Sriramarao P, Norton C R, Borgstrom P, DiScipio R G, Wolitzky B A, Broide D H
La Jolla Institute for Experimental Medicine, CA 92037, USA.
J Immunol. 1996 Nov 15;157(10):4672-80.
The selectin family of adhesion molecules is composed of the L-, E-, and P-selectins, which promote leukocyte rolling during inflammation. Although E-selectin supports neutrophil and lymphocyte rolling, its ability to mediate eosinophil rolling under conditions of flow in vitro and in vivo has not been determined. Using function-blocking mAbs raised against rabbit E-selectin, we have determined whether E-selectin supports human eosinophil rolling in comparison to human neutrophil rolling in IL-1-stimulated rabbit mesenteric venules utilizing intravital microscopy. Anti-rabbit E-selectin mAbs 8B9 and 8G9 were found to inhibit neutrophil rolling but had no significant effect on eosinophil rolling. Likewise, mAb 8B9 F(ab')2 fragments were found to block neutrophil rolling, but did not significantly alter the flux of rolling eosinophils. Isotype-matched Abs and a nonblocking anti-rabbit E-selectin mAb 2A5 failed to inhibit both neutrophil and eosinophil rolling on venular endothelium. In support of these in vivo observations, significant numbers of human neutrophils but not eosinophils were found to avidly roll on monolayers of E-selectin transfectants under physiologic condition of flow in vitro. Under subphysiologic conditions of shear (0.17-0.5 dyn/cm2), eosinophils rolled on E-selectin, albeit in lower numbers (three- to sevenfold) compared with neutrophils. In addition, the rolling velocity of eosinophils was significantly higher compared with neutrophils on E-selectin transfectants. These studies suggest that at physiologic shear rates, E-selectin is likely to function as a major vascular adhesion receptor in mediating neutrophil but not eosinophil rolling in inflamed postcapillary venules.
黏附分子选择素家族由L-选择素、E-选择素和P-选择素组成，它们在炎症过程中促进白细胞滚动。尽管E-选择素支持中性粒细胞和淋巴细胞滚动，但其在体外和体内流动条件下介导嗜酸性粒细胞滚动的能力尚未确定。我们使用针对兔E-选择素产生的功能阻断性单克隆抗体，通过活体显微镜观察，确定在白细胞介素-1刺激的兔肠系膜微静脉中，与人类中性粒细胞滚动相比，E-选择素是否支持人类嗜酸性粒细胞滚动。发现抗兔E-选择素单克隆抗体8B9和8G9可抑制中性粒细胞滚动，但对嗜酸性粒细胞滚动无显著影响。同样，发现单克隆抗体8B9 F(ab')2片段可阻断中性粒细胞滚动，但并未显著改变滚动嗜酸性粒细胞的通量。同型匹配抗体和非阻断性抗兔E-选择素单克隆抗体2A5未能抑制微静脉内皮上的中性粒细胞和嗜酸性粒细胞滚动。为支持这些体内观察结果，发现在体外生理流动条件下，大量人类中性粒细胞而非嗜酸性粒细胞在E-选择素转染细胞单层上快速滚动。在亚生理剪切力条件下（0.17 - 0.5达因/平方厘米），嗜酸性粒细胞在E-选择素上滚动，尽管数量比中性粒细胞少（三到七倍）。此外，与E-选择素转染细胞上的中性粒细胞相比，嗜酸性粒细胞的滚动速度明显更高。这些研究表明，在生理剪切速率下，E-选择素可能作为主要的血管黏附受体，在介导炎症后微静脉中中性粒细胞而非嗜酸性粒细胞滚动方面发挥作用。
