeeshan; Khosa, Muhammad Zeeshan; Qazi, Muhammad Yaqoob

    2015-07-01

    Pulmonary Alveolar Proteinosis (PAP) is a rare syndrome in the paediatric age group and characterized by intra-alveolar accumulation of proteinaceous phospholipid-laden material called surfactant. The diagnosis is made by High Resolution Computed Tomography (HRCT) chest which shows characteristic crazy paving appearance and diagnosis confirmed by Bronchoalveolar Lavage (BAL). We report two cases. First was a 9-month old infant who presented with respiratory distress and peripheral cyanosis since birth. He was diagnosed on High Resolution Computed Tomography (HRCT) chest as a case of pulmonary alveolar proteinosis and broncho-alveolar lavage confirmed his diagnosis. Second case was a 10-year old female child who had a history of repeated chest infections for 5 years and now presented with cough and respiratory distress for 45 days. She was also diagnosed on HRCT chest but unfortunately she died before bronchoalveolar lavage. PMID:26208564

  19. The role of synthetic biomaterials in resorptive alveolar bone regeneration

    Directory of Open Access Journals (Sweden)

    Kaličanin Biljana M.

    2007-01-01

    Full Text Available The alveolar bone tissue resorption defect has a significant role in dentistry. Because of the bone tissue deficit developed by alveolar resorption, the use of synthetic material CP/PLGA (calcium-phosphate/polylactide-co-gliycolide composite was introduced. Investigations were performed on rats with artificially produced resorption of the mandibular bone. The results show that the best effect on alveolar bone were attained by using nano-composite implants. The effect of the nanocomposite was ascertained by determining the calcium and phosphate content, as a basis of the hydroxyapatite structure. The results show that synthetic CP/PLGA nanocomposite alleviate the rehabilitation of weakened alveolar bone. Due to its osteoconductive effect, CP/PLGA can be the material of choice for bone substitution in the future.

  20. Alveolar lymphangioma in infants: report of two cases.

    LENUS (Irish Health Repository)

    FitzGerald, Kirsten

    2009-06-01

    The alveolar lymphangioma is a benign but relatively rare condition found only in the oral cavities of black infants. Dentists practising in Ireland may be unaware of this condition due to its racial specificity. This paper presents two case reports of multiple alveolar lymphangiomas found in black infants in a children\\'s hospital in Ireland. The epidemiology, aetiology, clinical presentation, histology, and management options are discussed. The photographs should aid the practitioner in recognising these lesions.

  1. Alveolar lymphangioma in infants: report of two cases.

    LENUS (Irish Health Repository)

    FitzGerald, Kirsten

    2012-02-01

    The alveolar lymphangioma is a benign but relatively rare condition found only in the oral cavities of black infants. Dentists practising in Ireland may be unaware of this condition due to its racial specificity. This paper presents two case reports of multiple alveolar lymphangiomas found in black infants in a children\\'s hospital in Ireland. The epidemiology, aetiology, clinical presentation, histology, and management options are discussed. The photographs should aid the practitioner in recognising these lesions.

  2. Dynamics of surfactant release in alveolar type II cells

    OpenAIRE

    Haller, Thomas; Ortmayr, Jörg; Friedrich, Franz; Völkl, Harald; Dietl, Paul

    1998-01-01

    Pulmonary surfactant, secreted via exocytosis of lamellar bodies (LB) by alveolar type II (AT II) cells, maintains low alveolar surface tension and is therefore essential for normal lung function. Here we describe real-time monitoring of exocytotic activity in these cells by visualizing and quantifying LB fusion with the plasma membrane (PM). Two approaches were used. First, fluorescence of LysoTracker Green DND-26 (LTG) in LB disappeared when the dye was released after exocytosis. Second, ph...

  3. Identification of a cell membrane protein that binds alveolar surfactant.

    OpenAIRE

    Strayer, D. S.

    1991-01-01

    Alveolar surfactants are complex mixtures of proteins and phospholipids produced by type II alveolar cells and responsible for lowering pulmonary surface tension. The process by which surfactant is produced and exported and by which its production by pulmonary cells is regulated are not well understood. This study was designed to identify a cellular receptor for surfactant constituents. To do so, monoclonal anti-idiotypic antibodies directed against antibodies to porcine and rabbit surfactant...

