ENDOTHELIAL SERPINS - PROTECTORS OF THE VASCULATURE

Vascular damage, initiated by host inflammatory cells, is a component of the pathophysiology of many acute and chronic inflammatory disorder s. Neutrophil-mediated tissue damage is mediated primarily by proteina ses, particularly elastase and cathepsin G. In this study we have iden tified endothelial binding of two key serine proteinase inhibitors (se rpins), alpha(1)-antitrypsin, the inhibitor of elastase, and alpha(1)- antichymotrypsin, the inhibitor of cathepsin G. These serpins are shed from the endothelium into the supernatant when neutrophils adherent t o the endothelium are activated. Endothelium activated by lipopolysacc haride (LPS) augments this process. Serpin-proteinase complexes activa te neutrophils and induce further cytokine release, thereby amplifying inflammatory processes. Strategies aimed at preventing endothelial se rpin depletion may help minimize vascular damage during inflammation.