INTERCELLULAR-ADHESION MOLECULE-1, INTERCELLULAR-ADHESION MOLECULE-3,AND LEUKOCYTE INTEGRINS IN LEUKOCYTE ACCUMULATION IN MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS TYPE-I

Marked intraglomerular infiltration of leukocytes is observed in membr anoproliferative glomerulonephritis (MPGN). We recently demonstrated t hat this leukocyte infiltration develops partly through macrophage-1 ( Mac-1)-positive cells and glomerular C3c deposits (Clin Exp Immunol 10 0:269-276, 1995). To further investigate the mediation of adhesion mol ecules in the leukocyte accumulation, we immunohistoachemically examin ed the expression of intraglomerular leukocyte integrins and their lig ands as well as surface markers for granulocytes/monocytes (CD15) and macrophages (CD68) in 26 patients with MPGN type I who had undergone r epeated biopsies. These patients were divided into two groups. Group A included the patients who showed both normo-complementemia and urinar y protein excretion less than 1 g/d at the follow-up biopsy (recovery group: n = 14). Group B (persistent group: n = 12) included the patien ts other than those in group A. At the initial biopsy, there was no di fference in the degree of glomerular C3c deposition, glomerular interc ellular adhesion molecule (ICAM)-1 expression, or the numbers of cells bearing leukocyte function-associated antigen-1 (LFA-1), Mac-1, and I CAM-3 between the two groups. At the follow-up biopsy, the degree of g lomerular 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 c hange in ICAM-1 expression was observed in either group. Group B showe d a chronological increase in the severity of glomerular injury and se rum creatinine level, associated with persistent heavy proteinuria. Ne ither LFA-1- nor Mac-1-positive cells were positively correlated with ICAM-1 expression. Most of Mac-1-positive cells were CD15-positive cel ls (granulocytes/monocytes), and a considerable number of Mac-1-positi ve cells concurrently expressed ICAM-3. In contrast, most LFA-1-positi ve cells were considered to be CD68-positive cells (macrophages). The number of cells bearing LFA-1 was positively correlated with that of c ells bearing ICAM-3 (P < 0.00001). These results suggest that the glom erular 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 dise ase. (C) 1996 by the National Kidney Foundation, Inc.