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Binding of multivalent CD147 phage induces apoptosis of U937 cells
Nutjeera Intasai1, Sabine Mai, Watchara Kasinrerk
1Department of Clinical Microbiology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.
Abstract:
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.
Insights
CD147 (Cluster of Differentiation 147) on immune cells can trigger apoptosis. This study used phage display to show CD147Ex phage induced cell death in U937 monocytic cells via a caspase-dependent pathway.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- CD147 is a cell-surface molecule involved in signaling with extracellular cyclophilins.
- Its interaction with immune cells is known, but the specific counter-receptor remains unidentified.
- Understanding CD147's role in immune cell function is crucial.
Purpose of the Study:
- To investigate the interaction of CD147 with its ligands on immune cells.
- To determine if CD147 can induce cellular responses, specifically apoptosis, in immune cells.
- To elucidate the pathway involved in CD147-mediated cell death.
Main Methods:
- Engineered VCSM13 phage to display multiple copies of the CD147 extracellular domain (CD147Ex).
- Utilized flow cytometry to assess the binding of CD147Ex phage to various cell types.
- Analyzed morphological changes, cell proliferation, and apoptotic markers (annexin V, cleaved caspase-3) in U937 cells upon phage treatment.
Main Results:
- CD147Ex phage specifically bound to various cell types, including U937 monocytic cells.
- Incubation with multivalent CD147Ex phage induced morphological changes and cessation of U937 cell propagation.
- Treated U937 cells exhibited significant apoptotic cell death, confirmed by annexin V staining and cleaved caspase-3 presence.
Conclusions:
- CD147 plays a role in inducing apoptosis in U937 monocytic cells.
- The observed CD147-mediated apoptosis involves a caspase-dependent pathway.
- This study provides insights into CD147's function in immune cell regulation and programmed cell death.
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