  4. Dynamic thermal performance of alveolar brick construction system

    International Nuclear Information System (INIS)

    Highlights: → Even though U-value does not measure thermal inertia, it is the commonly used parameter. → The thermal performance analysis of buildings must include the evaluation of transient parameters. → Transient parameters of alveolar brick constructive system show good agreement with its low energy consumption. -- Abstract: Alveolar bricks are being introduced in building sector due to the simplicity of their construction system and to the elimination of the insulation material. Nevertheless, it is not clear if this new system is energetically efficient and which is its thermal behaviour. This paper presents an experimental and theoretical study to evaluate the thermal behaviour of the alveolar brick construction system, compared with a traditional Mediterranean brick system with insulation. The experimental study consists of measuring the thermal performance of four real house-like cubicles. The thermal transmittance in steady-state, also known as U-value, is calculated theoretically and experimentally for each cubicle, presenting the insulated cubicles as the best construction system, with differences around 45% in comparison to the alveolar one. On the other hand, experimental results show significantly smaller differences on the energy consumption between the alveolar and insulated construction systems during summer period (around 13% higher for the alveolar cubicle). These values demonstrate the high thermal efficiency of the alveolar system. In addition, the lack of agreement between the measured energy consumption and the calculated U-values, guides the authors to analyze the thermal inertia of the different building components. Therefore, several transient parameters, extracted from the heat transfer matrix and from experimental data, are also evaluated. It can be concluded that the alveolar brick construction system presents higher thermal inertia than the insulated one, justifying the low measured energy consumption.

  5. 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...

  6. Is alveolar cleft reconstruction still controversial? (Review of literature)

    OpenAIRE

    Seifeldin, Sameh A.

    2015-01-01

    Cleft lip and palate (CL/P) is a frequent congenital malformation that manifests in several varieties including unilateral or bilateral and complete or incomplete. Alveolar cleft reconstruction remains controversial with regard to timing, graft materials, surgical techniques, and methods of evaluation. Many studies have been conducted addressing these points to develop an acceptable universal protocol for managing CL/P. The primary goal of alveolar cleft reconstruction in CL/P patients is to ...

  7. Familial occurrence of pulmonary alveolar microlithiasis in 3-siblings

    International Nuclear Information System (INIS)

    Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown etiology characterized by intra-alveolar calcium deposits. More than 500 cases were reported in the literature. The disorder affects people at every age beginning from the early childhood. It occurs probably as a result of autosomal recessive transmission. Familial occurrence is often found with family history of the disease being present in up to 50% of the reported cases. We report PAM in 3 siblings. (author)

  8. Alveolar proteinosis in Behçet's disease

    OpenAIRE

    Tetikkurt Cuneyt; Tetikkurt Seza; Ozdemir Imran; Zuhur Cigdem; Bayar Nihal

    2010-01-01

    Abstract A 51-year-old man with Behçet's disease complained of fever, dry cough and dyspnea during exertion. Chest CT showed ground glass opacities with interstitial septal thickening in both lungs. Bronchoalveolar lavage (BAL) revealed amorphous and lipoproteinaceous material that was periodic acid-Schiff (PAS) stain positive. Transbronchial biopsy specimen demonstrated PAS positive alveolar eosinophilic material consistent with pulmonary alveolar proteinosis. Serum anti-granulocyte-macropha...

  9. Anaesthetic management of bilateral alveolar proteinosis for bronchopulmonary lavage.

    Directory of Open Access Journals (Sweden)

    Dixit R

    1998-01-01

    Full Text Available The most hazardous manifestation of pulmonary alveolar proteinosis is progressive hypoxia for which bronchopulmonary lavage (BPL is the single most effective treatment. Unfortunately this procedure under general anesthesia itself increases the risk of hypoxia due to the need for one lung ventilation. It was therefore considered interesting to report the successful anaesthetic management of a patient with pulmonary alveolar proteinosis for Bronchopulmonary lavage.

  10. Alveolar proteinosis and nocardiosis: a patient treated by bronchopulmonary lavage.

    OpenAIRE

    Pascual, J.; Gómez Aguinaga, M. A.; Vidal, R; Maudes, A.; Sureda, A.; Gómez Mampaso, E.; Fogué, L.

    1989-01-01

    Alveolar proteinosis is a relatively rare disease of unclear pathogenesis associated with opportunistic-infections. Although nocardiosis is the most frequent one, only 22 cases have been reported previously and are reviewed here. We present a patient with alveolar proteinosis with nocardiosis treated as an emergency with bilateral bronchopulmonary lavage and antibiotics. No previous cases of this association have been successfully managed in this way.

  11. 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...

