Immune-mediated mesangial cell injury--biosynthesis and function of prostanoids.
We studied the formation of cyclo-oxygenase products in a rat model of mesangial cell injury, in order to determine a possible role of prostaglandin E2 (PGE2), prostaglandin I2 (determined as 6-keto-PGF1 alpha and thromboxane A2 (TxA2) in immune-mediated glomerular disease. Selective immune-mediated mesangial cell injury was induced by i.v. administration of a rabbit anti-rat thymocyte antiserum (ATS). Intravenous ATS leads to immune deposits in the mesangium followed by mesangiolysis and the infiltration of polymorphonuclear granulocytes and monocytes. Glomerular TxB2 formation two hours (292 +/- 27 pg/mg/min) and 48 hours (396 +/- 69 pg/mg/min) following antibody was significantly (P less than 0.05) higher compared to animals receiving non-antibody rabbit IgG (TxB2: 2 hr 143 +/- 13; 48 hr 171 +/- 32 pg/mg/min). Treatment with cobra venom factor (CVF) and the reduction of glomerular monocyte infiltration inhibited the increase of glomerular TxB2 formation significantly. Depletion of granulocytes with a rabbit anti-rat granulocyte serum had no effect on glomerular prostanoid formation following ATS. Glomerular PGE2 and 6-keto PGF1 alpha production was not altered following ATS. Inulin clearance in rats with immune-mediated mesangial cell injury was significantly (P less than 0.001) lower at two hours (456 +/- 24 microliters/min/100 g body wt) and 48 hours (433 +/- 54 microliters/min/100 g body wt) compared to their corresponding control animals which were treated with non-antibody IgG (2 hr: 914 +/- 51; 48 hr: 694 +/- 79 microliters/min/100 g body wt).(ABSTRACT TRUNCATED AT 250 WORDS)
Stahl
R A
RA
Department of Medicine, University of Frankfurt am Main, Federal Republic of Germany.
Thaiss
F
F
Kahf
S
S
Schoeppe
W
W
Helmchen
U M
UM
D000818:Animals; D000961:Antilymphocyte Serum; D003167:Complement Activation / Q000276:immunology; D015232:Dinoprostone / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis; D005919:Glomerular Filtration Rate; D005920:Glomerular Mesangium / Q000276:immunology*; D005921:Glomerulonephritis / Q000276:immunology*; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D000961:Antilymphocyte Serum; D007093:Imidazoles; C039242:dazmegrel; D013929:Thromboxane B2; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D015232:Dinoprostone; D007213:Indomethacin