Neutrophil-mediated increased permeability of microcarrier-cultured endothelial monolayers: a model for the in vitro study of neutrophil-dependent mediators of vasopermeability
- 30 June 1990
- journal article
- research article
- Published by Canadian Science Publishing in Canadian Journal of Physiology and Pharmacology
- Vol. 68 (7) , 836-844
- https://doi.org/10.1139/y90-127
Abstract
Changes in the permeability of human endothelial monolayers in response to activated human neutrophils were examined in a novel, in vitro model of vasopermeability changes. Microcarrier-cultured human umbilical vein endothelial monolayers were used in a system that responds to histamine. Human neutrophils did not increase Evans Blue staining of the endothelium-covered-microcarriers if added alone or if added with the neutrophil-dependent mediator of vasopermeability, formyl-methionyl-leucyl-phenylalanine (FMLP, 0.1 .mu.M). In contrast, neutrophils added to the endothelial cells in a ratio as low as 2.5:1 caused time-dependent increases in microcarrier staining if pretreated with cytochalasin B (5 .mu.g/mL) before addition with FMLP. Neutrophil cell-free releasate and purified human sputum elastase also caused concentration-related increases in Evans Blue staining of the endothelial-covered microcarriers and these effects were inhibited by the elastase inhibitor methoxysuccinyl-alanyl-prolyl-valyl chloromethyl ketone. This compound also inhibited neutrophil-mediated endothelial permeability increases. The microcarrier-cultured human endothelial monolayer system rapidly detects permeability alterations of endothelial monolayers in response to activated human neutrophils. This model is a potentially useful screening assay for the development of therapeutic agents, directed at neutrophil degranulation or degranulation products, for the control of inflammatory vasopermeability abnormalities.This publication has 28 references indexed in Scilit:
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