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Leukotrienes in renal transplant rejection in rats. Distinct roles for leukotriene B4 and peptidoleukotrienes in the pathogenesis of allograft injury.

Publication ,  Journal Article
Spurney, RF; Ibrahim, S; Butterly, D; Klotman, PE; Sanfilippo, F; Coffman, TM
Published in: J Immunol
January 15, 1994

To investigate the role of leukotrienes in renal allograft rejection, we studied the effects of specific leukotriene inhibitors in a rat kidney transplant model. The enhanced renal production of leukotrienes observed in allograft recipients was reduced in a dose-dependent manner by the specific 5-lipoxygenase inhibitor MK886. This suppression of leukotriene production caused a substantial improvement in renal function. Inhibition of 5-lipoxygenase also reduced the severity of vascular inflammation and endothelial injury in allografts, and profoundly inhibited expression of donor MHC class II Ag on kidney cells. Survival of renal allograft recipients was prolonged from 10 +/- 1 days in controls to 16 +/- 1 days in animals that received a 6-day course of MK886 (p < 0.05). To investigate the relative roles of LTB4 compared to peptidoleukotrienes in these processes, we treated a separate group of animals with the specific peptidoleukotriene receptor antagonist SKF106203. This agent inhibits the interaction of peptidoleukotrienes with their receptor(s) but does not affect the biologic actions of LTB4. In these studies, SKF106203 caused a modest improvement in renal allograft function that was of lesser magnitude than that seen with the 5-lipoxygenase inhibitor. SKF106203 also reduced vascular inflammation in allografts, but had no effect on expression of MHC class II Ag. We conclude that leukotrienes play a key role in the pathogenesis of renal allograft rejection. Furthermore, the detrimental effects of leukotrienes in rejection are mediated by distinct actions of LTB4 and peptidoleukotrienes.

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

January 15, 1994

Volume

152

Issue

2

Start / End Page

867 / 876

Location

United States

Related Subject Headings

  • Regional Blood Flow
  • Rats, Inbred Strains
  • Rats
  • Lipoxygenase Inhibitors
  • Leukotriene B4
  • Leukotriene Antagonists
  • Kidney Transplantation
  • Kidney
  • Indoles
  • In Vitro Techniques
 

Citation

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MLA
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Spurney, R. F., Ibrahim, S., Butterly, D., Klotman, P. E., Sanfilippo, F., & Coffman, T. M. (1994). Leukotrienes in renal transplant rejection in rats. Distinct roles for leukotriene B4 and peptidoleukotrienes in the pathogenesis of allograft injury. J Immunol, 152(2), 867–876.
Spurney, R. F., S. Ibrahim, D. Butterly, P. E. Klotman, F. Sanfilippo, and T. M. Coffman. “Leukotrienes in renal transplant rejection in rats. Distinct roles for leukotriene B4 and peptidoleukotrienes in the pathogenesis of allograft injury.J Immunol 152, no. 2 (January 15, 1994): 867–76.
Spurney RF, Ibrahim S, Butterly D, Klotman PE, Sanfilippo F, Coffman TM. Leukotrienes in renal transplant rejection in rats. Distinct roles for leukotriene B4 and peptidoleukotrienes in the pathogenesis of allograft injury. J Immunol. 1994 Jan 15;152(2):867–76.
Spurney RF, Ibrahim S, Butterly D, Klotman PE, Sanfilippo F, Coffman TM. Leukotrienes in renal transplant rejection in rats. Distinct roles for leukotriene B4 and peptidoleukotrienes in the pathogenesis of allograft injury. J Immunol. 1994 Jan 15;152(2):867–876.

Published In

J Immunol

ISSN

0022-1767

Publication Date

January 15, 1994

Volume

152

Issue

2

Start / End Page

867 / 876

Location

United States

Related Subject Headings

  • Regional Blood Flow
  • Rats, Inbred Strains
  • Rats
  • Lipoxygenase Inhibitors
  • Leukotriene B4
  • Leukotriene Antagonists
  • Kidney Transplantation
  • Kidney
  • Indoles
  • In Vitro Techniques