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

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20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)264-272
Number of pages9
JournalNephron
Volume73
Issue number2
DOIs
Publication statusPublished - Jan 1 1996

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Keywords

  • Adhesion molecule
  • Endothelial cell
  • Integrin
  • Intercellular adhesion molecule 1
  • Lymphocyte-function-associated antigen 1
  • Mac-1
  • Masugi nephritis
  • Monocyte
  • Neutrophil

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)
  • Urology

Cite this

Wada, J., Shikata, K., Makino, H., Morioka, S., Hirata, K., Ota, K., Tamatani, T., Miyasaka, M., Horiuchi, T., Noji, S., Nishikawa, K., Myokai, F., Taniguchi, S., Kanwar, Y. S., & Ota, Z. (1996). The critical role of intercellular adhesion molecule-1 in masugi nephritis in rats. Nephron, 73(2), 264-272. https://doi.org/10.1159/000189050