Importance of E-selectin for firm leukocyte adhesion in vivo

被引:145
作者
Ley, K
Allietta, M
Bullard, DC
Morgan, S
机构
[1] Univ Virginia, Hlth Sci Ctr, Sch Med, Dept Biomed Engn, Charlottesville, VA 22908 USA
[2] Univ Alabama, Dept Comparat Med, Birmingham, AL 35294 USA
关键词
D O I
10.1161/01.RES.83.3.287
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Leukocyte adhesion under flow is preferentially mediated by the selectins. In this study we used intravital microscopy to investigate whether E-selectin may promote firm leukocyte adhesion in vivo, E-Selectin is expressed by endothelial cells activated with tumor necrosis factor-ct (TNF-ct) and causes slow leukocyte rolling. Microinjection of formyl-methionyl-leucyl-phenylalanine (fMLP) or macrophage inflammatory protein-2 (MIP-2) next to a venule of the TNF-alpha-treated mouse cremaster muscle significantly increased the number of adherent leukocytes. In gene-targeted mice homozygous for a null mutation in the E-selectin gene or in wild-type mice treated with an E-selectin monoclonal antibody (mAb), this response was significantly attenuated (by >80%). No such defect was seen in intercellular adhesion molecule-1 (ICAM-1)-deficient mice. E-Selectin-null mice showed more rapid leukocyte rolling than wild-type or ICAM-1-deficient mice, resulting in significantly shortened leukocyte transit times through venules. Topical application of fMLP onto the whole cremaster muscle generated the same number of adherent leukocytes in wild-type and E-selectin-deficient mice. We conclude that slow leukocyte rolling through E-selectin results in long transit times, which are essential for efficient leukocyte adhesion in response to a local chemotactic stimulus.
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页码:287 / 294
页数:8
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