Differences in glomerular leukocyte infiltration between IgA nephropathy and membranoproliferative glomerulonephritis

Background. An important aspect in glomerular nephritic processes is the enhanced influx of leukocytes into the glomerulus. Methods. To investigate the mechanisms of intraglomerular leukocyte infiltration in IgA nephropathy (IgA-N) and membranoproliferative glomerulonephritis type I (MPGN-I), we immunohistochemically examined the intraglomerular expression of leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18), macrophage-1 (Mac-1, CD11b/CD18) and intercellular adhesion molecule-1 (ICAM-1, CD54) together with glomerular deposition of C3c and fibrinogen. Results. In IgA-N (n = 42), LFA-1⁺ cells were distributed mainly in glomeruli with intense expression of ICAM-1, and there was a positive correlation (P < 0.001) between the number of LFA-1⁺ cells and the degree of ICAM-1 expression. Mac-1⁺ cells had no correlation with glomerular C3c deposition, but had a significant correlation with fibrinogen deposition (P < 0.05). The number of LFA-1⁺ cells was significantly greater than of Mac-1⁺ cells (P < 0.05). The number of LFA-1⁺ cells was strongly correlated with that of CD68⁺ cells (P < 0.00001). In MPGN-I n = 43), on the contrary, Mac-1⁺ cells correlated only with C3c deposition (P < 0.001), and they were observed mainly in peripheral loops of glomerular capillaries where C3c was deposited with a similar distribution. However, there was no relationship between LFA-1⁺ cells and ICAM-I expression. The number of Mac-1⁺ cells was greater than that of LFA-1⁺ cells (P < 0.0001), and most Mac-1⁺ cells were identical to CD15⁺ cells. Conclusion. These results indicate the possibility that different mechanisms may cause glomerular leukocyte infiltration in various forms of human glomerulonephritis. The LFA-1/ICAM-1 pathway may play an important role in glomerular leukocyte infiltration in IgA-N, while the Mac-1/complement pathway may be important in MPGN-I. The former may promote mainly the infiltration of CD68⁺ cells, and the latter may promote that of CD15⁺ cells. In addition, Mac-1⁺ cells may act as fibrinogen and complement receptors in IgA-N and MPGN-I, respectively.