Opposite effects of galectin-1 on alternative metabolic pathways of L-arginine in resident, inflammatory, and activated macrophages.
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 effects, we investigated the effects of galectin-1 in L-arginine metabolism of peritoneal rat macrophages. Pretreatment of macrophages with galectin-1 resulted in a dose- and time-dependent inhibition of lipopolysaccharide-induced nitric oxide (NO) production, 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 toward activation of L-arginase, the alternative metabolic pathway of L-arginine. Inhibition of NO production was not the result of increased macrophage apoptosis because addition of this beta-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. This 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.
Correa
Silvia G
SG
Immunology, Department of Clinical Biochemistry, School of Chemical Sciences, National University of Córdoba, Calle Haya De La Torre Esquina Medina Allende (C. 5000), Córdoba, Argentina.
Sotomayor
Claudia E
CE
Aoki
Maria P
MP
Maldonado
Cristina A
CA
Rabinovich
Gabriel A
GA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D037483:Galectin 1 / Q000096:biosynthesis / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D008854:Microscopy, Electron; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D037483:Galectin 1; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001119:Arginase