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Platelet-activating factor activates two distinct effector pathways in human eosinophils.

Masahiko Kato·Hirokazu Kimura·Youichi Motegi·Atsushi Tachibana·Hisanori Minakami·Akihiro Morikawa·Hirohito Kita
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Abstract

In granulocytes, platelet-activating factor (PAF) shares many of its biological effects with other chemotactic factors, such as FMLP, complement fragments, and lipid mediators. Two unique effects are that PAF is relatively resistant to pertussis toxin (PTX) and that PAF activates the inflammatory functions of eosinophils more strongly than it activates those of neutrophils. To investigate the molecular mechanisms of the responses of eosinophils to PAF, we analyzed superoxide anion production by a chemiluminescence method that provides real-time kinetic data for the cellular responses. We found that PAF induced bimodal superoxide anion production in human eosinophils, consisting of an intense, but transient, first phase and a larger and sustained second phase. In contrast, PAF induced essentially a transient unimodal response in human neutrophils. The two phases of eosinophil response were mediated by distinct cellular mechanisms: the second phase was highly dependent on cellular adhesion and beta(2) integrins, but the first phase was independent of both adhesion and beta(2) integrins. The upstream signaling mechanisms were also different: the second phase was mediated by PTX-resistant G-protein(s) and through activation of phosphatidylinositol 3-kinase, while the first phase was mediated by PTX-sensitive G-protein(s). Furthermore, the second-phase response was approximately 100-fold more resistant to inhibition by a competitive PAF receptor antagonist than the first phase. Thus, eosinophils and neutrophils react differently to PAF, and PAF activates two separate and distinct effector pathways in human eosinophils. These two activation pathways may explain the eosinophils' strong and diverse biological responses to PAF.

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EosinophilsGTP-Binding ProteinsHumansLuminescent MeasurementsNeutrophilsPertussis ToxinPhosphatidylinositol 3-KinasesPlatelet Activating FactorPlatelet Membrane GlycoproteinsReceptors, Cell SurfaceReceptors, G-Protein-CoupledSignal TransductionSuperoxidesComparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Masahiko Kato, Hirokazu Kimura, Youichi Motegi, Atsushi Tachibana, Hisanori Minakami, Akihiro Morikawa, Hirohito Kita. 2002-11-01. Platelet-activating factor activates two distinct effector pathways in human eosinophils.. https://doi.org/10.4049/jimmunol.169.9.5252

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