RGD Reference Report - Platelet-activating factor (PAF) enhances tumor necrosis factor production by alveolar macrophages. Prevention by PAF receptor antagonists and lipoxygenase inhibitors. - Rat Genome Database

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Platelet-activating factor (PAF) enhances tumor necrosis factor production by alveolar macrophages. Prevention by PAF receptor antagonists and lipoxygenase inhibitors.

Authors: Dubois, C  Bissonnette, E  Rola-Pleszczynski, M 
Citation: Dubois C, etal., J Immunol. 1989 Aug 1;143(3):964-70.
RGD ID: 10043183
Pubmed: PMID:2545780   (View Abstract at PubMed)

The effect of platelet-activating factor (PAF) on TNF production by rat alveolar macrophages (AM) and the role of endogenous leukotriene B4 (LTB4) in this regulation were examined. When AM were cultured with PAF alone, no change in TNF production was observed. However, the concomitant addition of PAF and muramyl dipeptide to AM cultures markedly enhanced (2- to 3-fold) TNF production in a concentration-dependent fashion with peak effect at 10(-10)M PAF. This enhancement occurred when muramyl dipeptide and PAF were present together at the initiation of the 24-h culture. Stimulation of TNF production by PAF was blocked by specific, but structurally different PAF receptor antagonists, BN 52021, CV3988 and WEB 2086. Additionally, the stereoisomer of PAF, [S]PAF, and the biologically inactive precursor/metabolite of PAF, lyso-PAF failed to induce significant enhancement in TNF production. In parallel, addition of PAF to AM triggered LTB4 release in a concentration-dependent manner. Inhibition of 5-lipoxygenase by nordihydro-guaiaretic acid or AA-861 blocked the PAF-induced augmentation of both TNF and LTB4 production. This was partially reversed by addition of exogenous LTB4. Collectively, these data suggest that PAF enhances TNF production by interaction with a specific putative receptor and by subsequent induction of endogenous 5-lipoxygenase activity in AM.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of tumor necrosis factor production  IMP 10043183 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptafr  (platelet-activating factor receptor)


Additional Information