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Alveolar Epithelium

The Experts below are selected from a list of 261 Experts worldwide ranked by ideXlab platform

Michael A Matthay – 1st expert on this subject based on the ideXlab platform

  • the Alveolar Epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor
    Thorax, 2007
    Co-Authors: Julie A Bastarache, Ling Wang, Michael A Matthay, Thomas Geiser, Zhengming Wang, Kurt H Albertine, Lorraine B Ware

    Abstract:

    Background: The Alveolar compartment is a procoagulant antifibrinolytic environment in acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A study was undertaken to test the hypothesis that the Alveolar Epithelium can initiate intra-Alveolar coagulation by expressing active tissue factor (TF). Methods: Using an in vitro cell surface TF assay and TF ELISA, the activity and production of TF in cultured Alveolar epithelial (A549) cells following exposure to cytomix (tumour necrosis factor α, interleukin 1β and interferon γ) was measured. TF gene transcription was measured by semi-quantitative reverse-transcription PCR. Immunohistochemistry for TF was performed on lung sections from patients with ARDS and controls. TF protein levels were measured by ELISA in undiluted pulmonary oedema fluid from patients with ALI/ARDS and compared with control patients with hydrostatic pulmonary oedema. Results: TF activity, mRNA and protein levels increased in A549 cells after stimulation with cytomix. Increased TF activity was also seen in A549 cells following incubation with pulmonary oedema fluid from patients with ALI/ARDS. Immunohistochemistry for TF in human lung tissue from patients with ARDS showed prominent TF staining in Alveolar epithelial cells as well as intra-Alveolar macrophages and hyaline membranes. TF antigen levels in oedema fluid (median 37 113 (IQR 14 956–73 525) pg/ml) were significantly higher than in plasma (median 336 (IQR 165–669) pg/ml, p Conclusions: The Alveolar Epithelium is capable of modulating intra-Alveolar coagulation through upregulation of TF following exposure to inflammatory stimuli and may contribute to intra-Alveolar fibrin deposition in ARDS.

  • novel role of the human Alveolar Epithelium in regulating intra Alveolar coagulation
    American Journal of Respiratory Cell and Molecular Biology, 2007
    Co-Authors: Ling Wang, Julie A Bastarache, Nancy Wickersham, Xiaohui Fang, Michael A Matthay, Lorraine B Ware

    Abstract:

    Intra-Alveolar fibrin deposition is a common response to localized and diffuse lung infection and acute lung injury (ALI). We hypothesized that the Alveolar Epithelium modulates intra-Alveolar fibrin deposition through activation of protein C. Our obejctives were to determine whether components of the protein C activation pathway are present in the Alveolar compartment in ALI and whether Alveolar Epithelium is a potential source. In patients with ALI, pulmonary edema fluid levels of endothelial protein C receptor (EPCR) were higher than plasma, suggesting a source in the lung. To determine whether Alveolar epithelial cells are a potential source, protein C activation by A549, small airway epithelial, and primary human Alveolar epithelial type II cells was measured. All three cell types express thrombomodulin (TM) and EPCR, and activate protein C on the cell surface. Activation of protein C was inhibited by cytomix (TNF-α, IL-1β, and IFN-γ). Release of EPCR and TM into the conditioned medium was inhibited …

  • bench to bedside review the role of the Alveolar Epithelium in the resolution of pulmonary edema in acute lung injury
    Critical Care, 2004
    Co-Authors: Rachel L Zemans, Michael A Matthay

    Abstract:

    Clearance of pulmonary edema fluid is accomplished by active ion transport, predominantly by the Alveolar Epithelium. Various ion pumps and channels on the surface of the Alveolar epithelial cell generate an osmotic gradient across the Epithelium, which in turn drives the movement of water out of the airspaces. Here, the mechanisms of Alveolar ion and fluid clearance are reviewed. In addition, many factors that regulate the rate of edema clearance, such as catecholamines, steroids, cytokines, and growth factors, are discussed. Finally, we address the changes to the Alveolar Epithelium and its transport processes during acute lung injury (ALI). Since relevant clinical outcomes correlate with rates of edema clearance in ALI, therapies based on our understanding of the mechanisms and regulation of fluid transport may be developed.

