Platelet-Activating factor receptor blocking reduces proteinuria and improves survival in lupus autoimmune mice

M. Morigi, D. Macconi, E. Riccardi, P. Boccardo, P. Zilio, T. Bertani, G. Remuzzi

Research output: Contribution to journalArticle

Abstract

Platelet-activating factor (PAF) has been suggested recently to play an important role in immune glomerulonephritis, favoring the formation of immune deposits in glomeruli and contributing to the local inflammatory reaction. Here we sought to investigate whether urinary PAF excretion was modified in New Zealand Black x New Zealand White mice a model of genetically determined immune complex disease which mimics systemic lupus in humans and whether changes in PAF urinary excretion values correlated with the extent of proteinuria. To clarify the possible ''in vivo'' relevance of these findings were evaluated whether PAF receptor antagonist has any influence on the evolution of renal disease and survival of these mice. Our results showed that: 1) in lupus mice urinary PAF excretion increased progressively with age in New Zealand Black x White; 2) the increase in PAF excretion correlated with the severity of proteinuria; and 3) the chronic administration of a PAF receptor antagonist {L-659,989 [(±)-trans-2-(3-methoxy-5-methylsulfonyl-4-propoxyphenyl) -5-(3,4,5-trimethoxyphenyl)tetrahydrofuran]} starting from 26 weeks of age significantly delayed the onset of proteinuria and prolonged survival.

Original languageEnglish
Pages (from-to)601-606
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume258
Issue number2
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Pharmacology

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