Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow

William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry, Charterhouse Square, London, UK.
Journal of Leukocyte Biology (Impact Factor: 4.29). 07/2008; 83(6):1459-66. DOI: 10.1189/jlb.1207831
Source: PubMed


Galectin-1 (Gal-1) is a beta-galactoside-binding protein endowed with anti-inflammatory properties. The purpose of this study was to investigate the effects of endogenous and exogenous Gal-1 on neutrophil recruitment onto TNF-treated endothelium. The effect of human recombinant (hr)Gal-1 on markers of neutrophil activation (CD11b expression, P-selectin glycoprotein ligand 1, and L-selectin shedding) was also assessed. Gal-1 inhibited the platelet-activating factor-induced increase in CD11b expression in a concentration-dependent manner, as assessed by flow cytometry. To determine the effects of Gal-1 on neutrophil recruitment, an in vitro flow chamber was used: Preincubation of neutrophils with hrGal-1 significantly decreased the extent of capture, rolling, and adhesion on activated endothelial monolayers. This inhibition was shared with the endogenous protein, as knockdown of endothelial Gal-1 using small interfering RNA resulted in a significant increase in the number of cells captured and rolling. To verify the effects of Gal-1 in an in vivo system, intravital microscopy of Gal-1 null mice and their wild-type counterparts was performed. Leukocyte adhesion and emigration were increased significantly in the cremasteric circulation of Gal-1 null mice inflamed with IL-1beta. These findings indicate that Gal-1 functions to limit neutrophil recruitment onto a TNF-treated endothelium, a property that may underline its inhibitory effects in acute inflammation.


Available from: Mauro Perretti
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    • "Continued leukocyte recruitment might also be caused by malfunctioning of restraining or homeostatic mechanisms. More specifically, a number of endogenous inhibitors of leukocyte recruitment have been described [53], including pentraxin 3 (PTX- 3) [54], developmental endothelial locus-1 (del-1) [55], galectin-1 [56] [57], and growth differentiation factor 15 (GDF-15) [58]. It is therefore reasonable to assume that an inhibition or decreased availability of these factors can contribute to continued leukocyte recruitment. "
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    • "Further investigation into the mechanism revealed that galectin-1 treatment enhanced the susceptibility of T cells to antigen-induced apoptosis, increased T cell adhesion to extracellular matrix, and also inhibited IL-2 secretion from collagen-specific T cell hybridomas [54,56,57]. In addition, galectin-1 functions to limit neutrophil recruitment to TNF-treated endothelium; and leukocyte adhesion and emigration were significantly increased in galectin-1-deficient mice inflamed with IL-1β [69]. In a more recent study, galectin-1-deficient mice exhibited increased susceptibility to CIA, with earlier onset of arthritis and more severe manifestations than the wild type mice [70]. "
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