engleski

Differentiation and activation of macrophages: a galectin-3 perspective

Galectin-3 (Gal-3), a β-galactoside lectin, is mainly considered to advance inflammation: it triggers/promotes monocyte respiratory burst, acts as a monocyte (Mc)/macrophage (Mf) chemoattractant and promotes the survival of inflammatory cells. Depending on environmental cues, Mc/Mf exhibit diverse biological characteristics, but two main subtypes, classically (M1) and alternatively (M2) differentiated and activated Mf have been recognized. This study explores the expression of Gal-3 in the physiology of these cells. Monocytes from healthy blood donors were differentiated to M1 or M2 cells using macrophage colony-stimulating factor (M-CSF) or granulocyte- macrophage colony- stimulating factor (GM-CSF), respectively. Macrophages were then activated classically by IFN-γ and LPS, or alternatively, using IL-4/IL-10 to generate M2a/c cells. Gene and protein expression levels of intra- and extracellular Gal- 3 were investigated by qRT-PCR, Western-blot, flow cytometry, imunoprecipitation and ELISA, while surface Gal-3 receptor expression was analyzed by flow cytometry. Differentiation of Mc and classical/alternative Mf activation was followed by marked changes of Gal-3 expression and proteolitic cleavage. Furthermore, its expression and secretion were tightly regulated and significantly differed among distinctly differentiated and activated Mf. Interestingly, considerable differences in Gal-3 expression profiles were observed among the same Mf subtypes, obtained from different donors. Upon activation by IFN-γ and LPS, M1 (but not M2) macrophages diverged into distinct populations with respect to membrane Gal-3 expression. Human Mc had a high amount of free Gal-3 receptors, while on activated Mf the receptors were fully saturated. Specific expression and secretion patterns of Gal- 3 in differentiated and activated Mf contribute to better understanding of its role in these cells, and provide an important insight into macrophage biological characteristics.

galectin-3; macrophages

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