MONOCYTE SUPEROXIDE GENERATION AND ITS IGA-RECEPTOR IN IGA NEPHROPATHY

Recent studies indicated that polymorphonuclear leukocytes (PMNL) were primed to produce superoxide (O-2(-)) in various types of glomerulone phritis with a particular importance in IgA nephropathy (IgAN). In thi s study, we have examined O-2(-) production and receptor expression fo r the Fc portion of IgA (Fc alpha R) in monocytes to evaluate their in corporation in IgAN, since infiltration of these cells in the glomerul i are more commonly observed than that of PMNL. Similar to PMNL, monoc ytes obtained from IgA nephropathy (IgAN) seemed to be primed both non -specifially and specifically, as increased O-2(-) generation was obse rved to N-formyl methionyl leucyl phenylalanine (FMLP) and phorbol myr istate acetate (PMA), as well as IgA aggregates stimulants, respective ly. Monocytes O-2(-) generation to IgA aggregates was comparatively hi gher in amount than in PMNL, and showed a correlation with the severit y of proteinuria in IgAN patients. Flow cytometric assessment showed a n increased expression of Fc alpha R on circulating monocytes in IgAN patients which showed a linear correlation with the amount of IgA-indu ced O-2(-) generation. Comparing with the previous literature on PMNL, inflammation-related substances such as cytokines/immune complexes, p articularly IgA immune complexes which present in the circulation of I gAN, can prime the phagocytic cells in the circulation for a burst of O-2(-) 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/hem aturia, although it can not be defined as a cause or consequence of th is disease.