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Protective effect of platelet activating factor antagonists on cultured endothelial cell lysis induced by elastase or activated neutrophils
Author(s) -
Renesto Patricia,
Vicart Patrick,
Paulin Denise,
Chignard Michel
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15278.x
Subject(s) - platelet activating factor , lysis , elastase , cytotoxicity , endothelial stem cell , platelet , cell culture , pharmacology , pancreatic elastase , receptor , microbiology and biotechnology , chemistry , immunology , biology , biochemistry , in vitro , enzyme , genetics
1 The mechanism(s) responsible for injury of endothelial cells induced by human leukocyte elastase (HLE) was investigated in an immortalized venous human endothelial cell line (IVEC). 2 First, the proteinase concentrations and incubation delays necessary to trigger a significant IVEC cytotoxicity were determined by chromium assays. Thus, exposure of IVEC for 6 h to 10 μ ml −1 HLE resulted in 22 ± 2.8% lysis and 36.4 ± 5.4% detachment (mean ± s.e. mean; n = 4; P < 0.05). 3 WEB 2086, a specific platelet‐activating factor (PAF) receptor antagonist, induced a significant concentration‐dependent decrease of such a lysis (39.6 ± 7.7% protection at 100 μ n = 4). This potential role for PAF was confirmed with two other antagonists of this lipid mediator, i.e., BN 52021 and RP 48740. 4 Finally, we demonstrated that pretreatment of IVEC with WEB 2086 protected significantly against cell lysis induced by stimulated human neutrophils, an experimental model in which HLE participates.