Premium
Inhibitory control of endothelial galectin‐1 on in vitro and in vivo lymphocyte trafficking
Author(s) -
Norling Lucy V.,
Sampaio André L. F.,
Cooper Dianne,
Perretti Mauro
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/fj.07-9268com
Subject(s) - microbiology and biotechnology , galectin 1 , lymphocyte homing receptor , chemistry , homing (biology) , cd43 , endothelial stem cell , endothelium , receptor , proinflammatory cytokine , inflammation , cell adhesion , immunology , in vitro , biology , cell , antigen , biochemistry , endocrinology , ecology , cd20
Galectin‐1 (Gal‐1) is a β‐galactoside‐binding protein, the expression of which is increased in endothelial cells on exposure to proinflammatory stimuli. Through binding of several receptors (CD7, CD45, and CD43) Gal‐1 is known to induce apoptosis of activated T lymphocytes, an effect thought to mediate the beneficial effects it exerts in various inflammatory models. The data presented here highlights another function for Gal‐1, that of a negative regulator of T‐cell recruitment to the endothelium under both physiological and pathophysiological conditions. We have shown, using siRNA to knockdown Gal‐1 in endothelial cells, that endogenous Gal‐1 limits T‐cell capture, rolling, and adhesion to activated endothelial cells under flow. Furthermore, the reverse effect is observed when exogenous human recombinant Gal‐1 is added to activated endothelial monolayers whereby a dramatic reduction in lymphocyte recruitment is seen. These findings are corroborated by studies in Gal‐1 null mice in which homing of wild‐type (WT) T lymphocytes is significantly increased to mesenteric lymph nodes and to the inflamed paw in a model of delayed‐type hyper‐sensitivity. In conclusion, mimicking endothelial Gal‐1 actions would be a novel strategy for controlling aberrant T‐cell trafficking, hence for the development of innovative anti‐inflammatory therapeutics.—Norling, L. V., Sampaio, A. L. F., Cooper, D., Perretti, M. Inhibitory control of endothelial galectin‐1 on in vitro and in vivo lymphocyte trafficking. FASEB J . 22, 682–690 (2008)