Augmentation of staphylococcal α-toxin signaling by the epidermal platelet-activating factor receptor

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:120

Article

Travers, JB ; Leung, DYM ; Johnson, C ; Schlievert, P ; Marques, M ; Cosgrove, J ; Clay, KL

关键词: arachidonic acid;    calcium;    platelet-activating factor;    staphylococcal alpha-toxin;   

DOI  :  10.1046/j.1523-1747.2003.12149.x

来源: Elsevier

【 摘 要 】

Staphylococcal alpha-toxin is a cytolytic toxin secreted by many strains of Staphylococcus aureus that has proinflammatory and cytotoxic effects on human keratinocytes. alpha-toxin exerts its effects by forming a transmembrane pore that behaves like an ionophore for ions such as calcium. Because cellular membrane disruption with resultant intracellular calcium mobilization is a potent stimulus for the synthesis for the lipid mediator platelet-activating factor, the ability of alpha-toxin to induce platelet-activating factor production was assessed, and whether the epidermal platelet-activating factor receptor could augment toxin-induced signaling in epithelial cells examined. Treatment of the human keratinocyte-derived cell line HaCaT with alpha-toxin resulted in significant levels of platelet-activating factor, which were approximately 50% of the levels induced by calcium ionophore A23187. alpha-toxin also stimulated arachidonic acid release in HaCaT keratinocytes. Pretreatment of HaCaT cells with platelet-activating factor receptor antagonists, or overexpression of the platelet-activating factor metabolizing enzyme acetylhydrolase II blunted alpha-toxin-induced arachidonic acid release by approximately one-third, suggesting a role for toxin-produced platelet-activating factor in this process. Finally, retroviral-mediated expression of the platelet-activating factor receptor into the platelet-activating factor receptor-negative epithelial cell line KB resulted in an augmentation of alpha-toxin-mediated intracellular calcium mobilization and arachidonic acid release. These studies suggest that alpha-toxin-mediated signaling can be augmented via the epidermal platelet-activating factor receptor.

【 授权许可】

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