title: Ceramide-CD300f Binding Inhibits Lipopolysaccharide-induced Skin Inflammation.
abstract: LPS triggers inflammatory responses; however, the negative regulation of LPS responsesin vivoremains poorly understood. CD300f is an inhibitory receptor among the CD300 family of paired activating and inhibitory receptors. We have previously identified ceramide as a ligand for CD300f and shown that the binding of ceramide to CD300f inhibits IgE-mediated mast cell activation and allergic responses in mouse models. Here we identify the critical role of CD300f in inhibiting LPS-induced skin inflammation. CD300f deficiency remarkably enhanced LPS-induced skin edema and neutrophil recruitment in mice. Higher levels of factors that increase vascular permeability and of factors that induce neutrophil recruitment were detected in LPS-injected skin pouch exudates ofCD300f-/-mice as compared with wild-type mice. CD300f was highly expressed in mast cells and recruited neutrophils, but not in macrophages, among skin myeloid cells. CD300f deficiency failed to influence the intrinsic migratory ability of neutrophils. Ceramide-CD300f binding suppressed the release of chemical mediators from mast cells and from neutrophils in response to LPS. Adoptive transfer experiments indicated that mast cells mediated enhanced edema in LPS-stimulated skin ofCD300f-/-mice, whereas mast cells together with recruited neutrophils mediated robust neutrophil accumulation. Importantly, administering a ceramide antibody or ceramide-containing vesicles enhanced or suppressed LPS-induced skin inflammation of wild-type mice, respectively. Thus, ceramide-CD300f binding inhibits LPS-induced skin inflammation, implicating CD300f as a negative regulator of Toll-like receptor 4 (TLR4) signalingin vivo.
authors.affiliation: From the Atopy Research Center and.|Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, and.
authors.forename: Emiko
authors.initials: E
authors.lastname: Shiba
authors.affiliation: From the Atopy Research Center and.|the Division of Cellular Therapy/Division of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Izawa
authors.affiliation: From the Atopy Research Center and.|the Division of Cellular Therapy/Division of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kaitani
authors.affiliation: From the Atopy Research Center and.|the Division of Cellular Therapy/Division of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Isobe
authors.affiliation: From the Atopy Research Center and.|the Division of Cellular Therapy/Division of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Akie
authors.initials: A
authors.lastname: Maehara
authors.affiliation: From the Atopy Research Center and.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Uchida
authors.affiliation: From the Atopy Research Center and.
authors.forename: Keiko
authors.initials: K
authors.lastname: Maeda
authors.affiliation: From the Atopy Research Center and.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakano
authors.affiliation: From the Atopy Research Center and.
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: From the Atopy Research Center and.
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.affiliation: the Division of Cellular Therapy/Division of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan kitamura@ims.u-tokyo.ac.jp.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
authors.affiliation: From the Atopy Research Center and.|Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, and.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: From the Atopy Research Center and j-kitaura@juntendo.ac.jp.|the Division of Cellular Therapy/Division of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Kitaura
mesh_terms: D000818:Animals; D002518:Ceramides / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D003872:Dermatitis / Q000276:immunology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*
chemical_list: C482560:CLM-1 protein, mouse; D002518:Ceramides; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic
keywords: inflammation; lipopolysaccharide (LPS); mast cell; neutrophil; receptor