PROGRESSIVE INACTIVATION OF CATHEPSIN-G AND ELASTASE RELEASED FROM ACTIVATED NEUTROPHILS IN-VITRO - LACK OF PARTICIPATION OF THE NEUTROPHILALPHA(1)-PROTEINASE INHIBITOR

Addition of platelets to activated human polymorphonuclear neutrophils (PMNs) led to their aggregation and degranulation, with these respons es decreasing as a function of the time interval between PMN activatio n and platelet addition. Thus, for a 15-second interval platelet aggre gation and serotonin release reached 51.3% +/- 6.7% (n = 11) and 64.3% +/- 4.9% (n = 8), respectively, but after a 5-minute interval they we re totally absent. This effect was correlated with the decrease in enz ymatic activities of elastase (HLE) and cathepsin G (CAT-G) that were released on PMN activation and responsible for the activation of nearb y platelets (r = 0.86 and 0.90 for CAT-G and HLE, respectively; p < 0. 05). Because it has been recently shown that PMNs express an alpha(1)- proteinase inhibitor (alpha(1)-PI) gene and secrete this antiproteinas e at their surface, we investigated whether the PMN alpha(1)-PI could regulate the biologic activities of both proteinases. Although superox ide anions oxidize alpha(1)-PI and reduce its affinity for CAT-G and H LE, maneuvers aimed at modifying their concentrations did not modify t he loss of CAT-G and HLE. In fact, the progressive decrease of the two proteinase enzymatic activities followed the same pattern whether PMN s were present or not. It is concluded that PMN alpha(1)-PI is not inv olved in the time-dependent inactivation of CAT-G and HLE released fro m activated PMNs.