  12. 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

  13. Horizontal alveolar bone loss: A periodontal orphan

    Directory of Open Access Journals (Sweden)

    Jayakumar A

    2010-01-01

    Full Text Available Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician′s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs (of patients diagnosed with chronic periodontitis and seeking periodontal care, which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36% OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2% teeth, and vertical defects were found only in 264 (7.8% of the teeth, which was statistically significant (P<.001. Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3% have addressed vertical bone loss, and 18 (3.7% have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment

  14. Epithelial antimicrobial peptides in host defense against infection

    Directory of Open Access Journals (Sweden)

    Bals Robert

    2000-10-01

    Full Text Available Abstract One component of host defense at mucosal surfaces seems to be epithelium-derived antimicrobial peptides. Antimicrobial peptides are classified on the basis of their structure and amino acid motifs. Peptides of the defensin, cathelicidin, and histatin classes are found in humans. In the airways, α-defensins and the cathelicidin LL-37/hCAP-18 originate from neutrophils. β-Defensins and LL-37/hCAP-18 are produced by the respiratory epithelium and the alveolar macrophage and secreted into the airway surface fluid. Beside their direct antimicrobial function, antimicrobial peptides have multiple roles as mediators of inflammation with effects on epithelial and inflammatory cells, influencing such diverse processes as proliferation, immune induction, wound healing, cytokine release, chemotaxis, protease-antiprotease balance, and redox homeostasis. Further, antimicrobial peptides qualify as prototypes of innovative drugs that might be used as antibiotics, anti-lipopolysaccharide drugs, or modifiers of inflammation.

  15. Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages

    Directory of Open Access Journals (Sweden)

    Dagmar A. Kuhn

    2014-09-01

    Full Text Available Precise knowledge regarding cellular uptake of nanoparticles is of great importance for future biomedical applications. Four different endocytotic uptake mechanisms, that is, phagocytosis, macropinocytosis, clathrin- and caveolin-mediated endocytosis, were investigated using a mouse macrophage (J774A.1 and a human alveolar epithelial type II cell line (A549. In order to deduce the involved pathway in nanoparticle uptake, selected inhibitors specific for one of the endocytotic pathways were optimized regarding concentration and incubation time in combination with fluorescently tagged marker proteins. Qualitative immunolocalization showed that J774A.1 cells highly expressed the lipid raft-related protein flotillin-1 and clathrin heavy chain, however, no caveolin-1. A549 cells expressed clathrin heavy chain and caveolin-1, but no flotillin-1 uptake-related proteins. Our data revealed an impeded uptake of 40 nm polystyrene nanoparticles by J774A.1 macrophages when actin polymerization and clathrin-coated pit formation was blocked. From this result, it is suggested that macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play a crucial role. The uptake of 40 nm nanoparticles in alveolar epithelial A549 cells was inhibited after depletion of cholesterol in the plasma membrane (preventing caveolin-mediated endocytosis and inhibition of clathrin-coated vesicles (preventing clathrin-mediated endocytosis. Our data showed that a combination of several distinguishable endocytotic uptake mechanisms are involved in the uptake of 40 nm polystyrene nanoparticles in both the macrophage and epithelial cell line.

  16. MRI of the basal ganglia calcification

    International Nuclear Information System (INIS)

    MR imaging was performed for 11 patients (9 in Down's syndrome and 2 in idiopathic intracerebral calcification) who showed calcifications in bilateral basal ganglia on CT. High signal intensity in the basal ganglia was found only in one patient with idiopathic intracerebral calcification on T1-weighted image. The calcified areas of all patients in Down's syndrome did not show high signal intensity on T1-weighted image. The exact reasons why MRI exhibits the different signal intensities in calcified tissue on T1-weighted image are unknown. Further clinical investigations will be needed. (author)

  17. The connectome of the basal ganglia.

    Science.gov (United States)

