Role of phospholipase A2 and G-proteins in the IgE-dependent activation of mast cells and macrophages.
The effect of para-bromophenacyl bromide (a selective inhibitor of phospholipase A2) and pertussis toxin has been investigated on IgE-dependent histamine release and on IgE-dependent macrophage-mediated cytotoxicity. Para-bromophenacyl bromide inhibited dose-dependently IgE-dependent stimulation of mast cells and macrophages (IC50's of 5.0 X 10(-7) M and 2.5 X 10(-7) M, respectively). In contrast, pertussis toxin only inhibited the IgE-dependent stimulation of macrophages, whereas the IgE-dependent activation of mast cells was not affected. These results suggest that the transducing mechanisms following the activation of the high affinity receptor for IgE (Fc epsilon RI on mast cells) as well as the low affinity receptor for IgE (Fc epsilon RII on macrophages) induce the activation of phospholipase A2. Fc epsilon RII might be coupled to a pertussis toxin sensitive G-protein.
Laboratoire de Neuroimmunopharmacologie, Université Louis Pasteur-Strasbourg I, Illkirch, France.
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Bronner
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Cothenet
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Monté
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Joseph
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Landry
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Capron
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects; D007073:Immunoglobulin E / Q000276:immunology*; D066298:In Vitro Techniques; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D037342:Pertussis Toxin; D010740:Phospholipases / Q000502:physiology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000098:Acetophenones; D010566:Virulence Factors, Bordetella; D007073:Immunoglobulin E; D037342:Pertussis Toxin; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D019204:GTP-Binding Proteins; C006821:4-bromophenacyl bromide