title: Role of Ceramide from Glycosphingolipids and Its Metabolites in Immunological and Inflammatory Responses in Humans.
abstract: Glycosphingolipids (GSLs) are composed of hydrophobic ceramide and hydrophilic sugar chains. GSLs cluster to form membrane microdomains (lipid rafts) on plasma membranes, along with several kinds of transducer molecules, including Src family kinases and small G proteins. However, GSL-mediated biological functions remain unclear. Lactosylceramide (LacCer, CDw17) is highly expressed on the plasma membranes of human phagocytes and mediates several immunological and inflammatory reactions, including phagocytosis, chemotaxis, and superoxide generation. LacCer forms membrane microdomains with the Src family tyrosine kinase Lyn and the Gαi subunit of heterotrimeric G proteins. The very long fatty acids C24:0 and C24:1 are the main ceramide components of LacCer in neutrophil plasma membranes and are directly connected with the fatty acids of Lyn and Gαi. These observations suggest that the very long fatty acid chains of ceramide are critical for GSL-mediated outside-in signaling. Sphingosine is another component of ceramide, with the hydrolysis of ceramide by ceramidase producing sphingosine and fatty acids. Sphingosine is phosphorylated by sphingosine kinase to sphingosine-1-phosphate, which is involved in a wide range of cellular functions, including growth, differentiation, survival, chemotaxis, angiogenesis, and embryogenesis, in various types of cells. This review describes the role of ceramide moiety of GSLs and its metabolites in immunological and inflammatory reactions in human.
authors.affiliation: Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu, Chiba 2790021, Japan ; Infection Control Nursing, Juntendo University Graduate School of Health Care and Nursing, Chiba 2790023, Japan ; Laboratory of Biochemistry, Juntendo University School of Health Care and Nursing, Chiba 2790023, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Iwabuchi
authors.affiliation: Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu, Chiba 2790021, Japan ; Laboratory of Biochemistry, Juntendo University School of Health Care and Nursing, Chiba 2790023, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu, Chiba 2790021, Japan ; Department of Dermatology, Juntendo University Urayasu Hospital, Chiba 2790021, Japan.
authors.forename: Ami
authors.initials: A
authors.lastname: Oizumi
authors.affiliation: Department of Dermatology, Juntendo University Urayasu Hospital, Chiba 2790021, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suga
authors.affiliation: Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu, Chiba 2790021, Japan.
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka Urayasu, Chiba 2790021, Japan ; Department of Dermatology, Juntendo University Urayasu Hospital, Chiba 2790021, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
mesh_terms: D002518:Ceramides / Q000502:physiology*; D006028:Glycosphingolipids / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D015603:Keratinocytes / Q000276:immunology; D008246:Lysophospholipids / Q000502:physiology; D021962:Membrane Microdomains / Q000737:chemistry; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000502:physiology
chemical_list: D002518:Ceramides; D006028:Glycosphingolipids; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine