Enhancement of renal disease in BXSB lupus prone mice after prior exposure to bacterial lipopolysaccharide.
The mechanism, or mechanisms, responsible for enhancement of renal disease after episodes of infection are poorly understood. We used the BXSB mouse as a lupus model of autoimmune disease and we used bacterial lipopolysaccharide (LPS) as a surrogate infectious agent to gain some insight into the mechanism by which infections promote enhancement of autoimmune disease to chronicity. BXSB mice were exposed to LPS for 5 weeks, LPS was withdrawn and various tests and measurements were performed 6 weeks thereafter. Matched BXSB mice exposed to vehicle injections for 5 weeks served as controls. We verified that previous exposure to LPS enhances polyclonal B cell activation, impairs carrier function of blood cells for immune complexes, increases deposition of immune complexes in the microcirculation and promotes glomerular inflammation and sclerosis. These changes occurred at 6 weeks after withdrawal of LPS in the presence of unimpaired function of mononuclear phagocytes. Some of the effects of LPS are reversible, others are partially so and others are irreversible. Altered immune functions elicited by prior exposure to LPS can result in enhanced involvement of various renal compartments and can result in renal insufficiency.
Granholm
N A
NA
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, OH 45267-0529, USA.
Cavallo
T
T
D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D004198:Disease Susceptibility; D007672:Kidney Cortex / Q000276:immunology / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D010586:Phagocytes / Q000502:physiology; D013997:Time Factors
D000936:Antigen-Antibody Complex; D008070:Lipopolysaccharides