title: Inhibition of CD62L+ T-cell response in vitro via a novel sulfo-glycolipid, beta-SQAG9 liposome that binds to CD62L molecule on the cell surface.
abstract: We previously reported that synthetic sulfo-glycolipid, 3-O-(6-deoxy-6-sulfono-beta-D-glucopyranosyl)-1,2-di-O-acylglycerol (beta-SQDG(18:0)) which was deduced from sulfonoquinovosyl-diacylglycerols of sea urchin possessed immunosuppressive effects, such as human mixed lymphocyte reaction (MLR) and skin allograft in rat, and that these effects were caused by contact inhibition between T-cells and antigen presenting cells (APCs). Here, we investigated the mechanism of these immunosuppressive effects on human MLR by beta-SQAG9 which had been newly synthesized from beta-SQDG(18:0) to improve structural stability in water solution. CD62L+ T-cells in peripheral blood predominantly respond to APCs, and beta-SQAG9 inhibited the response of CD62L+ T-cell subset in human allogeneic MLR. Surprisingly, it was demonstrated that beta-SQAG9 bound to L- and P-selectin (CD62L and P) molecule in vitro. Meanwhile, beta-SQAG9 efficiently formed liposome structure and bound to L-selectin on the cell surface of CD62L+ T-cell subset but might not be incorporated into the cells. Because the immunosuppressive effects of beta-SQAG9 disappeared when beta-SQAG9 liposome was changed to soluble form by detergent, the liposome structure of beta-SQAG9 was presumed to be essential for these effects. These findings suggested beta-SQAG9 to be a novel drug with a unique immunosuppressive action.
authors.affiliation: Division of Plastic Surgery, Sapporo Medical University School of Medicine, South 1 West 17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hiroeki
authors.initials: H
authors.lastname: Sahara
authors.forename: Mika
authors.initials: M
authors.lastname: Takenouchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Akihito
authors.initials: A
authors.lastname: Imai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujita
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Shinsei
authors.initials: S
authors.lastname: Gasa
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohta
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.forename: Kengo
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Kowichi
authors.initials: K
authors.lastname: Jimbow
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000954:Antigens, Surface / Q000187:drug effects / Q000276:immunology; D006017:Glycolipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D019041:L-Selectin / Q000187:drug effects* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008081:Liposomes; D007959:Lymphocyte Culture Test, Mixed; D019007:P-Selectin / Q000187:drug effects / Q000276:immunology; D011485:Protein Binding; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; D006017:Glycolipids; D008081:Liposomes; D019007:P-Selectin; C496611:sulfoquinovosylacylglycerol; D019041:L-Selectin