Immunopathogenesis of environmentally induced lupus in mice.
Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome defined by clinical and serologic features, including arthritis, glomerulonephritis, and certain autoantibodies such as anti-nuclear ribonucleoprotein (nRNP)/Smith antigen (Sm), DNA, and ribosomal P. Although lupus is considered primarily a genetic disorder, we recently demonstrated the induction of a syndrome strikingly similar to spontaneous lupus in many nonautoimmune strains of mice exposed to the isoprenoid alkane pristane (2,6,10,14-tetramethylpentadecane), a component of mineral oil. Intraperitoneal injection of pristane leads to the formation of lipogranulomas consisting of phagocytic cells that have engulfed the oil and collections of lymphocytes. Subsequently, pristane-treated BALB/c and SJL mice develop autoantibodies characteristic of SLE, including anti-nRNP/Sm, antiribosomal P, anti-Su, antichromatin, anti-single-stranded DNA, and anti-double-stranded DNA. This is accompanied by a severe glomerulonephritis with immune complex deposition, mesangial or mesangiocapillary proliferation, and proteinuria. All inbred mice examined appear to be susceptible to this novel form of chemically induced lupus. Pristane-induced lupus is the only inducible model of autoimmunity associated with the clinical syndrome as well as with the characteristic serologic abnormalities of SLE. Defining the immunopathogenesis of pristane-induced lupus in mice may provide insight into the causes of spontaneous (idiopathic) lupus and also may lead to information concerning possible risks associated with the ingestion or inhalation of mineral oil and exposure to hydrocarbons in the environment.
Shaheen
V M
VM
Division of Rheumatology and Immunology, Departments of Medicine and Microbiology/Immunology, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill 27599-7280, USA.
Satoh
M
M
Richards
H B
HB
Yoshida
H
H
Shaw
M
M
Jennette
J C
JC
Reeves
W H
WH
D000818:Animals; D000936:Antigen-Antibody Complex; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000209:etiology; D004195:Disease Models, Animal; D004781:Environmental Exposure; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology; D006099:Granuloma / Q000209:etiology / Q000473:pathology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D008627:Mercuric Chloride / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D013729:Terpenes / Q000633:toxicity
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D013729:Terpenes; C009042:pristane; D008627:Mercuric Chloride