Enhanced renal leukotriene production in murine lupus

Role of lipoxygenase metabolites

Robert F. Spurney, Phillip Ruiz, David S. Pisetsky, Thomas M. Coffman

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

To investigate the potential role of leukotrienes in murine lupus, we measured renal hemodynamics and renal leukotriene production in MRL-lpr/lpr mice at 12 and 20 weeks of age. Over this age range, these animals develop overt manifestations of autoimmune disease with nephritis similar to human SLE. In the current study, we demonstrated that glomerular filtration rate (GFR) and PAH clearance (CPAH) deteriorated with age in MRL-lpr/lpr mice, but not in MRL-+/+ controls. Impaired renal hemodynamic function in MRL-lpr/lpr mice was associated with enhanced ionophore-stimulated production of both leukotriene B4 (LTB4) and leukotriene C4 (LTC4) by preparations of renal cortex. There was a significant inverse correlation between GFR and in vitro production of both LTC4 and LTB4 in kidneys from MRL-lpr/lpr mice, but not in control animals. In addition, in vitro LTC4 production was correlated with the severity of renal histomorphologic abnormalities. Administration of the specific peptido-leukotriene receptor antagonist SKF104353 to 20 week old MRL-lpr/lpr mice significantly improved both GFR and CPAH, whereas this agent had no effect of renal hemodynamics in MRL-+/+ controls. These results suggest that renal production of LTC4 and LTB4 is increased in MRL-lpr/lpr mice with nephritis, and that enhanced production of peptidoleukotrienes causes reversible renal dysfunction. Increased leukotriene production within the kidney may therefore be important in the pathogenesis of lupus nephritis.

Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalKidney International
Volume39
Issue number1
StatePublished - Jan 1 1991
Externally publishedYes

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Lipoxygenase
Leukotrienes
Kidney
Leukotriene C4
Leukotriene B4
Glomerular Filtration Rate
Nephritis
Hemodynamics
Leukotriene Antagonists
Lupus Nephritis
Ionophores
Autoimmune Diseases

ASJC Scopus subject areas

  • Nephrology

Cite this

Enhanced renal leukotriene production in murine lupus : Role of lipoxygenase metabolites. / Spurney, Robert F.; Ruiz, Phillip; Pisetsky, David S.; Coffman, Thomas M.

In: Kidney International, Vol. 39, No. 1, 01.01.1991, p. 95-102.

Research output: Contribution to journalArticle

Spurney, RF, Ruiz, P, Pisetsky, DS & Coffman, TM 1991, 'Enhanced renal leukotriene production in murine lupus: Role of lipoxygenase metabolites', Kidney International, vol. 39, no. 1, pp. 95-102.
Spurney, Robert F. ; Ruiz, Phillip ; Pisetsky, David S. ; Coffman, Thomas M. / Enhanced renal leukotriene production in murine lupus : Role of lipoxygenase metabolites. In: Kidney International. 1991 ; Vol. 39, No. 1. pp. 95-102.
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