Salicylates inhibit T cell adhesion on endothelium under nonstatic conditions: induction of L-selectin shedding by a tyrosine kinase-dependent mechanism. 2001

R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
Section of Internal Medicine, Center for the Study of Rheumatic Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Italy. gerlir@unipg.it

Salicylates inhibit T cell adhesion to and transmigration through endothelium by preventing integrin activation induced by contact with endothelial cells. In the present study the effects of aspirin and sodium salicylate on the first steps of T cell adhesion have been analyzed in a nonstatic in vitro system. Salicylates partially reduced adhesion to activated endothelium and, in parallel, L-selectin expression on resting T cells by inducing shedding of the molecule without affecting its mRNA transcript. The role of L-selectin down-regulation in reducing T cell adhesion in this system was supported by the fact that aspirin inhibited T cell adhesion also on plastic-immobilized L-selectin ligand or when alpha(4) integrin-mediated adhesion to endothelium was blocked by specific mAbs. In addition, preincubation of T cells with inhibitors of L-selectin shedding prevented both functional and phenotypic inhibitory effects of salicylates. The decrease in T cell adhesion and L-selectin expression seems to be dependent on intracellular calcium increase and tyrosine kinase activation, because these effects could be reversed by preincubating salicylate-treated T cells with EGTA, genistein, or tyrphostin. Finally, the infusion of aspirin into healthy volunteers induced down-regulation of L-selectin on circulating T cells. These results suggest that salicylates interfere not only with integrin activation, but also with the L-selectin-mediated first steps of T cell binding to endothelium.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D007424 Intracellular Fluid The fluid inside CELLS. Fluid, Intracellular,Fluids, Intracellular,Intracellular Fluids
D007983 Lewis Blood Group Antigens Carbohydrate antigens structurally related to the ABH BLOOD-GROUP SYSTEM. They may occur as a modification of saccharide chains on glycolipids or glycoproteins on cell surfaces or in plasma, or as free oligosaccharides in secretions. Lewis antigens are not synthesized in blood cells. Instead Lewis glycolipids present in plasma are absorbed onto the surface of ERYTHROCYTES; LYMPHOCYTES; and PLATELETS. The phenotypes Le(a) and Le(b) are the result of the actions of two genes the Le gene (fucosyltransferase FUT3) and the Se gene (fucosyltransferase FUT2) on the precursor carbohydrate, glycolipid or glycoprotein. Other FUCOSYLTRANSFERASES can also synthesize the Lewis antigens. Blood Group Lewis Related Antigens,Lewis Antigen Related Tumor-Associated Antigens,Lewis Antigens,Lewis Blood Group Related Antigens,Lewis Blood Group Related Tumor-Associated Antigens,Lewis Blood-Group System,Lewis Related Antigens,Lewis System,Sialyl Lewis Antigens,Le Antigens,Le(a) Blood Group System,Antigens, Lewis,Antigens, Lewis Related,Antigens, Sialyl Lewis,Blood-Group System, Lewis,Lewis Antigen Related Tumor Associated Antigens,Lewis Blood Group Related Tumor Associated Antigens,Lewis Blood Group System
D008666 Metalloendopeptidases ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism. Metallo-Endoproteinases,Metalloendopeptidase
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D002474 Cell-Free System A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166) Cellfree System,Cell Free System,Cell-Free Systems,Cellfree Systems,System, Cell-Free,System, Cellfree,Systems, Cell-Free,Systems, Cellfree

Related Publications

R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
June 1992, The Journal of experimental medicine,
R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
September 1994, Journal of immunology (Baltimore, Md. : 1950),
R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
June 1997, Journal of immunology (Baltimore, Md. : 1950),
R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
March 1997, Blood,
R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
January 1996, European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes,
R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
October 2000, European journal of immunology,
R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
February 1997, Journal of immunology (Baltimore, Md. : 1950),
R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
April 1996, Blood,
R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
June 1995, Cellular immunology,
R Gerli, and P Gresele, and O Bistoni, and C Paolucci, and L Lanfrancone, and S Fiorucci, and C Muscat, and V Costantini
January 1998, Journal of immunology (Baltimore, Md. : 1950),
Copied contents to your clipboard!