Kristin Westphalen – 2nd expert on this subject based on the ideXlab platform

  • real time microscopy of interactions between Alveolar macrophages and the Alveolar Epithelium in situ
    European Respiratory Journal, 2014
    Co-Authors: Kristin Westphalen, Jahar Bhattacharya

    Abstract:

    Background: Alveolar macrophages (AMs) are the first line of defense in the lung. The mechanisms of how Alveolar macrophages interact with the Alveolar Epithelium to modulate lung inflammation are not well defined. Methods: To visualize AMs in situ , we expressed Enhanced Yellow Fluorescent Protein in CD11c+ AMs (AMYFP). We isolated and blood-perfused lungs of AMYFP mice at constant pulmonary artery, left atrial and Alveolar pressures of 10, 3 and 5 cmH2O, respectively. We imaged the lungs by confocal microscopy. We micropunctured single alveoli and microinfused dyes and reagents. To define the role of gap junctional channels (GJCs) in lung injury, we crossed AMYFP mice with Cx43floxed/floxed mice (AMYFPCx43-/-). We treated mice with intra-nasal instillations of 1 mg/kg LPS 24 h before we excised the lungs. Results: Calcium uncaging experiments in wild type mice revealed that 38±10% of all AMs formed functional GJCs with the Alveolar Epithelium. As compared to wild type mice, AM-specific knockout of Cx43 in AMCx43-/- mice resulted in a 2-fold higher neutrophil recruitment to the lung 24 h after LPS and reduced survival after 25 mg/kg LPS (P<0.05). Cytokines of macrophages origin (MIP-1alpha) but also cytokines that were predominantly of epithelial origin (CXCL1 and 5) were increased in the bronchoAlveolar lavage, suggesting that AM-epithelial communication may serve as a feedback loop to regulate lung inflammation. Conclusions: For the first time, we report that AMs form GJCs with the Alveolar Epithelium. The interaction between AMs and the Epithelium through GJCs was crucial in that knockout of GJCs in AMs aggravated lung injury (HL78645, HL64896).

  • Real-time microscopy of interactions between Alveolar macrophages and the Alveolar Epithelium in situ
    European Respiratory Journal, 2014
    Co-Authors: Kristin Westphalen, Jahar Bhattacharya

    Abstract:

    Background: Alveolar macrophages (AMs) are the first line of defense in the lung. The mechanisms of how Alveolar macrophages interact with the Alveolar Epithelium to modulate lung inflammation are not well defined. Methods: To visualize AMs in situ , we expressed Enhanced Yellow Fluorescent Protein in CD11c+ AMs (AMYFP). We isolated and blood-perfused lungs of AMYFP mice at constant pulmonary artery, left atrial and Alveolar pressures of 10, 3 and 5 cmH2O, respectively. We imaged the lungs by confocal microscopy. We micropunctured single alveoli and microinfused dyes and reagents. To define the role of gap junctional channels (GJCs) in lung injury, we crossed AMYFP mice with Cx43floxed/floxed mice (AMYFPCx43-/-). We treated mice with intra-nasal instillations of 1 mg/kg LPS 24 h before we excised the lungs. Results: Calcium uncaging experiments in wild type mice revealed that 38±10% of all AMs formed functional GJCs with the Alveolar Epithelium. As compared to wild type mice, AM-specific knockout of Cx43 in AMCx43-/- mice resulted in a 2-fold higher neutrophil recruitment to the lung 24 h after LPS and reduced survival after 25 mg/kg LPS (P

Ikumi Tamai – 3rd expert on this subject based on the ideXlab platform

  • experimental evidence for resecretion of pge2 across rat Alveolar Epithelium by oatp2a1 slco2a1 mediated transcellular transport
    Journal of Pharmacology and Experimental Therapeutics, 2019
    Co-Authors: Takeo Nakanishi, Hiroki Takashima, Yuka Uetoko, Hisakazu Komori, Ikumi Tamai

