Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow.
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.
Cooper
Dianne
D
William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry, Charterhouse Square, London, UK. d.cooper@qmul.ac.uk
Norling
Lucy V
LV
Perretti
Mauro
M
D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement; D005260:Female; D037483:Galectin 1 / Q000032:analysis / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000494:pharmacology
D039481:CD11b Antigen; D037483:Galectin 1; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D010972:Platelet Activating Factor; D034741:RNA, Small Interfering