A novel biological activity for galectin-1: inhibition of leukocyte-endothelial cell interactions in experimental inflammation.
Galectin-1 (Gal-1), the prototype of a family of beta-galactoside-binding proteins, has been shown to attenuate experimental acute and chronic inflammation. In view of the fact that endothelial cells (ECs), but not human polymorphonuclear leukocytes (PMNs), expressed Gal-1 we tested here the hypothesis that the protein could modulate leukocyte-EC interaction in inflammatory settings. In vitro, human recombinant (hr) Gal-1 inhibited PMN chemotaxis and trans-endothelial migration. These actions were specific as they were absent if Gal-1 was boiled or blocked by neutralizing antiserum. In vivo, hrGal-1 (optimum effect at 0.3 micro g equivalent to 20 pmol) inhibited interleukin-1beta-induced PMN recruitment into the mouse peritoneal cavity. Intravital microscopy analysis showed that leukocyte flux, but not their rolling velocity, was decreased by an anti-inflammatory dose of hrGal-1. Binding of biotinylated Gal-1 to resting and postadherent human PMNs occurred at concentrations inhibitory in the chemotaxis and transmigration assays. In addition, the pattern of Gal-1 binding was differentially modulated by PMN or EC activation. In conclusion, these data suggest the existence of a previously unrecognized function of Gal-1, that is inhibition of leukocyte rolling and extravasation in experimental inflammation. It is possible that endogenous Gal-1 may be part of a novel anti-inflammatory loop in which the endothelium is the source of the protein and the migrating PMNs the target for its anti-inflammatory action.
D000818:Animals; D001665:Binding Sites; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005434:Flow Cytometry; D037483:Galectin 1 / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007267:Injections; D007375:Interleukin-1 / Q000008:administration & dosage; D016209:Interleukin-8 / Q000494:pharmacology; D036904:Leukocyte Rolling / Q000187:drug effects; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000473:pathology; D010538:Peritonitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology
D037483:Galectin 1; D007375:Interleukin-1; D016209:Interleukin-8; D011994:Recombinant Proteins