Opposite effects of galectin-1 on alternative metabolic pathways of L-arginine in resident, inflammatory, and activated macrophages

Glycobiology. 2003 Feb;13(2):119-28. doi: 10.1093/glycob/cwg010. Epub 2002 Nov 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Arginase / metabolism
  • Arginine / metabolism*
  • Blotting, Western
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Female
  • Flow Cytometry / methods
  • Galectin 1 / biosynthesis
  • Galectin 1 / pharmacology*
  • Immunohistochemistry
  • Inflammation / metabolism
  • Macrophage Activation
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Macrophages / metabolism*
  • Microglia / cytology
  • Microglia / drug effects
  • Microglia / ultrastructure
  • Microscopy, Electron
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Rats
  • Rats, Wistar
  • Time Factors


  • Galectin 1
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Arginase