Submitted April 17, 2006
Accepted June 23, 2006
Endogenous thrombospondin-1 is a cell surface ligand for regulation of integrin dependent T lymphocyte adhesion
Shu Shun Li, Zhiwen Liu, Mehmet Uzunel, and Karl-Gosta Sundqvist*
Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden
* Corresponding author; email: karl.sundqvist{at}karolinska.se.
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 while activated cells express TSP-1 constitutively. Endogenous TSP-1 is attached to lipoprotein receptor related protein (LRP/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 non-adherent cells while 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.
