Recognition and functional activation of human FcαRI by C-reactive protein (110.22)
| Autor: | Kristopher Marjon, Jinghua Lu, Lorraine Marnell, Ruipeng Wang, Carolyn Mold, Peter Sun, Terry Du Clos |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:110.22-110.22 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | C-Reactive Protein (CRP) is a member of the pentraxin family and an acute phase serum protein. It has been established that CRP and other pentraxins bind FcγRs and induce phagocytosis, activation of signaling, and cytokine synthesis. We report a novel structural and functional interaction between CRP and FcαRI with μM affinity and the binding site for CRP on FcαRI is distinct from that of IgA. Although FcγR and FcαRI bind their immunologlobulin ligands differently, the binding between CRP and FcαRI or FcγRII was inhibited by C1q indicating a similar binding orientation. However, the CRP mutant T173A, which binds poorly to FcγR, showed enhanced binding to FcαRI compared to wild type CRP. CRP crosslinking of FcαRI induced degranulation, ERK phosphorylation and IL-4 production in rat basophilic leukemia cells expressing FcαRI. CRP increased phagocytosis, surface expression of FcαRI, and the production of TNF-α in human neutrophils. The finding that CRP binds to an additional FcR on leukocytes has broad implications for the roles of CRP in host defense, autoimmunity and regulation of the immune response. |
| Databáze: | OpenAIRE |
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