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

Cell Immunol. 2004 Nov-Dec;232(1-2):105-15. doi: 10.1016/j.cellimm.2005.02.002. Epub 2005 Apr 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / drug effects
  • Antigens, Surface / immunology
  • Glycolipids / chemical synthesis
  • Glycolipids / chemistry
  • Glycolipids / pharmacology*
  • HL-60 Cells
  • Humans
  • L-Selectin / drug effects*
  • L-Selectin / immunology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Liposomes
  • Lymphocyte Culture Test, Mixed
  • P-Selectin / drug effects
  • P-Selectin / immunology
  • Protein Binding
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Surface
  • Glycolipids
  • Liposomes
  • P-Selectin
  • sulfoquinovosylacylglycerol
  • L-Selectin