International Immunology Advance Access originally published online on June 1, 2006
International Immunology 2006 18(7):1159-1169; doi:10.1093/intimm/dxl050
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Binding of multivalent CD147 phage induces apoptosis of U937 cells
1 Department of Clinical Microbiology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand
2 Department of Physiology, Manitoba Institutes of Cell Biology, CancerCare Manitoba, University of Manitoba, Winnipeg R3E 0V9, Canada
3 Division of Clinical Microscopy and
4 Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
5 Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
Correspondence to: C. Tayapiwatana; E-mail: asimi002{at}chiangmai.ac.th and W. Kasinrerk; E-mail: watchara{at}chiangmai.ac.th
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.
Keywords: caspase-3, cell signaling, ligand-receptor interaction, phage display, prokaryotic expression