Intasai Nutjeera, Mai Sabine, Kasinrerk Watchara, Tayapiwatana Chatchai
Department of Clinical Microbiology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
Int Immunol. 2006 Jul;18(7):1159-69. doi: 10.1093/intimm/dxl050. Epub 2006 Jun 1.
CD147 is a broadly expressed cell-surface molecule and serves as a signaling receptor for extracellular cyclophilins. CD147 also appears to interact with immune cells, but its counter-receptor on these cells has not been clearly described. In the present report, we displayed multiple copies of the CD147 extracellular domain (CD147Ex) on VCSM13 phage to study the interaction of CD147 with its ligand. Recognition of phage containing fusion protein of CD147Ex and gpVIII (CD147Ex phage) by four different anti-CD147 mAbs indicated that at least parts of the CD147 are properly folded. Specific binding of CD147Ex phage to various cell types was demonstrated by flow cytometry. Morphological changes, however, were observed only in U937, a monocytic cell line, after 24 h incubation with multivalent CD147Ex phage. After 48 h, U937 cell propagation ceased. Staining with annexin V and the presence of cleaved caspase-3 indicated that many of the CD147Ex phage-treated cells had lost viability through apoptotic cell death. The above results suggest that CD147 induces apoptosis in U973 cells and that at least a portion of this cell death program involves a caspase-dependent pathway.
CD147是一种广泛表达的细胞表面分子，作为细胞外亲环素的信号受体。CD147似乎也与免疫细胞相互作用，但其在这些细胞上的反受体尚未明确描述。在本报告中，我们在VCSM13噬菌体上展示了多个CD147细胞外结构域（CD147Ex）拷贝，以研究CD147与其配体的相互作用。四种不同的抗CD147单克隆抗体对含有CD147Ex和gpVIII融合蛋白的噬菌体（CD147Ex噬菌体）的识别表明，至少部分CD147正确折叠。通过流式细胞术证明了CD147Ex噬菌体与各种细胞类型的特异性结合。然而，在用多价CD147Ex噬菌体孵育24小时后，仅在单核细胞系U937中观察到形态学变化。48小时后，U937细胞增殖停止。用膜联蛋白V染色和裂解的半胱天冬酶-3的存在表明，许多经CD147Ex噬菌体处理的细胞通过凋亡性细胞死亡丧失了活力。上述结果表明，CD147诱导U973细胞凋亡，并且该细胞死亡程序的至少一部分涉及半胱天冬酶依赖性途径。
