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Inhibition of neutrophil dependent cytotoxicity for human endothelial cells by ACE inhibitors
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.ORCID iD: 0000-0003-3705-0725
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2014 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 80, no 5, 339-345 p.Article in journal (Refereed) Published
Abstract [en]

Angiotensin-converting enzyme inhibitors (ACEi) have immunomodulating properties and have been suggested to protect against endothelial injury, for example myocardial infarction and reperfusion injury. We tested whether two ACEi (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 (TNFα) or the arachidonate derivative lipoxin-A4 (LXA4), using separate cytotoxicity pathways. When 51Cr labelled HUVEC were treated with captopril (0–500 μm) or enalapril (0–100 μm) for 2 h and then activated by TNFα (100 ng/ml) for 24 h, a significant, dose-dependent reduction of 51Cr release was observed. Similarly, captopril reduced 51Cr release when LXA4 (0.1 μm) 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 Ca2+ changes in PMN or PMN adherence to HUVEC, were reduced by ACEi treatment. Moreover, both ACEi inhibited HUVEC surface expression of TNFα receptor I (but not II). Thus, these ACEi, 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.

Place, publisher, year, edition, pages
2014. Vol. 80, no 5, 339-345 p.
National Category
Public Health, Global Health, Social Medicine and Epidemiology
URN: urn:nbn:se:uu:diva-237325DOI: 10.1111/sji.12218ISI: 000343924800005PubMedID: 25124788OAI: oai:DiVA.org:uu-237325DiVA: diva2:767417
Available from: 2014-12-01 Created: 2014-12-01 Last updated: 2014-12-11Bibliographically approved

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