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* Integrated Program in Cellular, Molecular, and Biophysical Studies,
Department of Microbiology and Medicine,
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10032; and
Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104
Lupus glomerulonephritis is initiated by deposition of IgG-containing immune complexes in renal glomeruli. FcR engagement by immune complexes (IC) is crucial to disease development as uncoupling this pathway in FcR
–/– abrogates inflammatory responses in (NZB x NZW)F1 mice. To define the roles of FcR-bearing hemopoietic cells and of kidney resident mesangial cells in pathogenesis, (NZB x NZW)F1 bone marrow chimeras were generated. Nephritis developed in (NZB x NZW)F1 mice expressing activating FcRs in hemopoietic cells. Conversely, recipients of FcR–/– bone marrow were protected from disease development despite persistent expression of FcR in mesangial cell populations. Thus, activating FcRs on circulating hemopoietic cells, rather than on mesangial cells, are required for IC-mediated pathogenesis in (NZB x NZW)F1. Transgenic FcR–/– mice expressing FcR limited to the CD11b+ monocyte/macrophage compartment developed glomerulonephritis in the anti-glomerular basement disease model, whereas nontransgenic FcR–/– mice were completely protected. Thus, direct activation of circulating FcR-bearing myeloid cells, including monocytes/macrophages, by glomerular IC deposits is sufficient to initiate inflammatory responses.
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 Immunology Training Program (T32 AI 07525 (to A.B.), the National Institutes of Health/National Institute of Allergy and Infectious Diseases RO3AR45764, and by an Investigator Award of the Arthritis Foundation (to R.C.).
2 Address correspondence and reprint requests to Dr. Raphael Clynes, Columbia University, College of Physicians and Surgeons, P & S Building, Room 8-510, 630 West 168th Street, New York, NY 10032. E-mail address: rc645{at}columbia.edu
3 Abbreviations used in this paper: IC, immune complex; MC, mesangial cell; GBM, glomerular basement membrane; WT, wild type; BM, bone marrow; PAS, periodic acid-Schiff; SLE, systemic lupus erythematosus.
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