Integrin‐associated protein (CD47/IAP) contributes to T cell arrest on inflammatory vascular endothelium under flow

ABSTRACT Integrin‐associated protein (CD47/IAP) is a pentaspan molecule that regulates integrin functions. We prepared a CD47‐deficient Jurkat T cell line to assess its role in the arrest of T cells on inflammatory endothelium. Under flow conditions, constitutive arrest of CD47‐deficient cells is strongly decreased as compared to the original cell line, whereas reexpression of CD47 reestablishes their ability to stop. Moreover, cells transfected with a chimera made with the extracellular portion of CD47 and the transmembrane domain of CD7 or several truncated forms of CD47 show that the first transmembrane domain and a short cytoplasmic loop are sufficient for this process. CD47 effect is indirect and depends mainly on the α 4β1/VCAM‐1 pathway, as shown by blocking antibodies. We detected on endothelium the two CD47 counter receptors known to date: thrombospondin and SIRP1 α . Blocking experiments show that both are involved. Overall, CD47 participates in the constitutive arrest of T lymphocytes on inflamed vascular endothelium by up‐regulating a 4β1 integrins.—Ticchioni, M., Raimondi, V., Lamy, L., Wijdenes, J., Lindberg, F. P., Brown, E. J., Bernard, A. Integrin‐associated protein (CD47/IAP) contributes to T cell arrest on inflammatory vascular endothelium under flow. FASEB J. 15, 341‐350 (2001)