Diacylglycerols enhance human neutrophil degranulation responses: relevancy to a multiple mediator hypothesis of cell function.
At 10 microM, 1-0-oleoyl-, 1-0-palmitoyl-, and 1-0-myristoyl-2-0-acetyl-glycerol weakly stimulated neutrophils to release lysozyme, an enzyme in secondary granules, but had no such effect on the release of a primary granule enzyme, beta-glucuronidase. The glycerides (1-10 microM) had a second effect on both granule populations: they enhanced the degranulating potencies of leukotriene B4, platelet-activating factor, a formylated oligopeptide, and C5a by 10- to 30-fold. In contrast, they were much less effective in enhancing responses to ionophore A23187 and partially inhibited responses to phorbol myristate acetate. The diether analogue, 1-0-hexadecyl-2-0-ethylglycerol was inactive in these regards. We suggest that diacylglycerols are a novel class of bioactive products mobilized from phosphoglycerides in stimulated neutrophils; as co-products of this mobilization, platelet-activating factor and leukotriene B4 may interact with diacylglycerols to promote cell function.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000648:ultrastructure*; D004075:Diglycerides / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D005989:Glycerides; D010972:Platelet Activating Factor; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009113:Muramidase; D013755:Tetradecanoylphorbol Acetate