Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines

Article

关键词: HUMAN ENDOTHELIAL-CELLS;    MYOCARDIAL-INFARCTION;    ISCHEMIC-INJURY;    CHEMOATTRACTANT;    IDENTIFICATION;    ADHESION;    RECEPTOR;    INTERLEUKIN-8;    REPERFUSION;    EXPRESSION;   

DOI  :  10.1161/01.CIR.0000148824.93600.F3

来源: SCIE

【 摘 要 】

Background - Angiotensin II (Ang II) is implicated in the development of cardiac ischemic disorders in which prominent neutrophil accumulation occurs. Ang II can be generated intravascularly by the renin-angiotensin system or extravascularly by mast cell chymase. In this study, we characterized the ability of Ang II to induce neutrophil accumulation. Methods and Results - Intraperitoneal administration of Ang II (1 nmol/L) induced significant neutrophil recruitment within 4 hours (13.3 +/- 2.3 x 10(6) neutrophils per rat versus 0.7 +/- 0.5 x 10(6) in control animals), which disappeared by 24 hours. Maximal levels of CXC chemokines were detected 1 hour after Ang II injection (577 +/- 224 pmol/L cytokine-inducible neutrophil chemoattractant [CINC]/keratinocyte-derived chemokine [ KC] versus 5 +/- 3, and 281 +/- 120 pmol/L macrophage inflammatory protein [MIP-2] versus 14 +/- 6). Intravital microscopy within the rat mesenteric microcirculation showed that the short-term (30 to 60 minutes) leukocyte - endothelial cell interactions induced by Ang II were attenuated by an anti-rat CINC/KC antibody and nearly abolished by the CXCR2 antagonist SB-517785-M. In human umbilical vein endothelial cells (HUVECs) or human pulmonary artery media in culture, Ang II induced interleukin (IL)-8 mRNA expression at 1, 4, and 24 hours and the release of IL-8 at 4 hours through interaction with Ang II type 1 receptors. When HUVECs were pretreated with IL-1 for 24 hours to promote IL-8 storage in Weibel-Palade bodies, the Ang II-induced IL-8 release was more rapid and of greater magnitude. Conclusions - Ang II provokes rapid neutrophil recruitment, mediated through the release of CXC chemokines such as CINC/KC and MIP-2 in rats and IL-8 in humans, and may contribute to the infiltration of neutrophils observed in acute myocardial infarction.

【 授权许可】

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