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

Jun 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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 (US)
Pages (from-to)264-272
Number of pages9
JournalNephron
Volume73
Issue number2
DOIs
StatePublished - 1996

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

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