T lymphocyte expression of thrombospondin-1 and adhesion to extracellular matrix components.
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.
Li
Shu Shun
SS
Department of Clinical Immunology, Umeå University, Umeå, Sweden.
Ivanoff
Anna
A
Bergström
Sten-Erik
SE
Sandström
Anders
A
Christensson
Birger
B
van Nerven
Joost
J
Holgersson
Jan
J
Hauzenberger
Dan
D
Arencibia
Ignacio
I
Sundqvist
Karl-Gösta
KG
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008985:Monensin / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D011554:Pseudopodia / Q000502:physiology / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D011500:Protein Synthesis Inhibitors; D019700:Thrombospondin 1; D020126:Brefeldin A; D008985:Monensin; D003513:Cycloheximide