Monocyte superoxide generation and its IgA-receptor in IgA nephropathy

Recent studies indicated that polymorphonuclear leukocytes (PMNL) were primed to produce superoxide (O2-) in various types of glomerulonephritis with a particular importance in IgA nephropathy (IgAN). In this study, we have examined O2- production and receptor expression for the Fc portion of IgA (Fc alpha R) in monocytes to evaluate their incorporation in IgAN, since infiltration of these cells in the glomeruli are more commonly observed than that of PMNL. Similar to PMNL, monocytes obtained from IgA nephropathy (IgAN) seemed to be primed both non-specifically and specifically, as increased O2- generation was observed to N-formyl methionyl leucyl phenylalanine (FMLP) and phorbol myristate acetate (PMA), as well as IgA aggregates stimulants, respectively. Monocytes O2- generation to IgA aggregates was comparatively higher in amount than in PMNL, and showed a correlation with the severity of proteinuria in IgAN patients. Flow cytometric assessment showed an increased expression of Fc alpha R on circulating monocytes in IgAN patients which showed a linear correlation with the amount of IgA-induced O2- generation. Comparing with the previous literature on PMNL, inflammation-related substances such as cytokines/immune complexes, particularly IgA immune complexes which present in the circulation of IgAN, can prime the phagocytic cells in the circulation for a burst of O2- generation to a second stimulus. The increased expression of Fc alpha R appears to be associated with the increase in priming and the degree of priming can be reflected in the severity of proteinuria/hematuria, although it can not be defined as a cause or consequence of this disease.