Termeer C, Johannsen H, Braun T, Renkl A, Ahrens T, Denfeld R W, Lappin M B, Weiss J M, Simon J C
Department of Dermatology, University of Freiburg, Germany.
J Leukoc Biol. 2001 Nov;70(5):715-22.
The interaction between CD40 on dendritic cells (DC) and its ligand CD154 has been recognized to be an important feature in the maturation of DC. Here, we were interested in the role of CD44 a surface receptor shown to mediate cell-cell adhesion and binding to Hyaluronic acid (HA). Western blot analysis of human DC stimulated for 3-12 h with CD154 revealed the rapid induction of the 85 kDa standard form of CD44 and an increased HA-binding affinity. Time-lapse video-imaging microscopy of human DC co-cultured on CD154-transfected murine fibroblasts showed that the CD44 up-regulation coincided with the rapid induction of homotypic DC clustering, which did not occur on empty vector-transfected fibroblasts. In this system, addition of anti-CD44s mAbs abrogated DC-cluster formation, thereby inhibiting further maturation, as shown by a reduced TNF-alpha production and inhibition of CD154-induced MHC class II up-regulation. However, co-incubation with HA-degrading enzymes induced no changes in the CD154-mediated DC clustering and maturation.
树突状细胞（DC）表面的CD40与其配体CD154之间的相互作用被认为是DC成熟过程中的一个重要特征。在此，我们关注的是CD44的作用，它是一种表面受体，已证实可介导细胞间黏附并与透明质酸（HA）结合。用CD154刺激人DC 3 - 12小时后的蛋白质免疫印迹分析显示，85 kDa标准形式的CD44被快速诱导，且与HA的结合亲和力增加。在转染了CD154的小鼠成纤维细胞上共培养人DC的延时视频成像显微镜观察显示，CD44的上调与同型DC聚集的快速诱导同时发生，而在转染空载体的成纤维细胞上则未出现这种情况。在该系统中，添加抗CD44s单克隆抗体可消除DC簇的形成，从而抑制进一步成熟，这表现为肿瘤坏死因子-α（TNF-α）产生减少以及CD154诱导的MHC II类分子上调受到抑制。然而，与HA降解酶共同孵育并未引起CD154介导的DC聚集和成熟的变化。
