Schwartz B R, Wayner E A, Carlos T M, Ochs H D, Harlan J M
Department of Medicine, University of Washington, Seattle 98195.
J Clin Invest. 1990 Jun;85(6):2019-22. doi: 10.1172/JCI114668.
Patients with the severe form of leukocyte adhesion deficiency syndrome do not express the CD11/CD18 adhesion complex on any of their leukocytes. Nevertheless, their lymphocytes, unlike their phagocytes, emigrate to extravascular sites of inflammation, demonstrating that surface proteins other than CD11/CD18 can mediate lymphocyte adherence to endothelium. Using a B-lymphoblastoid cell line (B-LCL) established from a CD11/CD18-deficient patient and cultured human umbilical vein endothelial cells (HEC), we investigated the CD11/CD18-independent mechanism(s) of lymphocyte adherence to endothelium. Monoclonal antibodies directed to the alpha 4 polypeptide (CD49d) and the beta 1 polypeptide (CD29) of the lymphocyte VLA-4 integrin receptor (CD49d/CD29), and to vascular cell adhesion molecule-1 (VCAM-1) on the endothelial cell significantly inhibited the adherence of the CD11/CD18-deficient B-LCL to untreated HEC and to HEC treated with recombinant human tumor necrosis factor-alpha. We suggest that the interaction of the lymphocyte receptor VLA-4 with the endothelial ligand VCAM-1 induced by cytokines at sites of inflammation or immune reaction represents a CD11/CD18-independent pathway of lymphocyte emigration.
患有严重形式白细胞黏附缺陷综合征的患者，其任何白细胞上均不表达CD11/CD18黏附复合物。然而，与吞噬细胞不同，他们的淋巴细胞能迁移至血管外的炎症部位，这表明除CD11/CD18之外的表面蛋白也可介导淋巴细胞与内皮细胞的黏附。我们利用从一名CD11/CD18缺陷患者建立的B淋巴母细胞系（B-LCL）和培养的人脐静脉内皮细胞（HEC），研究了淋巴细胞与内皮细胞黏附的不依赖CD11/CD18的机制。针对淋巴细胞VLA-4整合素受体（CD49d/CD29）的α4多肽（CD49d）和β1多肽（CD29）以及内皮细胞上血管细胞黏附分子-1（VCAM-1）的单克隆抗体，可显著抑制CD11/CD18缺陷的B-LCL与未处理的HEC以及经重组人肿瘤坏死因子-α处理的HEC的黏附。我们认为，在炎症或免疫反应部位，细胞因子诱导淋巴细胞受体VLA-4与内皮配体VCAM-1相互作用，代表了一条不依赖CD11/CD18的淋巴细胞迁移途径。
