BACKGROUND: Platelet-activating factor (PAF) is a potent stimulator of human eosinophils involved in the pathogenesis of allergic diseases. However, intracellular signaling mechanisms in eosinophils involving the PAF receptor are incompletely understood. OBJECTIVE: We sought to determine the roles of protein kinase C (PKC) and cyclic AMP-dependent protein kinase (protein kinase A [PKA]) in signaling pathways of human eosinophils stimulated with PAF. METHODS: After pretreatment with a PKC inhibitor, bisindolylmaleimide I, or a PKA inhibitor, H89, we investigated PAF-evoked functions, such as CD11b expression, cellular adhesion, superoxide anion generation, and degranulation in human eosinophils. RESULTS: Preincubation of eosinophils with bisindolylmaleimide I resulted in enhancement of upregulated CD11b expression and adhesion induced by PAF. H89 pretreatment also enhanced PAF-induced cellular adhesion. Superoxide anion generation and degranulation were suppressed by means of inhibition of either PKC or PKA. CONCLUSION: PKC and PKA negatively regulate PAF-induced CD11b upregulation and cellular adhesion but promote eosinophil effector functions, such as superoxide anion generation and degranulation. PKC and PKA modulate PAF-evoked intracellular signaling of the eosinophil function in distinct ways.
BACKGROUND:Platelet-activating factor (PAF) is a potent stimulator of human eosinophils involved in the pathogenesis of allergic diseases. However, intracellular signaling mechanisms in eosinophils involving the PAF receptor are incompletely understood. OBJECTIVE: We sought to determine the roles of protein kinase C (PKC) and cyclic AMP-dependent protein kinase (protein kinase A [PKA]) in signaling pathways of human eosinophils stimulated with PAF. METHODS: After pretreatment with a PKC inhibitor, bisindolylmaleimide I, or a PKA inhibitor, H89, we investigated PAF-evoked functions, such as CD11b expression, cellular adhesion, superoxide anion generation, and degranulation in human eosinophils. RESULTS: Preincubation of eosinophils with bisindolylmaleimide I resulted in enhancement of upregulated CD11b expression and adhesion induced by PAF. H89 pretreatment also enhanced PAF-induced cellular adhesion. Superoxide anion generation and degranulation were suppressed by means of inhibition of either PKC or PKA. CONCLUSION:PKC and PKA negatively regulate PAF-induced CD11b upregulation and cellular adhesion but promote eosinophil effector functions, such as superoxide anion generation and degranulation. PKC and PKA modulate PAF-evoked intracellular signaling of the eosinophil function in distinct ways.
Authors: Kimberly D Dyer; Caroline M Percopo; Zhihui Xie; Zhao Yang; John Dongil Kim; Francis Davoine; Paige Lacy; Kirk M Druey; Redwan Moqbel; Helene F Rosenberg Journal: J Immunol Date: 2010-04-26 Impact factor: 5.422