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Endothelial CD47 interaction with SIRP‐γ is essential for T cell transendothelial migration in vitro
Author(s) -
Stefanidakis Michael,
Parkos Charles A,
Luscinskas Francis W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.666.1
Subject(s) - cd47 , microbiology and biotechnology , endothelial stem cell , endothelium , integrin , biology , in vitro , cell , chemistry , biochemistry , phagocytosis , endocrinology
6006‐AAI Leukocyte transendothelial migration (TEM) is a critical event in inflammation and requires sequential action of several families of adhesion molecules. CD47 or Integrin‐Associated Protein (IAP) is a 50kD transmembrane protein that belongs to the IgSF and is highly expressed on platelets, leukocytes, endothelial and epithelial cells, and neurons. CD47 is known to bind two members of the signal regulatory protein family, SIRPα and SIRPγ. So far, little is know about the role of endothelial CD47 in T cell TEM under physiological flow conditions in vitro or in vivo . FACS and Western blot analysis show that CD3+ T cells express SIRPγ but not SIRPα. Confocal microscopy showed that CD47 was enriched at endothelial junctions, suggesting a role for CD47 in T cell TEM. To determine the role of endothelial CD47 in T cell TEM, function blocking mAb to CD47 or SIRPγ were used in an in vitro flow model of TEM. mAb to CD47 or SIRPγ inhibited T cell TEM by 65 % and 75 % (n=4), respectively, but had no effect on adhesion. Both blocking mAb also decreased T cell apical migration velocity. Strikingly, the TEM of murine T helper 1 cells through TNF‐α activated murine CD47 deficient endothelium was inhibited by 80 % (n=2). In summary, these data indicate that interactions between endothelial CD47 and SIRPγ play an important role in T cell TEM under flow conditions. Support by grants from the American Heart Association and NIH HL36028.