Rebres Robert A, Kajihara Kimberly, Brown Eric J
Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, California, USA.
J Cell Physiol. 2005 Nov;205(2):182-93. doi: 10.1002/jcp.20379.
CD47 is a ubiquitously expressed plasma membrane protein, also known as Integrin Associated Protein, that modulates cell adhesion both through alteration of the avidity of integrin binding and through interaction with its own ligands, the extracellular matrix protein thrombospondin (TSP) and the plasma membrane response regulator SIRPalpha1. We now show that CD47 expression on fibroblasts can induce intercellular adhesion resulting in cell aggregation in the absence of active integrins, SIRPalpha1 binding, and detectable TSP. CD47-expressing cells preferentially bind to other CD47-expressing cells, and intercellular adhesion requires stimulation by serum or a CD47-binding peptide from TSP. Cell-cell adhesion is inhibited by pertussis toxin and C. difficile toxin B, and both adherent and aggregating CD47-expressing fibroblasts have more rac in the GTP bound state than CD47-deficient cells. Spontaneous migration of Jurkat lymphocytes through a fibroblast monolayer is decreased by fibroblast expression of CD47, consistent with an increased barrier function of the CD47 expressing cells. The lymphocyte chemoattractant SDF-1alpha stimulates migration of Jurkat cells through this monolayer only if both the lymphocytes and fibroblasts express CD47, and the inhibition of migration by a CD47-interacting peptide from TSP similarly requires CD47 expression on both cell types. Thus, signaling dependent on both heterotrimeric and rho family GTPases can induce CD47 to participate in cell-cell interactions independent of known ligands that enhance intercellular adhesion and modulate cell migration.
CD47是一种广泛表达的质膜蛋白，也被称为整合素相关蛋白，它通过改变整合素结合的亲和力以及与自身配体（细胞外基质蛋白血小板反应蛋白（TSP）和质膜反应调节因子SIRPα1）相互作用来调节细胞黏附。我们现在表明，成纤维细胞上的CD47表达可在没有活性整合素、SIRPα1结合和可检测到的TSP的情况下诱导细胞间黏附，导致细胞聚集。表达CD47的细胞优先与其他表达CD47的细胞结合，细胞间黏附需要血清或来自TSP的CD47结合肽的刺激。细胞间黏附受到百日咳毒素和艰难梭菌毒素B的抑制，并且黏附的和聚集的表达CD47的成纤维细胞比缺乏CD47的细胞具有更多处于GTP结合状态的rac。Jurkat淋巴细胞通过成纤维细胞单层的自发迁移因成纤维细胞表达CD47而减少，这与表达CD47的细胞屏障功能增强一致。淋巴细胞趋化因子SDF-1α仅在淋巴细胞和成纤维细胞都表达CD47时才刺激Jurkat细胞通过该单层迁移，并且来自TSP的与CD47相互作用的肽对迁移的抑制同样需要两种细胞类型都表达CD47。因此，依赖于异源三聚体和rho家族GTP酶的信号传导可诱导CD47参与细胞间相互作用，而不依赖于增强细胞间黏附并调节细胞迁移的已知配体。
