Cholesterylphosphoserine as inhibitor of cell adhesion and actin polymerization in human T cells.
To further investigate the immunosuppressive activity of cholesterylphosphoserine (CPHS), we examined a variety of human T cell responses including proliferation, adhesion and cytoskeletal organization. The CPHS-induced inhibition of T cell response is greater in the integrin-dependent mixed lymphocyte reaction than in the integrin-independent proliferation elicited by anti-TCR-CD3 or anti-CD28 antibodies in the presence of tetradecanoylphorbol acetate. Consistently, CPHS inhibits the homotypic T cell adhesion involving the integrin alphaLbeta2 (LFA-1) and the cell adhesion to fibronectin and rVCAM-1 involving the integrins of the beta1 family. Since CPHS does not change integrin expression but inhibits post-receptor events such as cell spreading and pseudopodal projections, it seems likely that the site of CPHS influence is distal to the adhesion receptors. In agreement, the steroid prevents the reorganization of actin cytoskeleton occurring when T cells are allowed to spread on immobilized anti-CD3 in the absence of integrin activation. We suggest that CPHS acts on the metabolic pathway in which signals from integrin and growth factor receptors converge to induce the reorganization of the actin cytoskeleton. Selectivity in the action of CPHS is indicated by its ineffectiveness in the integrin-mediated adhesion of the monocytic cell line U-937 to fibronectin.
Cusinato
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F
Department of Pharmacology, University of Padua, Largo Meneghetti 2, 35131, Padua, Italy.
Carrara
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M
Bova
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S
Bruni
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A
D000199:Actins / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D010768:Phosphoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011108:Polymers; D011493:Protein Kinase C / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000199:Actins; D005353:Fibronectins; D011108:Polymers; D019010:Vascular Cell Adhesion Molecule-1; C097061:cholesterylphosphorylserine; D010768:Phosphoserine; D002784:Cholesterol; D011493:Protein Kinase C