Mechanisms Of Alveolar Protein Clearance In The Intact Lung

Mechanisms Of Alveolar Protein Clearance In The Intact Lung

Hastings R H; Folkesson H G; Matthay M A

American Journal of Physiology-Lung Cellular and Molecular Physiology

2004

2004-04

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.

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

Journal Article or Conference Abstract Publication

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

L679-L689

4

286