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β2 integrin-mediated cell-cell contact transfers active myeloperoxidase from neutrophils to endothelial cells

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Item Type:Article
Title:β2 integrin-mediated cell-cell contact transfers active myeloperoxidase from neutrophils to endothelial cells
Creators Name:Jerke, U. and Rolle, S. and Purfürst, B. and Luft, F.C. and Nauseef, W.M. and Kettritz, R.
Abstract:Atherosclerosis and vasculitis both feature inflammation mediated by neutrophil-endothelial-cell (EC) contact. Neutrophil myeloperoxidase (MPO) can disrupt normal EC function, although the mechanism(s) by which MPO is transferred to EC are unknown. We tested the hypothesis that close, beta2-integrin-dependent neutrophil-EC contact mediates MPO transfer from neutrophils to EC. We used sensitive MPO assays and flow cytometry to detect MPO in EC and demonstrate that EC acquired MPO when contacted by neutrophils directly but not when EC and neutrophils were separated in transwells. The transfer was dependent on neutrophil number, exposure time, and incubation temperature. Transfer occurred in several EC types, increased with endotoxin, was not accompanied by MPO release into the medium and was not abrogated by inhibiting degranulation to secretagogues. Confocal microscopy showed MPO internalization by EC with cytoplasmic and nuclear staining. Neutrophils and EC formed intimate contact sites demonstrated by electron microscopy. Blocking CD11b or CD18 beta2-integrin chains, or using neutrophils from CD11b gene-deleted mice, reduced MPO transfer. EC-acquired MPO was enzymatically active, as demonstrated by its ability to oxidize the fluorescent probe aminophenyl fluorescein in the presence of a hydrogen peroxide source. The data suggest an alternative to EC uptake of soluble MPO, namely the cell contact-dependent, {beta}2-integrin-mediated transfer from neutrophils. The findings could be of therapeutic relevance in atherosclerosis and vasculitis.
Keywords:Cell-Cell Interaction, Endothelium, Integrins, Neutrophil, Vascular Biology, Myeloperoxidase, Animals, Mice
Source:Journal of Biological Chemistry
ISSN:0021-9258
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:288
Number:18
Page Range:12910-12919
Date:3 May 2013
Official Publication:https://doi.org/10.1074/jbc.M112.434613
PubMed:View item in PubMed

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