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Inhibition of Neutrophil‐Dependent Cytotoxicity for Human Endothelial Cells by ACE Inhibitors
Author(s) -
Andersson P.,
Bratt J.,
Heimbürger M.,
Cederholm T.,
Palmblad J.
Publication year - 2014
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12218
Subject(s) - captopril , cytotoxicity , umbilical vein , enalapril , tumor necrosis factor alpha , pharmacology , chemistry , endothelial stem cell , angiotensin converting enzyme , in vitro , immunology , biochemistry , medicine , endocrinology , blood pressure
Angiotensin‐converting enzyme inhibitors ( ACE i) have immunomodulating properties and have been suggested to protect against endothelial injury, for example myocardial infarction and reperfusion injury. We tested whether two ACE i (captopril and enalapril), differing in a thiol group, protected human umbilical vein endothelial cells ( HUVEC ) from cytotoxicity induced by polymorphonuclear neutrophils ( PMN ) in vitro , when cells were activated by tumour necrosis factor‐ α ( TNF α ) or the arachidonate derivative lipoxin‐A 4 ( LXA 4 ), using separate cytotoxicity pathways. When 51 Cr labelled HUVEC were treated with captopril (0–500 μ m ) or enalapril (0–100 μ m ) for 2 h and then activated by TNF α (100 ng/ml) for 24 h, a significant, dose‐dependent reduction of 51 Cr release was observed. Similarly, captopril reduced 51 Cr release when LXA 4 (0.1 μ m ) was used to stimulate PMN for 4 h. Among previously defined mechanisms of significance for the cytotoxic reaction, expression of ICAM ‐1, but not intracellular Ca 2+ changes in PMN or PMN adherence to HUVEC, were reduced by ACE i treatment. Moreover, both ACE i inhibited HUVEC surface expression of TNF α receptor I (but not II ). Thus, these ACE i, particularly captopril, interfere with PMN ‐induced cytotoxicity for endothelial cells by modulating pro‐inflammatory surface receptors, which is a novel effect that might be explored for further therapeutic approaches.