title: Intercellular adhesion molecule-1, intercellular adhesion molecule-3, and leukocyte integrins in leukocyte accumulation in membranoproliferative glomerulonephritis type I.
abstract: Marked intraglomerular infiltration of leukocytes is observed in membranoproliferative glomerulonephritis (MPGN). We recently demonstrated that this leukocyte infiltration develops partly through macrophage-1 (Mac-1)-positive cells and glomerular C3c deposits (Clin Exp Immunol 100:269-276, 1995). To further investigate the mediation of adhesion molecules in the leukocyte accumulation, we immunohistochemically examined the expression of intraglomerular leukocyte integrins and their ligands as well as surface markers for granulocytes/monocytes (CD15) and macrophages (CD68) in 26 patients with MPGN type I who had undergone repeated biopsies. These patients were divided into two groups. Group A included the patients who showed both normo-complementemia and urinary protein excretion less than 1 g/d at the follow-up biopsy (recovery group: n = 14). Group B (persistent group: n = 12) included the patients other than those in group A. At the initial biopsy, there was no difference in the degree of glomerular C3c deposition, glomerular intercellular adhesion molecule (ICAM)-1 expression, or the numbers of cells bearing leukocyte function-associated antigen-1 (LFA-1), Mac-1, and ICAM-3 between the two groups. At the follow-up biopsy, the degree of glomerular C3c deposition, and the numbers of cells bearing LFA-1, Mac-1, and ICAM-3, were significantly decreased only in group A (P < 0.01, P < 0.001, P < 0.001, and P < 0.01, respectively). No chronological change in ICAM-1 expression was observed in either group. Group B showed a chronological increase in the severity of glomerular injury and serum creatinine level, associated with persistent heavy proteinuria. Neither LFA-1- nor Mac-1-positive cells were positively correlated with ICAM-1 expression. Most of Mac-1-positive cells were CD15-positive cells (granulocytes/monocytes), and a considerable number of Mac-1-positive cells concurrently expressed ICAM-3. In contrast, most LFA-1-positive cells were considered to be CD68-positive cells (macrophages). The number of cells bearing LFA-1 was positively correlated with that of cells bearing ICAM-3 (P < 0.00001). These results suggest that the glomerular leukocytes, infiltrating through Mac-1/complement interaction, express ICAM-3 by themselves, and that LFA-1/ICAM-3 interaction might participate in the glomerular aggregation of leukocytes in MPGN type I. In this study, we could not conclude that LFA-1/ICAM-1 or Mac-1/ICAM-1 interaction was involved in the leukocyte accumulation in this disease.
authors.affiliation: The Second Department of Internal Medicine, Tohoku University School of Medicine, Aoba-ku, Sendai, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Soma
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Ootaka
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Abe
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001706:Biopsy; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D016023:Integrins / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism*; D008297:Male
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1