von Andrian U H, Berger E M, Ramezani L, Chambers J D, Ochs H D, Harlan J M, Paulson J C, Etzioni A, Arfors K E
La Jolla Institute for Experimental Medicine, California 92037.
J Clin Invest. 1993 Jun;91(6):2893-7. doi: 10.1172/JCI116535.
The selectins and the beta 2-integrins (CD11/CD18) mediate distinct adhesive interactions between neutrophils and endothelial cells. Selectins are believed to initiate binding by mediating neutrophil rolling, whereas beta 2-integrins are required for subsequent activation-induced firm sticking and emigration. In vitro evidence suggests that two endothelial cell selectins, P- and E-selectin, can mediate rolling by binding to the carbohydrate ligand sialyl-Lewisx (sLex) on neutrophil surface glycoconjugates. To test the relative contribution of selectins and beta 2-integrins in vivo we used intravital microscopy to study the behavior of neutrophils from two patients with distinct inherited leukocyte adhesion deficiency syndromes. Neutrophils from a patient suffering from CD18 deficiency showed normal rolling behavior but were incapable of sticking or emigrating upon chemotactic stimulation. Neutrophils from a second patient with a newly described adhesion deficiency had normal CD18 but did not express sLex. These neutrophils rolled poorly and also failed to stick in venules under shear force. Under static conditions, however, chemoattractant-induced sticking and emigration could be observed. This demonstrates that both selectin-carbohydrate-mediated initiation of adhesion and subsequent activation-induced beta 2-integrin engagement are essential for the normal function of human neutrophils in vivo.
选择素和β2整合素（CD11/CD18）介导中性粒细胞与内皮细胞之间不同的黏附相互作用。选择素被认为通过介导中性粒细胞滚动来启动结合，而β2整合素则是随后激活诱导的牢固黏附和移出所必需的。体外证据表明，两种内皮细胞选择素，P选择素和E选择素，可通过与中性粒细胞表面糖缀合物上的碳水化合物配体唾液酸化路易斯x（sLex）结合来介导滚动。为了测试选择素和β2整合素在体内的相对作用，我们使用活体显微镜研究了两名患有不同遗传性白细胞黏附缺陷综合征患者的中性粒细胞行为。一名患有CD18缺陷的患者的中性粒细胞表现出正常的滚动行为，但在趋化刺激下无法黏附或移出。另一名患有新描述的黏附缺陷的患者的中性粒细胞具有正常的CD18，但不表达sLex。这些中性粒细胞滚动不佳，在剪切力作用下也无法在小静脉中黏附。然而，在静态条件下，可以观察到趋化因子诱导的黏附和移出。这表明选择素-碳水化合物介导的黏附起始以及随后激活诱导的β2整合素参与对于体内人类中性粒细胞的正常功能至关重要。
