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.
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.
Yamamoto
Yoshiteru
Y
Division of Plastic Surgery, Sapporo Medical University School of Medicine, South 1 West 17, Chuo-ku, Sapporo 060-8556, Japan.
Sahara
Hiroeki
H
Takenouchi
Mika
M
Matsumoto
Yoshitaka
Y
Imai
Akihito
A
Fujita
Tatsuya
T
Tamura
Yasuaki
Y
Takahashi
Nobuaki
N
Gasa
Shinsei
S
Matsumoto
Kenjiro
K
Ohta
Keisuke
K
Sugawara
Fumio
F
Sakaguchi
Kengo
K
Jimbow
Kowichi
K
Sato
Noriyuki
N
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*
D000954:Antigens, Surface; D006017:Glycolipids; D008081:Liposomes; D019007:P-Selectin; C496611:sulfoquinovosylacylglycerol; D019041:L-Selectin