Intercellular adhesion molecule-1 (ICAM-1, CD54), an adhesion molecule of the immunoglobulin superfamily, is an endothelial cell surface ligand for such leukocyte integrins as lymphocyte-function-associated molecule 1 (LFA-1, CD 11 a/CD 18), Mac-1 (CDl lb/CD 18) and CD43. These molecules mediate adhesive interactions between leukocytes and endothelial cells and are critically involved in infiltration of leukocytes into inflammatory lesions. We examined the expression of ICAM-1 in renal tissues of Masugi nephritis rats and directly examined the role of ICAM-1 by administration of neutralizing monoclonal antibodies (MAbs) to rat ICAM-1, LFA-1 α-subunit (LFA-1α), β-subunit (LFA-1β) and Mac-1 α-subunit (Mac-1α). Within 3 h after injection of nephrotoxic serum, increased expression of ICAM-1 was detected in the glomeruli by in situ hybridization and an immunofluorescence study. Protein-uria was significantly suppressed by the MAbs against ICAM-1, Mac-lα and LFA-1β. Neutrophil infiltration into the glomeruli was significantly prevented by injection of the MAbs against ICAM-1, LFA-lα and LFA-1α. These results indicate that both ICAM-l/LFA-1 and ICAM-l/Mac-1 pathways are involved in neutrophil infiltration into the glomeruli. On the other hand, monocytic infiltration was prevented by the MAbs against ICAM-1 LFA-1α and LFA-1β but not by anti-Mac-1 α MAb. Due to these results, ICAM-1 is considered to be a critical molecule involved in the pathogenesis of the leukocyte infiltration into the glomeruli in the heterologous phase of Masugi nephritis. Anti-ICAM-1 antibody may be beneficial in the treatment of leukocyte-mediated glomerular diseases.
- Adhesion molecule
- Endothelial cell
- Intercellular adhesion molecule 1
- Lymphocyte-function-associated antigen 1
- Masugi nephritis
ASJC Scopus subject areas
- Physiology (medical)