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Circulation. 2003 Nov 11;108(19):2387-92. Epub 2003 Oct 20.

Opposing effects mediated by the chemokine receptor CXCR2 on myocardial ischemia-reperfusion injury: recruitment of potentially damaging neutrophils and direct myocardial protection.

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  • 1Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.

Abstract

BACKGROUND:

The timely reperfusion of ischemic myocardium limits infarction, but components of reperfusion, such as inflammation, may be injurious. The chemokine receptor CXCR2 mediates neutrophil chemotaxis. CXCR2 activation also inhibits hypoxia-induced death of isolated cardiac myocytes. This study assesses whether CXCR2 mediates protection in the intact heart and, if so, the magnitude of this protection relative to CXCR2-mediated chemotaxis of potentially damaging inflammatory cells.

METHODS AND RESULTS:

After ischemia-reperfusion in vivo, CXCR2-/- mice exhibited infarcts that were 50.5% smaller (P<0.05) with 44.3% fewer inflammatory cells (P<0.05) than wild type mice. These data suggest that in this model, CXCR2-mediated chemotaxis may be important in myocardial cell death. To isolate the role of CXCR2 specifically on blood cells, adoptive transfer experiments were performed. After ischemia-reperfusion, infarcts were 53.4% smaller (P<0.05) and contained 65.0% fewer inflammatory cells (P<0.05) in lethally irradiated wild type mice reconstituted with CXCR2-/- compared with wild type bone marrow. Thus, CXCR2 on blood cells is important in myocardial damage, most likely because of CXCR2-mediated chemotaxis. To unmask whether CXCR2 mediates direct myocardial protection in the intact heart, wild type and CXCR2-/- hearts were studied in the absence of blood using Langendorff preparations. In this case, infarcts were 19.7% larger in CXCR2-/- than wild type hearts (P<0.05), revealing a novel CXCR2-mediated cardioprotective effect.

CONCLUSIONS:

CXCR2 exerts opposing effects on myocardial viability during ischemia-reperfusion with recruitment of damaging inflammatory cells predominant over direct tissue protection.

PMID:
14568904
[PubMed - indexed for MEDLINE]
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