title: Intercellular adhesion molecule-1 deficiency protects MRL/MpJ-Fas(lpr) mice from early lethality.
abstract: MRL/MpJ-Fas(lpr) (Fas(lpr)) mice develop a rapidly fatal form of systemic autoimmune disease characterized by glomerulonephritis and vasculitis similar to severe cases of systemic lupus erythematosus in humans. To evaluate the requirement for intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of tissue injury in this model, we created ICAM-1-deficient MRL/MpJ-Fas(lpr) (ICAM-1/Fas(lpr)) mice. ICAM-1 deficiency resulted in a striking improvement in the survival of Fas(lpr) mice (median +/- SEM survival of Fas(lpr) = 26 +/- 1.7 vs ICAM-1/Fas(lpr) = 47 +/- 2.4 wk, p < 0.0001) and the increased survival was associated with delayed elevations of blood urea nitrogen levels in the ICAM-1/Fas(lpr) mice. Histologic examination of the ICAM-1/Fas(lpr) mice revealed an overall reduction in glomerular disease and a significant reduction in vasculitis in the kidney, lung, skin, and salivary glands when compared with Fas(lpr). These findings indicate that ICAM-1 plays a major role in development of glomerular and vascular injury in Fas(lpr) mice.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Bullard
authors.forename: P D
authors.initials: PD
authors.lastname: King
authors.forename: M J
authors.initials: MJ
authors.lastname: Hicks
authors.forename: B
authors.initials: B
authors.lastname: Dupont
authors.forename: A L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: K B
authors.initials: KB
authors.lastname: Elkon
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001327:Autoimmune Diseases / Q000401:mortality*; D005921:Glomerulonephritis / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007678:Kidney Glomerulus / Q000648:ultrastructure; D051379:Mice; D019463:Mice, Inbred MRL lpr; D014657:Vasculitis / Q000517:prevention & control*
chemical_list: D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D018799:Intercellular Adhesion Molecule-1