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127976 - Regulation of Fibrinolytic Activity of Neutrophil Leukocyte Elastase.pdf (564.33 kB)

Regulation of fibrinolytic activity of neutrophil leukocyte elastase, plasmin, and miniplasmin by plasma protease inhibitors

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posted on 2023-05-19, 20:45 authored by Kolev, K, Lerant, I, Kiril TenekedjievKiril Tenekedjiev, Machovich, R
The effect of solid-phase fibrin on the inactivation of plasmin, miniplasmin, and neutrophil leukocyte elastase (PMN-elastase) by plasma protease inhibitors (alpha 2-antiplasmin, alpha 1-protease inhibitor, alpha 2-macroglobulin) was studied. In Hanks' balanced salt solution, fibrin reduces the second-order rate constant for the inhibition of PMN-elastase by alpha 1-protease inhibitor from 8,760 x 10(4) to 4 x 10(4) M-1.s-1 and by alpha 2-macroglobulin from 121 x 10(4) to 1.8 x 10(4) M-1.s-1. The rate constant for miniplasmin inactivation by alpha 2-antiplasmin decreases from 99 x 10(4) to 1 x 10(4) M-1.s-1, by alpha 2-macroglobulin from 78 x 10(4) to 1.8 x 10(4) M-1.s-1, and by alpha 1-protease inhibitor from 0.11 x 10(4) M-1.s-1 to 0. Plasmin bound to fibrin is completely protected against alpha 2-macroglobulin and alpha 1-protease inhibitor, whereas the rate constant for the inactivation by its primary plasma inhibitor alpha 2-antiplasmin is reduced from 430 x 10(4) to 1.08 x 10(4) M-1.s-1. The competition of substrate and inhibitor for the enzyme was also studied, using fibrin preincubated with inhibitor. Under our pseudo-first-order experimental conditions, fibrin completely eliminates those interactions, the second-order rate constant of which is 1.1 x 10(5) M-1.s-1 or less in a system without fibrin surface.

History

Publication title

Journal of Biological Chemistry

Volume

269

Issue

25

Pagination

17030-17034

ISSN

0021-9258

Department/School

Australian Maritime College

Publisher

American Society for Biochemistry and Molecular Biology, Inc.

Place of publication

USA

Rights statement

This research was originally published in the Journal of Biological Chemistry. Kolev, Krasimir and Lerant, Istvan and Tenekedjiev, Kiril and Machovich, Raymund. Regulation of fibrinolytic activity of neutrophil leukocyte elastase, plasmin, and miniplasmin by plasma protease inhibitors. J. Biol. Chem. 1994; Vol. 269, No. 25, pp. 17030-17034. © 1994 the American Society for Biochemistry and Molecular Biology.

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