Inhibitory control of endothelial galectin-1 on in vitro and in vivo lymphocyte trafficking.
Galectin-1 (Gal-1) is a beta-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 hypersensitivity. 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
Lucy V
LV
The William Harvey Research Institute, Barts, and The London, Charterhouse Square, London EC1M 6BQ, UK.
Sampaio
André L F
AL
Cooper
Dianne
D
Perretti
Mauro
M
D000818:Animals; D002464:Cell Migration Inhibition / Q000187:drug effects*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D037483:Galectin 1 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D006968:Hypersensitivity, Delayed; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
D037483:Galectin 1