Several lung endothelial functions, including 5-hydroxytryptamine removal and hydrolysis of substrates for angiotensin converting enzyme, are impaired by acute lung injury. It was thought that such changes, by signaling altered functional integrity of the endothelium, would allow early detection of acute lung injury. However, lung injury may concurrently diminish the perfused vascular surface area and thus directly reduce removal. It has proven difficult it distinguish between these two determinants of lung removal, primarily because the endothelial function underlying removal is common to both normal and damaged endothelium. We suggest that a qualitative difference between injured and normal endothelium in vivo would be a better basis to distinguish, unequivocally, between them. Such qualitative distinction seems possible, given recent evidence for the induction of specific membrane (receptor) proteins on endothelial cells in culture during inflammatory and immunological reactions. Detection of these membrane proteins in vivo would provide a highly sensitive and specific method of assessing endothelial integrity. Therefore, recognizing that injured endothelium, at least in cell culture systems, expresses a qualitatively different spectrum of membrane-accessible proteins, we will a) continue development of a method for lactoperoxidase-glucose oxidase radioiodination of surface proteins of endothelial cells in the intact lung. Subsequent homogenization, gel electrophoretic and lectin affinity separation will define the """"""""normal"""""""" spectrum of endothelial membane proteins; b) compare the normal spectrum with that of lungs from animals pretreated with bleamycin or phorbol myristate acetate (PMA) to induce novel proteins in the vascular endothelium; c) develop labelled antibody probes to unique, injury-associated antigens; d) use such probes in vivo to explore the presence (or absence) of these proteins in injured lungs and e) compare endothelial responses to injury, so defined, in vivo and in vitro (cells in culture).
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