Glycobiology Advance Access published online on November 1, 2002
Glycobiology, doi:10.1093/glycob/cwg010
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© 2002 Oxford University Press
ORIGINAL ARTICLES
1 Immunology, Departament of Clinical Biochemistry. School of Chemical Sciences. National University of Córdoba Recent evidence has implicated galectins and their carbohydrate ligands as master regulators of the inflammatory response. Galectin-1, a member of this family has shown specific anti-inflammatory and immunoregulatory effects. To gain insight into the potential mechanisms involved in these anti-inflammatory effects, in the present study we investigated the effects of galectin-1 in L-arginine metabolism of peritoneal rat macrophages. Pre-treatment of macrophages with galectin-1 resulted in a dose- and time-dependent inhibition of lipopolysaccharide-induced nitric oxide (NO) production, which was accompanied by a decrease in inducible nitric oxide synthase (iNOS) expression (the classic pathway of L-arginine). On the other hand, galectin-1 favored the balance towards activation of L-arginase, the alternative metabolic pathway of L-arginine. Inhibition of NO production was not the result of increased macrophage apoptosis, since addition of this
Revised on September 8, 2002
Accepted on September 10, 2002
Opposite effects of galectin-1 on alternative metabolic pathways of L-arginine in resident, inflammatory and activated macrophages
2 Centre of Electron Microscopy. School of Medicine. National University of Córdoba
3 Division of Immunogenetics. Hospital de Clínicas "José de San Martín". School of Medicine. University of Buenos Aires.
-galactoside-binding protein to macrophages under the same experimental conditions did not affect the apoptotic threshold of these cells. To understand how endogenous galectin-1 is regulated in macrophages under inflammatory stress, we finally explored the ultrastructural distribution, expression and secretion of galectin-1 in resident, inflammatory and activated macrophages. The present study provides an alternative cellular mechanism, based on the modulation of L-arginine metabolism, to understand the molecular basis of the anti-inflammatory properties displayed by this carbohydrate-binding protein.
Key words: galectins/ inflammation/ L-arginine metabolism/ macrophages/ nitric oxide
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