D-galactosyl-beta1-1'-sphingosine and D-glucosyl-beta1-1'-sphingosine induce human natural killer cell apoptosis.
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.
Maghazachi
Azzam A
AA
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
Knudsen
Eirunn
E
Jin
Yixin
Y
Jenstad
Monica
M
Chaudhry
Farrukh A
FA
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*
C513334:GPR65 protein, human; D006028:Glycosphingolipids; D043562:Receptors, G-Protein-Coupled; D013110:Sphingosine