Skubitz K M, Campbell K D, Skubitz A P
Department of Medicine, The University of Minnesota Medical School, and Masonic Cancer Center, Minneapolis, 55455, USA.
J Immunol. 1997 Jul 15;159(2):820-8.
The constitutive high expression of CD50 (ICAM-3) on resting leukocytes, coupled with the observation that CD50 is the primary LFA-1 ligand on resting T cells, suggests that CD50 may be an important LFA-1 ligand in the initiation of the immune/inflammatory response. CD50 mAbs have been reported to increase homotypic adhesion of lymphocytes, and lymphocyte adhesion to HUVEC and extracellular matrix proteins. In this study, the effects of CD50 mAbs on neutrophil activation were examined. CD50 mAbs were found to inhibit neutrophil adhesion induced by FMLP and 12-O-tetradecanoyl-phorbol-13-acetate to resting and TNF-activated HUVEC. CD50 mAbs also inhibited neutrophil adhesion stimulated by CD66a, CD66b, CD66c, and CD66d mAbs to HUVEC. CD50 mAbs inhibited the up-regulation of CD11b/CD18 to the neutrophil surface, and the down-regulation of surface CD62L expression. The potential contribution of src family kinases to the previously described tyrosine kinase activity associated with CD50 in neutrophils was also examined. hck and lyn were found to account for much of the tyrosine kinase activity associated with CD50 in neutrophils. The data indicate that CD50 in neutrophils functions not only as a potential ligand for LFA-1, but also regulates the surface expression and activity of CD11b/CD18 and CD62L. In contrast to the effects in lymphocytes, CD50 appears to function as a negative regulator of neutrophil activation.
静息白细胞上CD50（细胞间黏附分子-3）的组成性高表达，以及CD50是静息T细胞上主要的淋巴细胞功能相关抗原-1（LFA-1）配体这一观察结果，提示CD50可能是免疫/炎症反应起始过程中重要的LFA-1配体。据报道，CD50单克隆抗体可增加淋巴细胞的同型黏附，以及淋巴细胞与人类脐静脉内皮细胞（HUVEC）和细胞外基质蛋白的黏附。在本研究中，检测了CD50单克隆抗体对中性粒细胞活化的影响。发现CD50单克隆抗体可抑制N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）和12-O-十四酰佛波醇-13-乙酸酯诱导的中性粒细胞与静息及肿瘤坏死因子（TNF）激活的HUVEC的黏附。CD50单克隆抗体还可抑制CD66a、CD66b、CD66c和CD66d单克隆抗体刺激的中性粒细胞与HUVEC的黏附。CD50单克隆抗体抑制中性粒细胞表面CD11b/CD18的上调以及表面CD62L表达的下调。还检测了src家族激酶对先前描述的与中性粒细胞中CD50相关的酪氨酸激酶活性的潜在贡献。发现hck和lyn在很大程度上介导了中性粒细胞中与CD50相关的酪氨酸激酶活性。数据表明，中性粒细胞中的CD50不仅作为LFA-1的潜在配体发挥作用，还调节CD11b/CD18和CD62L的表面表达及活性。与对淋巴细胞的影响相反,CD50似乎作为中性粒细胞活化的负调节因子发挥作用。
