Enhanced glomerular prostaglandin formation in experimental membranous nephropathy.
To determine whether the induction of immune-mediated glomerular injury influences the formation of cyclooxygenase products by glomerular cells, we determined prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) (as the stable metabolite of TXA2) formation in isolated glomeruli of rats with passive Heymann nephritis (PHN). PHN is a model of membranous nephropathy mediated by antibody and complement independent of inflammatory cells. Five days following induction of PHN by injection of heterologous antibody to rat proximal tubular brush border antigen (Fx1A) rats developed proteinuria 36.5 +/- 34 (controls 3.8 +/- 1 mg/day). Treatment with cobra venom factor, which depleted complement C3 levels to less than 10% of baseline, prevented the development of proteinuria (6.9 +/- 2 mg/day). The development of subepithelial, glomerular immune-complex deposits and proteinuria was associated with a significant stimulation of glomerular PGE2 (87%) and TXB2 (183%) formation. This increment in glomerular prostanoid biosynthesis was significantly inhibited (PGE2 increased 22%, TXB2 increased 75%) in animals that were complement depleted with cobra venom factor. Cobra venom factor had no effect on glomerular prostanoid formation in normal rats. In additional experiments we tested the hypothesis that TXA2 may contribute to mediation of proteinuria in PHN. We utilized a thromboxane synthetase inhibitor UK38485. UK38485 reduced glomerular TXB2 formation by 80% without influencing glomerular deposition of 125I-labeled antibody, and did not alter levels of urine protein excretion in rats with PHN (control 42 +/- 21, UK 38485, 39 +/- 24 mg/day, P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003176:Complement C3 / Q000032:analysis; D015232:Dinoprostone; D005921:Glomerulonephritis / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000096:biosynthesis
D003176:Complement C3; D007093:Imidazoles; D011453:Prostaglandins; D011458:Prostaglandins E; C039242:dazmegrel; D013929:Thromboxane B2; D015232:Dinoprostone