Published online before print February 28, 2002, doi: 10.1161/01.RES.0000013835.53611.97
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Submitted on November 6, 2001
Revised on February 14, 2002
Accepted on February 14, 2002
Role of 
4 Integrin and VCAM-1 in CD18-Independent Neutrophil Migration Across Mouse Cardiac Endothelium
Robert A. Bowden ;
From the Department of Immunology (R.A.B.), Walter Reed Army Institute of Research, Silver Spring, Md; DeBakey Heart Center at Baylor College of Medicine and Methodist Hospital (Z.-M.D., E.M.D., L.H.M., C.M.B., A.R.B.), Houston, Tex; and the Department of Clinical Studies (T.K.P.), Central Laboratory, Royal Veterinary and Agricultural University, Copenhagen, Denmark.
* To whom correspondence should be addressed. E-mail: aburns{at}bcm.tmc.edu.
Myocardial damage due to reperfusion of ischemic tissue is caused primarily by infiltrating neutrophils. Although leukocyte ß2 integrins (CD18) play a critical role, significant neutrophil emigration persists when CD18 is neutralized or absent. This study examined the role of leukocyte ß1 integrin (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 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.
Key words: neutrophil • myocardium • reperfusion • vascular cell adhesion molecule-1 •
4 integrin
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