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Endogenous thrombospondin-1 is a cell-surface ligand for regulation of integrin-dependent T-lymphocyte adhesion.
Umeå University, Faculty of Medicine, Clinical Microbiology, Clinical Immunology.
2006 (English)In: Blood, ISSN 0006-4971, Vol. 108, no 9, 3112-3120 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2006. Vol. 108, no 9, 3112-3120 p.
URN: urn:nbn:se:umu:diva-27751DOI: 10.1182/blood-2006-04-016832PubMedID: 16835379OAI: diva2:277470
Available from: 2009-11-18 Created: 2009-11-18 Last updated: 2009-11-18

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