Endogenous thrombospondin-1 is a cell-surface ligand for regulation of integrin-dependent T-lymphocyte adhesion.
Lymphocyte adhesion to cells and extracellular matrix (ECM) via integrins plays a pivotal role for the function of the immune system. We show here that endogenous thrombospondin-1 (TSP-1) is a cell-surface ligand for cis interaction of surface receptors in T lymphocytes controlled by integrins and the T-cell antigen receptor (TCR/CD3). Stimulation of CD3 triggers rapid surface expression of TSP-1 in quiescent T cells, whereas activated cells express TSP-1 constitutively. Endogenous TSP-1 is attached to lipoprotein receptor-related protein 1 (LRP1/CD91) and calreticulin (CRT) on the cell surface through its NH2-terminal domain. Adhesion via integrins to ICAM-1 or ECM components up-regulates TSP turnover dramatically from a low level in nonadherent cells, whereas CD3 stimulation inhibits TSP turnover through interference with CD91/CRT-mediated internalization. Integrin-associated protein (IAP/CD47) is essential for TSP turnover and adhesion through interaction with the C-terminal domain of TSP-1 in response to triggering signals delivered at the NH2-terminal. These results indicate that endogenous TSP-1 connects separate cell-surface receptors functionally and regulates T-cell adhesion.
Li
Shu Shun
SS
Department of Laboratory Medicine, Division of Clinical Immunology, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Liu
Zhiwen
Z
Uzunel
Mehmet
M
Sundqvist
Karl-Gösta
KG
D019921:Biotinylation; D037282:Calreticulin / Q000276:immunology; D002448:Cell Adhesion; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D008024:Ligands; D010446:Peptide Fragments / Q000737:chemistry; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D019700:Thrombospondin 1 / Q000235:genetics* / Q000276:immunology*
D037282:Calreticulin; D008024:Ligands; D010446:Peptide Fragments; D019700:Thrombospondin 1; D018799:Intercellular Adhesion Molecule-1