Immune-mediated mesangial cell injury--biosynthesis and function of prostanoids

Kidney Int. 1990 Aug;38(2):273-81. doi: 10.1038/ki.1990.196.

Abstract

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)

MeSH terms

  • Animals
  • Antilymphocyte Serum
  • Complement Activation / immunology
  • Dinoprostone / physiology*
  • Epoprostenol / biosynthesis
  • Glomerular Filtration Rate
  • Glomerular Mesangium / immunology*
  • Glomerulonephritis / immunology*
  • Imidazoles / pharmacology
  • Indomethacin / pharmacology
  • Male
  • Rats
  • Rats, Inbred Lew
  • Rats, Inbred Strains
  • T-Lymphocytes / immunology
  • Thromboxane A2 / biosynthesis
  • Thromboxane B2 / physiology*
  • Thromboxane-A Synthase / antagonists & inhibitors

Substances

  • Antilymphocyte Serum
  • Imidazoles
  • dazmegrel
  • Thromboxane B2
  • Thromboxane A2
  • Epoprostenol
  • Thromboxane-A Synthase
  • Dinoprostone
  • Indomethacin