    Abstract:

    Prostaglandin transporter Oatp2a1/Slco2a1 is expressed at the apical (AP) membranes of type-1 Alveolar epithelial (AT1) cells. To investigate the role of OATP2A1 in prostaglandin E2 (PGE2) handling by Alveolar Epithelium, we studied PGE2 transport across and secretion from monolayers of rat AT1-like (AT1-L) cells obtained by trans-differentiation of type-2 Alveolar epithelial cells isolated from male Wistar rats. Rat AT1-L cells expressed Oatp2a1/Slco2a1, together with smaller amounts of Mrp4/Abcc4 and Oct1/Slc22a1. PGE2 uptake was saturable with Km 43.9 ± 21.9 nM. Transcellular transport of PGE2 across AT1-L cells grown on permeable filters in the AP-to-basolateral (BL) direction was 5-fold greater than that in the reverse direction and was saturable with Km 118 ± 26.8 nM; it was significantly inhibited by OATP inhibitors bromosulfophthalein (BSP) and suramin, and an MRP4 inhibitor, Ceefourin 1. We simultaneously monitored the effects of BSP on the distribution of PGE2 produced by bradykinin-treated AT1-L cells and PGE2-d4 externally added on the AP side of the cells. In the presence of BSP, PGE2 increased more rapidly on the AP side, whereas PGE2-d4 decreased more slowly on the AP side. The decrease in PGE2-d4 from the AP side corresponded well to the increase on the BL side, indicating that intracellular metabolism did not occur. These results suggest that Oatp2a1 and Mrp4 mediate transepithelial transport of PGE2 in the AP-to-BL direction. Therefore, OATP2A1 may be an important regulator of PGE2 in Alveolar Epithelium by reducing secretion of PGE2 and facilitating “resecretion” of PGE2 present in the Alveolar lumen to the interstitial space or blood.

  • Experimental Evidence for Resecretion of PGE2 across Rat Alveolar Epithelium by OATP2A1/SLCO2A1-Mediated Transcellular Transport.
    Journal of Pharmacology and Experimental Therapeutics, 2018
    Co-Authors: Takeo Nakanishi, Hiroki Takashima, Yuka Uetoko, Hisakazu Komori, Ikumi Tamai

    Abstract:

    Prostaglandin transporter Oatp2a1/Slco2a1 is expressed at the apical (AP) membranes of type-1 Alveolar epithelial (AT1) cells. To investigate the role of OATP2A1 in prostaglandin E2 (PGE2) handling by Alveolar Epithelium, we studied PGE2 transport across and secretion from monolayers of rat AT1-like (AT1-L) cells obtained by trans-differentiation of type-2 Alveolar epithelial cells isolated from male Wistar rats. Rat AT1-L cells expressed Oatp2a1/Slco2a1, together with smaller amounts of Mrp4/Abcc4 and Oct1/Slc22a1. PGE2 uptake was saturable with Km 43.9 ± 21.9 nM. Transcellular transport of PGE2 across AT1-L cells grown on permeable filters in the AP-to-basolateral (BL) direction was 5-fold greater than that in the reverse direction and was saturable with Km 118 ± 26.8 nM; it was significantly inhibited by OATP inhibitors bromosulfophthalein (BSP) and suramin, and an MRP4 inhibitor, Ceefourin 1. We simultaneously monitored the effects of BSP on the distribution of PGE2 produced by bradykinin-treated AT1-L cells and PGE2-d4 externally added on the AP side of the cells. In the presence of BSP, PGE2 increased more rapidly on the AP side, whereas PGE2-d4 decreased more slowly on the AP side. The decrease in PGE2-d4 from the AP side corresponded well to the increase on the BL side, indicating that intracellular metabolism did not occur. These results suggest that Oatp2a1 and Mrp4 mediate transepithelial transport of PGE2 in the AP-to-BL direction. Therefore, OATP2A1 may be an important regulator of PGE2 in Alveolar Epithelium by reducing secretion of PGE2 and facilitating “resecretion” of PGE2 present in the Alveolar lumen to the interstitial space or blood.