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

Jeffrey B Travers; Donald Y M Leung; Christopher Johnson; Patrick Schlievert; Mariangela Marques; Jason Cosgrove; Keith L Clay

doi:10.1046/j.1523-1747.2003.12149.x

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

Journal article

Open access

Peer reviewed

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

Jeffrey B Travers, Donald Y M Leung, Christopher Johnson, Patrick Schlievert, Mariangela Marques, Jason Cosgrove and Keith L Clay

Journal of investigative dermatology, Vol.120(5), pp.789-794

05/2003

DOI: 10.1046/j.1523-1747.2003.12149.x

PMID: 12713583

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Abstract

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.

Signal Transduction

Cell Line

Epidermis - metabolism

Arachidonic Acid - metabolism

Calcium - metabolism

Humans

Receptors, G-Protein-Coupled

Receptors, Cell Surface - metabolism

Dose-Response Relationship, Drug

Bacterial Toxins - metabolism

Time Factors

Keratinocytes - metabolism

Platelet Membrane Glycoproteins - metabolism

Epithelial Cells - cytology

Hemolysin Proteins - metabolism

Staphylococcus aureus - metabolism

Details

Title: Subtitle: Augmentation of staphylococcal alpha-toxin signaling by the epidermal platelet-activating factor receptor
Creators: Jeffrey B Travers - Department of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. jtravers@iupui.edu
Donald Y M Leung
Christopher Johnson
Patrick Schlievert
Mariangela Marques
Jason Cosgrove
Keith L Clay
Resource Type: Journal article
Publication Details: Journal of investigative dermatology, Vol.120(5), pp.789-794
Publisher: United States
DOI: 10.1046/j.1523-1747.2003.12149.x
PMID: 12713583
ISSN: 0022-202X
eISSN: 1523-1747
Grant note: HL36577 / NHLBI NIH HHS AR1993 / NIAMS NIH HHS AR41256 / NIAMS NIH HHS HL37260 / NHLBI NIH HHS HL62996 / NHLBI NIH HHS
Language: English
Date published: 05/2003
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984001141702771

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