Significance of mononuclear phagocytes in IgA nephropathy

To clarify the significance of mononuclear phagocytes in IgA nephropathy, renal biopsied materials from 45 patients with the disease were examined by the indirect immunoperoxidase method using anti-human monoclonal antibodies and by ultrastructural peroxidase (PO) cytochemistry. The monoclonal antibodies were FMC32, S-100 (alpha), My4, and LeuM5 for detection of mononuclear phagocytes and HLA-DR for Ia antigens. Mesangial hypercellularity in IgA nephropathy was divided into three grades. The number of monocyte/macrophages per glomerulus differed significantly among the grade of mesangial hypercellularity. In the capillary lumen, monocytes were more numerous in the group with slight mesangial hypercellularity. By contrast, macrophages were often found in the Bowman's space and mesangial area of the glomeruli in the advanced group. In the renal interstitium, the number of monocyte/macrophages per 100 interstitial cells differed significantly among the degree of interstitial damage, and they were observed mainly around sclerotic glomeruli. Ultrastructural PO cytochemistry revealed infiltration of monocytes, exudate macrophages, and/or PO-negative macrophages. Clinicopathological study showed a relationship between the number of monocyte/macrophages per glomerulus and the number of glomerular crescents and the degree of proteinuria. The constancy of the percentage of exudate macrophages and polymorphonuclear leukocytes were observed irrespective of the grade of mesangial hypercellularity. On the other hand, the increasing percentage of PO-negative macrophages and decreasing percentage of monocytes were observed over the grade. These results suggest that mononuclear phagocytes might play an important role in the pathogenesis of mesangial hypercellularity, and irreversible glomerular damage and interstitial tissue injury in IgA nephropathy.