| Abstract: |
MRL/MpJ-Faslpr (Faslpr) 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-Faslpr (ICAM-1/Faslpr) mice. ICAM-1 deficiency resulted in a striking improvement in the survival of Faslpr mice (median ± SEM survival of Faslpr = 26 ± 1.7 vs ICAM-1/Faslpr = 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/Faslpr mice. Histologic examination of the ICAM-1/Faslpr 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 Faslpr. These findings indicate that ICAM-1 plays a major role in development of glomerular and vascular injury in Faslpr mice. |
