Horenstein A L, Stockinger H, Imhof B A, Malavasi F
Laboratory of Cell Biology, Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 19, 10126 Torino, Italy.
Biochem J. 1998 Mar 15;330 ( Pt 3)(Pt 3):1129-35. doi: 10.1042/bj3301129.
Soluble forms of membrane receptors are emerging candidates as physiological regulators of leukocyte trafficking. In the present study, we found that the soluble form of the CD38 antigen (sCD38) bears a binding domain of low affinity for a cellular receptor on U937 cells. Cross-linking and peptide-mapping studies confirmed the physical association and the identification of the U937 receptor as a 130 kDa protein. The binding of sCD38 to the receptor was differentially inhibited by several monoclonal antibodies against the CD31 cell-adhesion molecule. Thus the interaction was analysed through direct association of soluble and membrane CD38 with soluble recombinant murine CD31 with three N-terminal and with all six extracellular Ig domains. Cross-linking experiments on U937 intact cells, and ligand blot assays of the immunoprecipitated CD38 molecule, indicated that (i) the recognized epitope is determined by the tertiary structure of the molecule, and that (ii) the binding domain involved resides in the ectocellular portion of the CD31 molecule, more precisely in the first three N-terminal domains. A comparative functional activity between murine and human CD31 was also explored. The data presented suggest that (i) human CD31 bears a highly functional similarity with its murine counterpart, as it is a receptor in myeloid cells with more than one ligand (the alphavbeta3 integrin and the CD38 molecule), and that (ii) the activity of sCD38 as decoy molecule for CD31 may play an important role in cell-cell interactions in physiological and pathological conditions.
可溶性膜受体正逐渐成为白细胞迁移的生理调节因子的候选物质。在本研究中，我们发现CD38抗原的可溶性形式（sCD38）对U937细胞上的一种细胞受体具有低亲和力结合域。交联和肽图谱研究证实了这种物理关联，并鉴定出U937受体是一种130 kDa的蛋白质。sCD38与该受体的结合受到几种抗CD31细胞粘附分子单克隆抗体的差异抑制。因此，通过可溶性和膜结合型CD38与具有三个N端和所有六个细胞外免疫球蛋白结构域的可溶性重组鼠CD31的直接结合来分析这种相互作用。对U937完整细胞进行的交联实验以及免疫沉淀的CD38分子的配体印迹分析表明：（i）识别的表位由分子的三级结构决定，且（ii）涉及的结合域位于CD31分子的胞外部分，更确切地说是在前三个N端结构域。还探索了鼠和人CD31之间的比较功能活性。所呈现的数据表明：（i）人CD31与其鼠对应物具有高度的功能相似性，因为它是髓系细胞中的一种受体，具有不止一种配体（αvβ3整合素和CD38分子），且（ii）sCD38作为CD31的诱饵分子的活性可能在生理和病理条件下的细胞间相互作用中发挥重要作用。
