The critical role of intercellular adhesion molecule-1 in Masugi nephritis in rats.
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, CD11a/CD18), Mac-1 (CD11b/CD18) 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 alpha-subunit (LFA-1 alpha), beta-subunit (LFA-1 beta) and Mac-1 alpha-subunit (Mac-1 alpha). 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. Proteinuria was significantly suppressed by the MAbs against ICAM-1, Mac-1 alpha and LFA-1 beta. Neutrophil infiltration into the glomeruli was significantly prevented by injection of the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta. These results indicate that both ICAM-1/LFA-1 and ICAM-1/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-1 alpha and LFA-1 beta but not by anti-Mac-1 alpha 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.
Wada
J
J
Third Department of Internal Medicine, Okayama University Medical School, Japan.
Shikata
K
K
Makino
H
H
Morioka
S
S
Hirata
K
K
Ota
K
K
Tamatani
T
T
Miyasaka
M
M
Horiuchi
T
T
Noji
S
S
Nishikawa
K
K
Myokai
F
F
Taniguchi
S
S
Kanwar
Y
Y
Ota
Z
Z
D000818:Animals; D000911:Antibodies, Monoclonal; D019084:Fluorescent Antibody Technique, Indirect; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology*; D007678:Kidney Glomerulus / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1