A novel biological activity for galectin-1: Inhibition of leukocyte-endothelial cell interactions in experimental inflammation
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Galectin-1 (Gal-1), the prototype of a family of β -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 μg equivalent to 20 pmol) inhibited interleukin-1β-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 post-adherent 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.
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galectin 1, antiinflammatory activity, cell compartmentalization, cell interaction, chronic inflammation, endothelium cell, experimental infection, extracellular matrix, extravasation, gene sequence, human, human cell, inflammatory cell, leukocyte, neutrophil, peritoneal cavity, priority journal, protein family, Animals, Binding Sites, Cell Communication, Cell Movement, Chemotaxis, Leukocyte, Dose-Response Relationship, Drug, Endothelium, Vascular, Flow Cytometry, Galectin 1, Humans, Injections, Interleukin-1, Interleukin-8, Leukocyte Rolling, Male, Mice, Neutrophils, Peritonitis, Recombinant Proteins
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Inglês
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American Journal of Pathology, v. 163, n. 4, p. 1505-1515, 2003.
