Susceptibility of mast cell-deficient W/Wv mice to pristane-induced experimental lupus nephritis.
In many models of organ-specific autoimmune diseases, mast cells provide a critical cellular link between autoantibodies and end-organ inflammation, both initiating and propagating disease. However, their role in systemic autoimmunity remains speculative. We therefore examined the role of mast cells in a murine model of systemic immune complex-related autoimmune disease, lupus nephritis, expecting to observe the development of humoral autoimmunity in the absence of end-organ disease. Surprisingly, not only did mast cell-deficient animals develop characteristic humoral features of lupus, including hypergammaglobulinemia and autoantibodies, they also developed immune complex glomerulonephritis, as evidenced by renal immune deposits, glomerular disease, and proteinuria. These findings implicate the presence of distinct effector pathways to end-organ damage in humoral autoimmune diseases: one involving the interaction between autoantibodies and mast cells to recruit inflammation in organ-specific autoimmunity, and another involving a more direct--mast cell-independent--interaction between autoantibodies and circulating inflammatory mediators in systemic autoimmunity.
Lin
Ling
L
Department of Internal Medicine/Rheumatology, Washington University School of Medicine, Campus Box 8045, CSRB 6617, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Gerth
Andrea J
AJ
Peng
Stanford L
SL
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006942:Hypergammaglobulinemia / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D008181:Lupus Nephritis / Q000139:chemically induced* / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D013729:Terpenes / Q000494:pharmacology*
D000974:Antibodies, Antinuclear; D007136:Immunoglobulins; D013729:Terpenes; C009042:pristane