This stud yexamined whether osteopontin (OPN). A molecule with monocyte chemotactis andadhesive activity. Participates in macrophage-m,ediated renal idsease. Accelerated anti-glomerular basement membrane glomerulonephritis was induced in group of six rats. Animalswere treated with a neutralizinganti-OPN or an irrelevant control antibody over days 0-7 (inductionphase) or days 7-14 (established disease). administration of the control antibody had no effect on the severiy of thedisease. In contrast. anti-OPN treatment significantly reducedglomerular injury (urinary protein excretion) and preveted a loss of renal funciton (creatinine clearance) dring the inducion ofdisease. This was accompanied bya significant reduction in renal macrophage and T-cell accumulation. T-cell activaiton. and histologicalinjury (glomerular hypercellularity, segmental lesions. crescents. and tubulointerstitial lesions). An inportan finding was that anti-OPN treatment of established crescentic glomerulonephritis led to a significant reducion in golomerular injury and recovery of renal function in association withinhibition of macrophage and T-cell accumulation. T-cell activation. and histolgical damage. Anti-OPN treatment significantly inhibited the upregulation of OPN and its ligand CD44 but demonstrated no effect on upregulation of intercellular adhesion molecule-1 (ICAM-1) expressionin the kidney. Interestingly. anti-OPN treatment significantly reduced skin swklling and leckocyte infiltration in the delayed type hypersensitivityresponse. However, anti-OPN treatment hadno effect on the humoral immune response. In summary. this study has demonstrate that OPN plays a funcional role in macrophsage and T-cell accumulation and renal damage in both the inducionand progression of a rat model of crescentis glomerulonephritis. thus, OPN may be of pathologcal importance in human glomerulonehphrits and in cellmediated immune diseases generally.