title: Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells and increase skin vascular permeability.
abstract: Antimicrobial peptides human beta-defensins (hBD) are mainly produced by epithelia of several organs including skin, and participate in innate immunity by killing invading pathogens. Besides their microbicidal activities, hBD activate several inflammatory and immune cells. Since hBD are generated by tissues where mast cells are present, we hypothesized that these peptides could activate mast cells. In this study, we demonstrated that both hBD-3 and hBD-4 induced mast cell degranulation, prostaglandin D2 production, intracellular Ca2+ mobilization and chemotaxis. Furthermore, hBD-3- and hBD-4-induced activation of mast cells was suppressed by pertussis toxin and U-73122, inhibitors for G protein and phospholipase C, respectively. We further revealed that hBD-3 and hBD-4 increased vascular permeability in the skin, which was dependent on the presence of mast cells, because hBD-3 and hBD-4 failed to enhance vascular permeability in mast cell-deficient Ws/Ws rats. We also demonstrated that hBD-3 and hBD-4 induced phosphorylation of MAPK p38 and ERK1/2, which were further required for hBD-mediated mast cell activation, as evidenced by the inhibitory effects of p38 and ERK1/2 inhibitors on mast cell degranulation. Together, these findings suggest the key role of hBD in inflammatory responses by recruiting and activating mast cells, and increasing vascular permeability.
authors.affiliation: Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Chen
authors.forename: François
authors.initials: F
authors.lastname: Niyonsaba
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ushio
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Hara
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yokoi
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
authors.forename: Shigaku
authors.initials: S
authors.lastname: Ikeda
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002199:Capillary Permeability / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000276:immunology*; D010766:Phosphorylation; D051381:Rats; D012867:Skin / Q000098:blood supply / Q000276:immunology*; D023083:beta-Defensins / Q000276:immunology* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D023083:beta-Defensins; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases