engleski

Galectin-3 in human monocyte/macrophage activation.

Galectin-3 (Gal-3) is a β-galactoside binding protein, a key lectin which regulates (patho)physiological processes of innate and acquired immunity. Generally considered a powerful pro-inflammatory signal, Gal-3 triggers/promotes monocyte respiratory burst, acts as a monocyte/macrophage chemoattractant and promotes survival of inflammatory cells. The aim of this study was to explore the roles of exogenous Gal-3 on the (patho)physiology of monocytic lineage cells and ascertain the level of Gal-3 expression in said cells. Using cytokine capture beads and flow cytometry we studied the effect of recombinant human Gal-3 on inflammatory cytokine secretion of classically (M1) or alternatively activated (M2a/c) macrophages. PBMC-derived monocytes from healthy volunteers were exposed to macrophage colony- stimulating factor (MCSF), IFN- γ and LPS to generate M1 or granulocyte-macrophage colony- stimulating factor (GMCSF) and IL-4/IL-10 to generate M2a/c cells. M1 polarization was confirmed by elevated TNF-α, IL-1ß and IL-6 in culture medium and lack of CD206 mannose receptor in respect to M2 macrophages. Dead cells were excluded by 7AAD. Used Gal-3 concentration did not induce significant apoptosis. Our data indicate IL-8 could be considered a novel M1 vs. M2 polarization marker. Exogenous Gal-3 was shown to upregulate IL-6 and IL-8 in M2a cells and TNF-α, IL-6 and IL-8 in M2c cells, skewing M2 towards the pro-inflammatory M1 phenotype. The expression level of Gal-3 was determined by Western blotting in monocytes, M1 and M2a/c cells. Preliminary data show difference in number and molecular weight of discrete Gal-3 isotypes in monocytes and M1, M2a and M2c macrophage subtypes. Significant variability of Gal-3 expression was also detected in samples obtained from different healthy blood donors. Collected data provide new insights into Gal-3 biological roles and contribute setting up a platform for development of new anti-inflammatory therapeutic approaches.

galectin-3; macrophage; monocyte

DOI: 10.1111/j.1742-4658.2011.08137.x