Role of α4 integrin and VCAM-1 in CD18-independent neutrophil migration across mouse cardiac endothelium

被引:96
作者
Bowden, RA
Ding, ZM
Donnachie, EM
Petersen, TK
Michael, LH
Ballantyne, CM
Burns, AR
机构
[1] Baylor Coll Med, DeBakey Heart Ctr, Houston, TX 77030 USA
[2] Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD USA
[3] Methodist Hosp, Houston, TX 77030 USA
[4] Royal Vet & Agr Univ, Dept Clin Studies, Cent Lab, Copenhagen, Denmark
关键词
neutrophil; myocardium; reperfusion; vascular cell adhesion molecule-1; alpha(4) integrin;
D O I
10.1161/01.RES.0000013835.53611.97
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
wAbstract-Myocardial damage due to reperfusion of ischemic tissue is caused primarily by infiltrating neutrophils. Although leukocyte beta(2) integrins (CD18) play a critical role, significant neutrophil emigration persists when CD18 is neutralized or absent. This study examined the role of leukocyte g, integrin (alpha(4)) and its endothelial ligand VCAM-1 in CD18-independent neutrophil migration across cardiac endothelium. In a mouse model of myocardial ischemia and reperfusion, we show that compared with wild-type mice, neutrophil infiltration efficiency was reduced by 50% in CD18-null mice; in both types of mice, myocardial VCAM-1 staining increased after reperfusion. In wild-type mice, antibodies against CD18, ICAM-1 (an endothelial ligand for CD18), or VCAM-1 given 30 minutes before ischemia did not block neutrophil emigration at 3 hours reperfusion. Although anti-VCAM-1 attenuated neutrophil emigration by 90% in CD18-null mice, it did not diminish myocardial injury. To determine if CD18-independent neutrophil emigration was a tissue-specific response, we used isolated peripheral blood neutrophils from wild-type or CD18-null mice and showed neutrophil migration across lipopolysaccharide-activated cultured cardiac endothelium is CD18-independent, whereas migration across endothelium obtained from inferior vena cava is CD18-dependent. Consistent with our in vivo findings, migration of CD18-deficient neutrophils on cardiac endothelial monolayers is blocked by antibodies against alpha(4) integrin or VCAM-1. We conclude tissue-specific differences in endothelial cells account, at least partially, for CD18-independent neutrophil infiltration in the heart.
引用
收藏
页码:562 / 569
页数:8
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