Deaglio S, Morra M, Mallone R, Ausiello C M, Prager E, Garbarino G, Dianzani U, Stockinger H, Malavasi F
Dipartimento di Genetica, Biologia e Chimica Medica, Università di Torino, Italy.
J Immunol. 1998 Jan 1;160(1):395-402.
Human CD38 is a cell surface molecule involved in the regulation of lymphocyte adhesion to endothelial cells. This suggests that HUVEC bear a ligand(s) for CD38 on the cell surface. By means of the mAb Moon-1, which specifically inhibits CD38-mediated cell adhesion, we have identified a trans-membrane 130-kDa molecule acting as a ligand for CD38. Here, we report that the molecule recognized by the Moon-1 mAb is CD31, a member of the Ig superfamily. This conclusion is based on 1) cross-inhibition assays between Moon-1 and reference anti-CD31 mAbs; 2) sequential immunoprecipitation experiments using Moon-1 and known anti-CD31 mAbs, and 3) reactivity of the Moon-1 mAb with CD31 transfectants. Further, CD31 and CD38 cognate interactions were found to modulate heterotypic adhesion as well as to implement cytoplasmic calcium fluxes identical to those obtained by means of agonistic anti-CD38 mAbs. Other effects tested included the synthesis of messages for a panel of cytokines, markedly increased upon receptor-ligand interactions. These results suggest that the interplay between CD38 and its ligand CD31 is an important step in the regulation of cell life and of the migration of leukocytes (and CD38+ cancer cells) through the endothelial cell wall.
人类CD38是一种参与调节淋巴细胞与内皮细胞黏附的细胞表面分子。这表明人脐静脉内皮细胞（HUVEC）在细胞表面带有CD38的一种配体。借助特异性抑制CD38介导的细胞黏附的单克隆抗体（mAb）Moon-1，我们鉴定出一种130 kDa的跨膜分子作为CD38的配体。在此，我们报告Moon-1 mAb识别的分子是CD31，它是免疫球蛋白超家族的成员。这一结论基于以下几点：1）Moon-1与参考抗CD31 mAb之间的交叉抑制试验；2）使用Moon-1和已知抗CD31 mAb进行的连续免疫沉淀实验；3）Moon-1 mAb与CD31转染细胞的反应性。此外，发现CD31和CD38的同源相互作用可调节异型黏附，并产生与通过激动性抗CD38 mAb获得的相同的细胞质钙通量。测试的其他效应包括一组细胞因子的信使合成，在受体-配体相互作用时显著增加。这些结果表明，CD38与其配体CD31之间的相互作用是调节细胞生命以及白细胞（和CD38+癌细胞）通过内皮细胞壁迁移的重要步骤。
