AGGRAVATION OF RAT NEPHROTOXIC SERUM NEPHRITIS BY ANTIMYELOPEROXIDASEANTIBODIES

To investigate a possible role of anti-neutrophil cytoplasmic antibodi es directed against myeloperoxidase (MPO-ANCA) in glomerulonephritis, we prepared anti-rat MPO antiserum by immunization of rat MPO into a r abbit. Then we administered anti-rat MPO antiserum (group 1) or normal rabbit serum (NRS) (group 2) into rats before injection of nephrotoxi c serum (NTS), which induced nephrotoxic serum nephritis (NTN). Other groups of rats received either anti-rat MPO anti-serum (group 3) or NR S (group 4) before injection of NRS but not NTS. Rats in group 1 and g roup 2 were sacrificed at either 3 hours, 15 hours, or 14 days after N TS injection. Rats in group 3 and group 4 were sacrificed at 15 hours after the last NRS injection. By light microscopy, in rats with NTN sa crificed at 3 hours, counts of polymorphonuclear leukocytes (PMN) per glomerulus were 21.6 +/- 3.5 in group 1 and 8.4 +/- 1.7 in group 2 (P < 0.01). At 15 hours, massive glomerular fibrin deposits were observed in group 1 rats (fibrin score, 131 +/- 8), but not in group 2 rats (f ibrin score, 27 +/- 21; P < 0.01). By direct immunofluorescence micros copy, rat MPO was found along glomerular capillary walls more intensel y in group 1 rats than in group 2 rats. No pathological alterations we re found in group 3 and group 4 rats. Further, renal elution studies r evealed that eluted rabbit IgG contained anti-rat MPO antibodies in gr oup 1 rats but not in group 3 rats. These results suggest that the ant i-MPO antibodies are directly involved in the more severe glomerular l esions in group 1 rats via interactions with MPO itself or activation of PMN, which release various kinds of mediators including MPO.