Inhibition of monocyte: Endothelial adhesion by oxidized PUFA is reversible and not prevented by antioxidants

S. Sethi, J. W. Eaton

Research output: Contribution to journalArticle

Abstract

Micromolar concentrations of n-3 polyunsaturated fatty acids (PUFA) eicosapentanoic and docosahexanoic acids (present in large amounts in oils of marine fish) will decrease the binding of phagocytes to endothelial surfaces (Sethi et al.. J. Lab. Clin. Med. 128:27, 1996). Our previous observations show that pretreatment of human umbilical vein endothelial cells (HUVEC) with 200 μM n-3 PUFA prior to activation with LPS (50 ng/ ml), IL-1α (10 ng/ml), TNFα (20 ng/ml) or PMA (10 ng/ml) for 5 hrs inhibits subsequent endothelial adhesion of fluorescently labeled monocytic cells (U937). Only oxidized n-3 PUFA are effective and these block not only the induction of VCAM-1 and ELAM-1 (mRNA and product) but also the activation/nuclear translocation of NFκB. Oxidized n-3 PUFA inhibit monocyte adhesion only when added to HUVEC prior to, or at the time of, addition of LPS, IL-1α or TNFα, suggesting that oxidized PUFA inhibit an early event in signal transduction. This inhibition is transient because ≥40 hrs after addition of oxidized PUFA, HUVEC once again respond normally to agonist stimulation. To determine whether antioxidants prevent these effects of oxidized PUFA, HUVEC medium was supplemented with 200 μM butylated hydroxytolidine (BHT) or the Upjohn 'Lazaroid' U74500A (a vitamin E analogue) for varying time periods (1, 6 and 18 hrs) prior to addition of 200 μM oxidized PUFA and LPS stimulation. BHT and U74500A fail to diminish the inhibitory effects of oxidized PUFA on adhesion, indicating that the oxidized PUFA do not act by triggering secondary membrane oxidation. We speculate that this modulation of phagocyte:endothelial adhesion by oxidized lipid may represent a natural mechanism whereby inflammation-mediated oxidation of endogenous PUFA in sites of inflammation may discourage further ingress of phagocytes and, thereby, prevent unrestrained inflammatory responses.

Original languageEnglish (US)
Pages (from-to)A340
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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