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Eur J Immunol ; 32(4): 1069-79, 2002 04.
Article in English | MEDLINE | ID: mdl-11920574

ABSTRACT

The mechanisms controlling the formation of pseudopodia and other active cell edges in T lymphocytes are not understood. We show here that T lymphocytes express thrombospondin-1 (TSP-1). TSP-1 in T lymphocytes has a high turnover as shown by the fact that brefeldin and monensin rapidly increase while cycloheximide tend to decrease the cellular TSP-1 content. T cell TSP-1 is preferentially stored intracellularly and shows variable cell surface expression. T lymphocyte adhesion to fibronectin and collagen type IV induces TSP-1 expression on the cell surface via a brefeldin sensitive mechanism. A monoclonal antibody to TSP-1 inhibits the flattening and pseudopodia formation of the adherent T cells. Furthermore, the same antibody to TSP-1 also exerts an inhibitory effect on T cell migration in the absence of exogenous TSP-1. These results indicate that endogenous TSP-1 is part of an adhesion-dependent mechanism controlling cytoplasmic spreading and migration in T lymphocytes.


Subject(s)
T-Lymphocytes/metabolism , Thrombospondin 1/biosynthesis , Antibodies, Monoclonal/pharmacology , Brefeldin A/pharmacology , Cell Adhesion , Cell Movement/drug effects , Cells, Cultured , Cycloheximide/pharmacology , Extracellular Matrix/metabolism , Gene Expression Regulation , Humans , Monensin/pharmacology , Protein Synthesis Inhibitors/pharmacology , Protein Transport/drug effects , Pseudopodia/physiology , Pseudopodia/ultrastructure , Reverse Transcriptase Polymerase Chain Reaction , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , Thrombospondin 1/antagonists & inhibitors , Thrombospondin 1/genetics , Thrombospondin 1/immunology
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