2-STEP MODEL OF LEUKOCYTE ENDOTHELIAL-CELL INTERACTION IN INFLAMMATION - DISTINCT ROLES FOR LECAM-1 AND THE LEUKOCYTE BETA-2 INTEGRINS INVIVO
2-STEP MODEL OF LEUKOCYTE ENDOTHELIAL-CELL INTERACTION IN INFLAMMATION - DISTINCT ROLES FOR LECAM-1 AND THE LEUKOCYTE BETA-2 INTEGRINS INVIVO
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DOI：
10.1073/pnas.88.17.7538
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发表时间：
1991-09-01
影响因子：
11.1
通讯作者：
BUTCHER, EC
中科院分区：
文献类型：
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作者：
VONANDRIAN, UH;CHAMBERS, JD;BUTCHER, EC
凝集素归巢受体LECAM-1(LAM-1，Leu8)和β-2整合素，特别是Mac-I(CD11b/CD18)参与了炎症中白细胞与内皮细胞的相互作用。当中性粒细胞激活时，LECAM-1迅速脱落，而Mac-I的表达显著增加，这表明这些分子在功能上具有不同的作用。利用活体视频显微镜，我们比较了抗LECAM-1和CD18抗体对白细胞与兔肠系膜小静脉相互作用的影响。抗LECAM-1单抗及其Fab片段可抑制最初可逆的白细胞沿血管壁滚动。抗CD18单抗对静脉内皮细胞的滚动无影响，但可阻止白细胞与静脉内皮细胞的牢固附着。这些结果支持白细胞-内皮细胞相互作用的两步模型：部分由LECAM-1介导的可逆滚动促进局部微环境对白细胞的招募，并先于涉及β-2整合素的激活依赖的牢固附着。
The lectin homing receptor LECAM-1 (LAM-1, Leu8) and the beta-2 integrins, particularly Mac-I (CD11b/CD18), participate in leukocyte-endothelial cell interactions in inflammation. LECAM-1 is rapidly shed while Mac-I expression is dramatically increased upon neutrophil activation, suggesting functionally distinct roles for these molecules. Using intravital video microscopy, we have compared the effect of antibodies against LECAM-1 and CD18 on leukocyte interactions with rabbit mesenteric venules. Anti-LECAM-1 monoclonal antibody and its Fab fragments inhibited initial reversible leukocyte rolling along the vascular wall. Anti-CD18 monoclonal antibody had no effect on rolling but prevented subsequent firm attachment of leukocytes to venular endothelium. These results support a two-step model of leukocyte-endothelial cell interactions: reversible rolling mediated in part by LECAM-1 facilitates leukocyte recruitment by the local microenvironment and precedes activation-dependent firm attachment involving beta-2 integrins.