Submitted January 18, 2008
Accepted May 17, 2008
Endothelial CD47 interaction with SIRP
is required for human T cell transendothelial migration under shear flow conditions in vitro
Michael Stefanidakis, Gail Newton, Winston Y Lee, Charles A Parkos, and Francis W Luscinskas*
Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
Pathology, Emory University, Georgia, GA, United States
* Corresponding author; email: fluscinskas{at}rics.bwh.harvard.edu.
Leukocyte transendothelial migration (TEM) is a critical event during inflammation. CD47 has been implicated in myeloid cell migration across endothelium and epithelium. CD47 binds to signal regulatory protein (SIRP) SIRP
and SIRP
. So far, little is known about the role of endothelial CD47 in T cell TEM in vivo or under flow conditions in vitro. FACS and biochemical analysis show that CD3+ T cells express SIRP
but not SIRP
and fluorescence microscopy revealed that CD47 was enriched at endothelial junctions. These expression patterns suggested that CD47 plays a role in T cell TEM through binding interactions with SIRP
. We tested, therefore, whether CD47-SIRP
interactions affect T cell transmigration using blocking mAb against CD47 or SIRP
in an in vitro flow model. These antibodies inhibited T cell TEM by 70 ± 6% and 82 ± 1%, respectively, but had no effect on adhesion. In agreement with human mAb studies, transmigration of murine wild-type Th1 cells across TNF-
activated murine CD47-/- endothelium was reduced by 75 ± 2% even though murine T cells appear to lack SIRP
. None-the-less, these findings suggest endothelial cell CD47 interacting with T cell ligands, such as SIRP
, play an important role in T cell transendothelial migration.