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Macrophages Activated by C-Reactive Protein through FcRI Transfer Suppression of Immune Thrombocytopenia¹

Kristopher D. Marjon^*, Lorraine L. Marnell, Carolyn Mold^* and Terry W. Du Clos^2,*,

^* University of New Mexico and Department of Veterans Affairs Medical Center, Albuquerque, NM 87108

C-reactive protein (CRP) is an acute-phase protein with therapeutic activity in mouse models of systemic lupus erythematosus and other inflammatory and autoimmune diseases. To determine the mechanism by which CRP suppresses immune complex disease, an adoptive transfer system was developed in a model of immune thrombocytopenic purpura (ITP). Injection of 200 µg of CRP 24 h before induction of ITP markedly decreased thrombocytopenia induced by anti-CD41. CRP-treated splenocytes also provided protection from ITP in adoptive transfer. Splenocytes from C57BL/6 mice were treated with 200 µg/ml CRP for 30 min, washed, and injected into mice 24 h before induction of ITP. Injection of 10⁶ CRP-treated splenocytes protected mice from thrombocytopenia, as did i.v. Ig-treated but not BSA-treated splenocytes. The suppressive cell induced by CRP was found to be a macrophage by depletion, enrichment, and the use of purified bone marrow-derived macrophages. The induction of protection by CRP-treated cells was dependent on FcR-chain and Syk activation, indicating an activating effect of CRP on the donor cell. Suppression of ITP by CRP-treated splenocytes required FcRI on the donor cell and FcRIIb in the recipient mice. These findings suggest that CRP generates suppressive macrophages through FcRI, which then act through an FcRIIb-dependent pathway in the recipient to decrease platelet clearance. These results provide insight into the mechanism of CRP regulatory activity in autoimmunity and suggest a potential new therapeutic approach to ITP.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Department of Veterans Affairs and the University of New Mexico Research Allocations Committee.

² Address correspondence and reprint requests to Dr. Terry W. Du Clos, Veterans Administration Medical Center, 1501 San Pedro, S.E., Albuquerque, NM 87108. E-mail address: tduclos{at}unm.edu

³ Abbreviations used in this paper: CRP, C-reactive protein; IC, immune complex; BMM, bone marrow macrophage; Clodronate, dichloromethylene bisphosphonate; ITP, immune thrombocytopenic purpura; IVIg, i.v. Ig.

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