Broide D H, Humber D, Sullivan S, Sriramarao P
Department of Medicine, University of California, San Diego, CA, USA.
Blood. 1998 Apr 15;91(8):2847-56.
To determine the relative in vivo importance of endothelial expressed adhesion molecules to eosinophil rolling, adhesion, and transmigration, we have induced eosinophilic peritonitis using ragweed allergen in P-selectin-deficient, intracellular adhesion molecule-1 (ICAM-1)-deficient and control wild-type mice. Circulating leukocytes visualized by intravital microscopy exhibited reduced rolling and firm adhesion in P-selectin-deficient mice and reduced firm adhesion in ICAM-1-deficient mice. Eosinophils exhibited reduced rolling and firm adhesion to endothelium in P-selectin-deficient mice. Eosinophil recruitment in P-selectin-deficient mice ( approximately 75% inhibition of eosinophil recruitment) and ICAM-1-deficient mice ( approximately 67% inhibition of eosinophil recruitment) was significantly reduced compared with wild-type mice. Eosinophil recruitment was not completely inhibited in P-selectin/ICAM-1 double-mutant mice (eosinophil recruitment inhibited approximately 62%). However, pretreatment of P-selectin/ICAM-1-deficient mice with an anti-vascular cell adhesion molecule (VCAM) antibody induced near complete inhibition of eosinophil recruitment. Overall, these studies show that eosinophil rolling and firm adhesion is significantly reduced in P-selectin-deficient mice and that P-selectin, ICAM-1, and VCAM are important to eosinophil peritoneal recruitment after ragweed challenge.
为了确定内皮细胞表达的黏附分子对嗜酸性粒细胞滚动、黏附和迁移的相对体内重要性,我们使用豚草过敏原在P-选择素缺陷、细胞间黏附分子-1(ICAM-1)缺陷的小鼠以及对照野生型小鼠中诱导了嗜酸性粒细胞性腹膜炎。通过活体显微镜观察到的循环白细胞在P-选择素缺陷小鼠中滚动和牢固黏附减少,在ICAM-1缺陷小鼠中牢固黏附减少。嗜酸性粒细胞在P-选择素缺陷小鼠中对内皮细胞的滚动和牢固黏附减少。与野生型小鼠相比,P-选择素缺陷小鼠(嗜酸性粒细胞募集抑制约75%)和ICAM-1缺陷小鼠(嗜酸性粒细胞募集抑制约67%)中的嗜酸性粒细胞募集显著减少。嗜酸性粒细胞募集在P-选择素/ICAM-1双突变小鼠中未被完全抑制(嗜酸性粒细胞募集抑制约62%)。然而,用抗血管细胞黏附分子(VCAM)抗体预处理P-选择素/ICAM-1缺陷小鼠可诱导嗜酸性粒细胞募集近乎完全抑制。总体而言,这些研究表明,嗜酸性粒细胞滚动和牢固黏附在P-选择素缺陷小鼠中显著减少,并且P-选择素、ICAM-1和VCAM对豚草激发后嗜酸性粒细胞向腹膜的募集很重要。