Inhibition of Polymorphonuclear Leukocyte-Mediated Endothelial Cell Detachment by Antileukoprotease: A Comparison with Other Proteinase Inhibitors

Abstract The role of elastase and proteinase inhibitors in polymorphonuclear leukocyte(PMN)mediated injury to human umbilical cord venous endothelial cells (HUVEC) was investigated. Both purified human neutrophil elastase and PMN that were stimulated with serum-treated zymosan (STZ) induced detachment, but not lysis of HUVEC. PMN-, but not purified elastase-mediated detachment was enhanced by the presence of methionine, which indicates a role for reactive oxygen metabolites in PMN-mediated HUVEC detachment. Detachment of HUVEC could be inhibited by secretory leukocyte proteinase inhibitor or antileukoprotease (ALP), al-proteinase inhibitor (α1-PI) and N-methoxy-succinyl-ala-ala-pro-val-chloromethyl ketone (CMK). At concentrations at which elastase-mediated detachment was maximally inhibited, ALP and CMK, but not α1-PI, were also able to inhibit maximally PMN-mediated detachment. An explanation for this difference could be that the larger size of α1-PI reduces the access of α1-PI to the interface between the PMN and the HUVEC.