title: D-galactosyl-beta1-1'-sphingosine and D-glucosyl-beta1-1'-sphingosine induce human natural killer cell apoptosis.
abstract: Natural killer (NK) cells perform multiple biological functions including tumor cell lysis and eradicating virally infected cells. Here, we report for the first time that D-galactosyl-beta1-1' sphingosine and D-glucosyl-beta1- 1' sphingosine damage human NK cells. We show that these cells express T-cell-associated gene-8, the receptor for glycosphingolipids. D-galactosyl-beta1-1' sphingosine and D-glucosyl-beta1-1' sphingosine induce the in vitro chemotaxis of human NK cells. Both D-galactosyl-beta1-1' sphingosine and D-glucosyl-beta1-1' sphingosine inhibit the cytotoxicity and IFN-gamma secretion by these cells. Further analysis shows that the glycosphingolipids D-galactosyl-beta1-1' sphingosine and D-glucosyl-beta1-1' sphingosine but not any other lipid examined, which include D-lactosyl-beta1-1' sphingosine, sphingosine 1-phosphate, sphingosine, lysophosphatidic acid, and phosphatidic acid, induce the apoptosis, globoid-like formation, and multinucleation in human NK cells. These results may have important implications on diseases where glycosphingolipids accumulate.
authors.affiliation: Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, P.O.B. 1105 Blindern, N-0317 Oslo, Norway. azzam.maghazachi@basalmed.uio.no
authors.forename: Azzam A
authors.initials: AA
authors.lastname: Maghazachi
authors.forename: Eirunn
authors.initials: E
authors.lastname: Knudsen
authors.forename: Yixin
authors.initials: Y
authors.lastname: Jin
authors.forename: Monica
authors.initials: M
authors.lastname: Jenstad
authors.forename: Farrukh A
authors.initials: FA
authors.lastname: Chaudhry
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006028:Glycosphingolipids / Q000494:pharmacology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013110:Sphingosine / Q000494:pharmacology*
chemical_list: C513334:GPR65 protein, human; D006028:Glycosphingolipids; D043562:Receptors, G-Protein-Coupled; D013110:Sphingosine