Differential roles of osteopontin/Eta-1 in early and late lpr disease.
The cytokine osteopontin (Eta-1) leads to macrophage-dependent polyclonal B-cell activation and is induced early in autoimmune prone mice with the lpr mutation, suggesting a significant pathogenic role for this molecule. Indeed, C57BL/6-Fas(lpr/lpr) mice crossed with osteopontin(-/-) mice display delayed onset of polyclonal B-cell activation, as judged by serum immunoglobulin levels. In contrast, they are subject to normal onset, but late exacerbation of lymphoproliferation and evidence of kidney disease. These observations define two stages of Fas(lpr/lpr) disease with respect to osteopontin-dependent pathogenesis that should be taken into account in the design of therapeutic approaches to the clinical disease.
Weber
G F
GF
Department of Cancer Immunology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. gweber@lifespan.org
Cantor
H
H
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008181:Lupus Nephritis / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D009154:Mutation; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics
D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D019014:fas Receptor; D053495:Osteopontin