Human CD38 ligand. A 120-KDA protein predominantly expressed on endothelial cells.
Human CD38 ligand. A 120-KDA protein predominantly expressed on endothelial cells.
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人CD38配体。
DOI：
10.4049/jimmunol.156.2.727
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发表时间：
1996
影响因子：
4.4
通讯作者：
F. Malavasi
中科院分区：
文献类型：
--
作者：
S. Deaglio;Umberto Dianzani;Al Horenstein;Juan Fernández;C. Kooten;M. Bragardo;A. Funaro;G. Garbarino;F. Virgilio;J. Banchereau;F. Malavasi
人 CD38 是一种具有 ADP-核糖基环化酶活性的多效性分子，可调节多种细胞类型的活化和生长。其体内功能尚未完全确定，主要是由于缺乏关于单个或多个配体存在的证据。我们最近观察到 CD38 控制淋巴细胞和 HUVEC 之间的选择素型粘附。一组针对 HUVEC 的鼠 mAb 包括一种 (Moon-1)，它不断阻断 CD38 介导的几种细胞系与 HUVEC 的粘附。对大多数正常人体组织的组织分布研究和扩展免疫组织化学分析表明，Moon-1 分子表现出独特的表达模式，在静止和活化的血管内皮、大多数单核细胞、血小板、NK 细胞上高水平存在，在 T、B 和骨髓细胞上也有少量存在。表观分子量为 120 kDa 的 Moon-1 结构被证明是人 CD38 的配体，这是通过在蛋白质印迹实验中使用嵌合小鼠 CD8 α-人 CD38 (mCD8 α-hCD38) 分子作为探针时观察到的直接结合推断的。此外，Ab诱导的调节实验强调了Moon-1分子和人类CD38在共表达这两种结构的细胞系表面上的关联，这两种结构也共享共同的表面表达调节系统。最后，将 Moon-1 直接连接到 T 细胞系上会导致细胞质中钙 ([Ca2+]i) 浓度的相应增加。
Human CD38, a pleiotropic molecule with ADP-ribosyl cyclase activity, regulates activation and growth of several cell types. Its in vivo function is incompletely determined, mainly due to the lack of evidence concerning the existence of a single or multiple ligands. We recently observed that CD38 rules a selectin-type adhesion between lymphoid cells and HUVECs. A panel of murine mAbs raised against HUVEC included one (Moon-1) constantly blocking the CD38-mediated adhesion of several cell lines to HUVEC. Tissue distribution studies and an extended immunohistochemical analysis on the majority of normal human tissues revealed that the Moon-1 molecule displays a unique pattern of expression, being present at high levels on resting and activated vascular endothelium, on the majority of monocytes, platelets, NK cells, and to a lesser extent on T, B, and myeloid cells. The Moon-1 structure of an apparent molecular mass of 120 kDa proved to be a ligand for human CD38, as inferred by the direct binding observed when using a chimeric mouse CD8 alpha-human CD38 (mCD8 alpha-hCD38) molecule as a probe in Western blot experiments. Furthermore, Ab-induced modulation experiments highlighted an association between the Moon-1 molecule and human CD38 on the surface of cell lines coexpressing the two structures, which also share a common regulation system of surface expression. Finally, direct ligation of Moon-1 on T cell lines caused a relevant increase in the cytoplasmic concentration of calcium ([Ca2+]i).