    Schmitt, Oliver; Eipert, Peter; Kettlitz, Richard; Leßmann, Felix; Wree, Andreas

    2016-03-01

    The basal ganglia of the laboratory rat consist of a few core regions that are specifically interconnected by efferents and afferents of the central nervous system. In nearly 800 reports of tract-tracing investigations the connectivity of the basal ganglia is documented. The readout of connectivity data and the collation of all the connections of these reports in a database allows to generate a connectome. The collation, curation and analysis of such a huge amount of connectivity data is a great challenge and has not been performed before (Bohland et al. PloS One 4:e7200, 2009) in large connectomics projects based on meta-analysis of tract-tracing studies. Here, the basal ganglia connectome of the rat has been generated and analyzed using the consistent cross-platform and generic framework neuroVIISAS. Several advances of this connectome meta-study have been made: the collation of laterality data, the network-analysis of connectivity strengths and the assignment of regions to a hierarchically organized terminology. The basal ganglia connectome offers differences in contralateral connectivity of motoric regions in contrast to other regions. A modularity analysis of the weighted and directed connectome produced a specific grouping of regions. This result indicates a correlation of structural and functional subsystems. As a new finding, significant reciprocal connections of specific network motifs in this connectome were detected. All three principal basal ganglia pathways (direct, indirect, hyperdirect) could be determined in the connectome. By identifying these pathways it was found that there exist many further equivalent pathways possessing the same length and mean connectivity weight as the principal pathways. Based on the connectome data it is unknown why an excitation pattern may prefer principal rather than other equivalent pathways. In addition to these new findings the local graph-theoretical features of regions of the connectome have been determined. By

  18. Basal Cell Carcinoma in a Child

    OpenAIRE

    Samet Vasfi Kuvat; Zuhal Gücin; Barış Keklik; Gülzade Özyalvaçlı; Karaca Başaran

    2011-01-01

    Basal cell carcinoma is the most commonly seen nonmelanoma skin cancer which is rarely encountered in the childhood period. An 11-year old child was admitted to our clinic due to an erythematous and a slightly pigmented lesion with a 3 × 4 cm diameter on his posterior scalp. Macroscopically, the lesion was excised with a 10 mm safety margin. Pathologic examination revealed a basal cell carcinoma. No symptoms or signs of a syndrome were observed both in the patient and his family.

  19. Spontaneous Resolution of Retinal Pigment Epithelial Detachments and Visual Improvement in Patient with MPGN II: A Case Report

    Directory of Open Access Journals (Sweden)

    T. Empeslidis

    2012-01-01

    Full Text Available A 31-year-old female suffering from membranoproliferative glomerulonephritis type II (MPGN II presented to the Eye Casualty Department reporting a history of blurred and distorted vision. The patient appeared to have drusenoid retinal epithelial detachments and minimal intraretinal fluid. The subretinal deposits, basal lamina drusen, and pigment epithelial detachment appeared to resemble a “stars in the sky” picture with no symmetry between the eyes. The retinal pigment epithelial detachments improved and flattened over 18 month. and the best corrected visual acuity improved in the most affected eye. There was no evidence of neovascularization, and the intraretinal fluid disappeared spontaneously.

  20. Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells

    Directory of Open Access Journals (Sweden)

    Richter Joachim

    2008-01-01

    Full Text Available Abstract Background Prophylactic exogenous surfactant therapy is a promising way to attenuate the ischemia and reperfusion (I/R injury associated with lung transplantation and thereby to decrease the clinical occurrence of acute lung injury and acute respiratory distress syndrome. However, there is little information on the mode by which exogenous surfactant attenuates I/R injury of the lung. We hypothesized that exogenous surfactant may act by limiting pulmonary edema formation and by enhancing alveolar type II cell and lamellar body preservation. Therefore, we investigated the effect of exogenous surfactant therapy on the formation of pulmonary edema in different lung compartments and on the ultrastructure of the surfactant producing alveolar epithelial type II cells. Methods Rats were randomly assigned to a control, Celsior (CE or Celsior + surfactant (CE+S group (n = 5 each. In both Celsior groups, the lungs were flush-perfused with Celsior and subsequently exposed to 4 h of extracorporeal ischemia at 4°C and 50 min of reperfusion at 37°C. The CE+S group received an intratracheal bolus of a modified natural bovine surfactant at a dosage of 50 mg/kg body weight before flush perfusion. After reperfusion (Celsior groups or immediately after sacrifice (Control, the lungs were fixed by vascular perfusion and processed for light and electron microscopy. Stereology was used to quantify edematous changes as well as alterations of the alveolar epithelial type II cells. Results Surfactant treatment decreased the intraalveolar edema formation (mean (coefficient of variation: CE: 160 mm3 (0.61 vs. CE+S: 4 mm3 (0.75; p 3 (0.90 vs. CE+S: 0 mm3; p 3 (0.39 vs. CE+S: 268 mm3 (0.43; p 3(0.10 and CE+S (481 μm3(0.10 compared with controls (323 μm3(0.07; p Conclusion Intratracheal surfactant application before I/R significantly reduces the intraalveolar edema formation and development of atelectases but leads to an increased development of