The critical role of intercellular adhesion molecule-1 in masugi nephritis in rats

Jim Wada, Kenichi Shikata, Hirofumi Makino, Shigeru Morioka, Kyoji Hirata, Kosuke Ota, Takuya Tamatani, Masayuki Miyasaka, Tadashi Horiuchi, Sumihare Noji, Kiyoshi Nishikawa, Fumio Myokai, Shigehiko Taniguchi, Yashpal S. Kanwar, Zensuke Ota


21 被引用数 (Scopus)


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.

出版ステータスPublished - 1996

ASJC Scopus subject areas

  • 生理学
  • 腎臓病学
  • 生理学(医学)
  • 泌尿器学


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