title: Staphylococcus aureus directly activates eosinophils via platelet-activating factor receptor.
abstract: Colonization by SA is associated with exacerbation of AD. Eosinophilic inflammation is a cardinal pathological feature of AD, but little is known about possible direct interaction between SA and eosinophils. PAFR appears to be involved in phagocytosis of Gram-positive bacteria by leukocytes. The objective of this study was to investigate whether SA directly induces eosinophil effector functions via PAFR in the context of AD pathogenesis. Peripheral blood eosinophils were cultured with heat-killed SA, and EDN release, superoxide generation, and adhesion to fibronectin-coated plates were measured. Cytokines, released in the supernatants, were quantified by multiplex bead immunoassays. FISH-labeled SA was incubated with eosinophils and visualized by confocal laser-scanning microscopy. PAFR-blocking peptide and PAFR antagonists were tested for inhibitory effects on SA-induced reactions. SA induced EDN release and superoxide generation by eosinophils in a dose-dependent manner. IL-5 significantly enhanced SA-induced EDN release. IL-5 and IL-17A significantly enhanced SA-induced superoxide generation. SA enhanced eosinophil adhesion to fibronectin, which was blocked by anti-CD49d, and induced eosinophil secretion of various cytokines/chemokines (IL-2R, IL-9, TNFR, IL-1 β, IL-17A, IP-10, TNF-α, PDGF-bb, VEGF, and FGF-basic). After incubation of eosinophils with SA, FISH-labeled SA was visualized in the eosinophils' cytoplasm, indicating phagocytosis. A PAFR-blocking peptide and two PAFR antagonists completely inhibited those reactions. In conclusion, SA directly induced eosinophil activation via PAFR. Blockade of PAFR may be a novel, therapeutic approach for AD colonized by SA.
authors.affiliation: Institute for Clinical Research, Mie National Hospital, Mie, Japan.
authors.forename: Koa
authors.initials: K
authors.lastname: Hosoki
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakamura
authors.forename: Mizuho
authors.initials: M
authors.lastname: Nagao
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hiraguchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tanida
authors.forename: Reiko
authors.initials: R
authors.lastname: Tokuda
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nobori
authors.forename: Shigeru
authors.initials: S
authors.lastname: Suga
authors.forename: Takao
authors.initials: T
authors.lastname: Fujisawa
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013207:Staphylococcal Skin Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor