Mechanisms Of Alveolar Protein Clearance In The Intact Lung
acute respiratory distress syndrome; air-blood barrier; apoprotein sp-a; bronchoalveolar lavage fluid; diffusion; endocytosis; epithelial-cell monolayers; ii cells; instillation; intratracheal; junctions; opens tight; perfused rabbit lungs; Physiology; protein; rat lung; Respiratory System; respiratory-distress syndrome; transport pulmonary edema
Transport of protein across the alveolar epithelial barrier is a critical process in recovery from pulmonary edema and is also important in maintaining the alveolar milieu in the normal healthy lung. Various mechanisms have been proposed for clearing alveolar protein, including transport by the mucociliary escalator, intra-alveolar degradation, or phagocytosis by macrophages. However, the most likely processes are endocytosis across the alveolar epithelium, known as transcytosis, or paracellular diffusion through the epithelial barrier. This article focuses on protein transport studies that evaluate these two potential mechanisms in whole lung or animal preparations. When protein concentrations in the air spaces are low, e. g., albumin concentrations <0.5 g/100 ml, protein transport demonstrates saturation kinetics, temperature dependence indicating high energy requirements, and sensitivity to pharmacological agents that affect endocytosis. At higher concentrations, the protein clearance rate is proportional to protein concentration without signs of saturation, inversely related to protein size, and insensitive to endocytosis inhibition. Temperature dependence suggests a passive process. Based on these findings, alveolar albumin clearance occurs by receptor-mediated transcytosis at low protein concentrations but proceeds by passive paracellular mechanisms at higher concentrations. Because protein concentrations in pulmonary edema fluid are high, albumin concentrations of 5 g/100 ml or more, clearance of alveolar protein occurs by paracellular pathways in the setting of pulmonary edema. Transcytosis may be important in regulating the alveolar milieu under nonpathological circumstances. Alveolar degradation may become important in long-term protein clearance, clearance of insoluble proteins, or under pathological conditions such as immune reactions or acute lung injury.
Hastings R H; Folkesson H G; Matthay M A
American Journal of Physiology-Lung Cellular and Molecular Physiology
2004
2004-04
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1152/ajplung.00205.2003" target="_blank" rel="noreferrer noopener">10.1152/ajplung.00205.2003</a>
Mild acidic pH inhibition of the major pathway of herpes simplex virus entry into HEp-2 cells.
Animals; Cell Line; Electron; Electrophoresis; Endocytosis; Glycoproteins/analysis; Glycosylation; Humans; Hydrogen-Ion Concentration; Microscopy; Polyacrylamide Gel; Simplexvirus/*physiology/ultrastructure; Temperature; Time Factors; Vero Cells; Viral Proteins/analysis/metabolism
Penetration of the KOS strain of herpes simplex virus type 1 (HSV-1) and the MS and 333 strains of herpes simplex virus type 2 (HSV-2) into HEp-2 cells at pH 6.3 was at least 100-fold less efficient than at pH 7.4. Penetration of two low passage clinical isolates was completely blocked at pH 6.3. The syncytium-forming
Rosenthal K S; Killius J; Hodnichak C M; Venetta T M; Gyurgyik L; Janiga K
The Journal of general virology
1989
1989-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1099/0022-1317-70-4-857" target="_blank" rel="noreferrer noopener">10.1099/0022-1317-70-4-857</a>
Herpes simplex virus type 1 penetration initiates mobilization of cell surface proteins.
Animals; Hydrogen-Ion Concentration; In Vitro Techniques; Actin Cytoskeleton/physiology; Vero Cells; Microscopy; Endocytosis; Amantadine/analogs & derivatives/pharmacology; Colchicine/pharmacology; Cytochalasin B/pharmacology; Herpes Simplex/*physiopathology; Membrane Fluidity; Membrane Proteins/*physiology; Microtubules/physiology; Simplexvirus/*physiology; Fluorescence
Changes in membrane structure resulting from herpes simplex virus 1 (HSV-1) penetration were detected using fluorescence photobleaching recovery methods. The effect could be blocked by inhibitors of viral and cellular processes involved in virus penetration. A rapid mode of HSV-1 strain KOS penetration into VERO cells at 37 degrees C normally occurs after a 5 min lag period and is 90-95% complete within 20-30 min. Rates of cell surface protein diffusion increase 2-3-fold after 5 min and return to normal after 25-30 min, this return correlating temporally with the penetration of the virus. At pH 6.3 the lag period preceeding penetration of HSV is increased to 20 min and penetration proceeds much more slowly than at pH 7.4. Inhibition of virus penetration with cytochalasin B or with the antiherpes drug tromantadine also prevents the HSV-1-induced increase in cell surface protein mobility. Colchicine, which does not block HSV-1 penetration, prevents the recovery of the membrane following virus penetration. Therefore, the changes in membrane structure characterized by increased cell surface protein mobility seem to be caused by virus penetration. Cytoskeletal function and integrity are required for the initiation of, and cell recovery from, virus penetration. A pH-sensitive activity, likely to be a virion fusion glycoprotein, is also required.
Rosenthal K S; Roess D; Barisas B G
Biochimica et biophysica acta
1988
1988-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0005-2736(88)90272-6" target="_blank" rel="noreferrer noopener">10.1016/0005-2736(88)90272-6</a>