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Antibodies to Complement Receptor 3 Treat Established Inflammation in Murine Models of Colitis and a Novel Model of Psoriasiform Dermatitis

Francisco Leon^1,*, Nikhat Contractor^*, Ivan Fuss, Thomas Marth^*, Edward Lahey^*, Shoko Iwaki, Andrea la Sala^*, Victoria Hoffmann, Warren Strober and Brian L. Kelsall^2,*

^* Laboratory of Molecular Immunology, Laboratory of Host Defense, and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Office of Research Services, Division of Veterinary Resources, Office of the Director, National Institutes of Health, Bethesda, MD 20892

Prior studies indicated the ability of Abs to complement receptor 3 (CR3, CD11b/CD18) to suppress the production of IL-12 from immune cells. Therefore, we tested the ability of an anti-CR3 Ab (clone M1/70) to treat established IL-12-dependent Th1-mediated inflammation in murine models. Systemic administration of anti-CR3 significantly ameliorated established intestinal inflammation following the intrarectal administration of trinitrobenzene sulfonic acid (TNBS-colitis), as well as colitis and skin inflammation in C57BL/10 RAG-2^–/– mice reconstituted with CD4⁺CD45RB^high T cells. The hyperproliferative skin inflammation in this novel murine model demonstrated many characteristics of human psoriasis, and was prevented by the adoptive transfer of CD45RB^low T cells. In vitro and in vivo studies suggest that anti-CR3 treatment may act, at least in part, by directly inhibiting IL-12 production by APCs. Administration of anti-CR3 may be a useful therapeutic approach to consider for the treatment of inflammatory bowel disease and psoriasis in humans.

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 Current address: Clinical Discovery/Immunology-Oncology, Pharmaceutical Research Institute, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, NJ 08543.

² Address correspondence and reprint requests to Dr. Brian L. Kelsall, 10/11N113, 10 Center Drive, Bethesda, MD 20892. E-mail address: kelsall{at}nih.gov

³ Abbreviations used in this paper: CR3, complement receptor 3; CM, complete medium; DC, dendritic cell; LPMC, lamina propria mononuclear cell; MPO, myeloperoxidase; PD, psoriasiform dermatitis; RPA, RNase protection assay; SAC, Staphylococcus aureus, Cowan strain 1; TNBS, trinitrobenzene sulfonic acid; WT, wild type.

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