Bacterial lipopolysaccharide priming of P388D1 macrophage-like cells for enhanced arachidonic acid metabolism. Platelet-activating factor receptor activation and regulation of phospholipase A2

K. B. Glaser, R. Asmis, E. A. Dennis

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P388D1 cells are stimulated by platelet-activating factor (PAF) to release arachidonic acid metabolites (Lister, M.D., Glaser, K.B., Ulevitch, R.J., and Dennis, E.A. (1989) J. Biol. Chem. 264, 8520-8528). While the release of prostaglandin E2 (PGE2) in response to PAF is only two to three times the constitutive PGE2 production, bacterial lipopolysaccharides (LPS) are able to prime P388D1 cells for enhanced arachidonic metabolism, increasing PAF-stimulating PGE2 production to 9-12 times the constitutive PGE2 production. The extent and rate of [3H]arachidonic acid release from prelabeled P388D1 cells are also increased in primed cells relative to unprimed cells in response to PAF-stimulation. LPS from either Salmonella Re595 or Escherichia coli 0111:B4 prime P388D1 cells in a concentration-dependent manner but have themselves no ability to stimulate arachidonic acid metabolism. LPS priming is sensitive to inhibition by actinomycin D, while primed PAF-stimulation of PGE2 production is blocked by cyclohexamide which implicates a protein which is rapidly turning over. Primed PAF stimulation is also inhibited by the phospholipase A2 inhibitor manoalogue and the tyrosine-specific protein kinase inhibitor genistein, but not by the kinase inhibitor H-7. These results suggest that priming amplifies signal transduction pathways for PAF, which results in increased arachidonate availability. The multiple levels at which primed PAF-stimulated PGE2 production appears to be regulated are discussed.

Original languageEnglish (US)
Pages (from-to)8658-8664
Number of pages7
JournalJournal of Biological Chemistry
Issue number15
StatePublished - Jun 12 1990


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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