engleski

Galectin-3 in Macrophage Differentiatin and Activation

Galectin-3 (Gal-3) is a β-galactoside lectin which modulates many processes of innate and acquired immunity. Generally considered a potent pro- inflammatory signal, Gal-3 triggers/promotes monocyte respiratory burst, acts as a monocyte/macrophage chemoattractant and promotes the survival of inflammatory cells. In response to a broad range of environmental cues, monocytes and macrophages exhibit different biological and biochemical characteristics, but two main subtypes, classically (M1) or alternatively (M2) differentiated and activated macrophages have been recognized. The aim of this study was to explore the expression of Gal-3 in the physiology of said human macrophages. Human monocytes from healthy blood donors were differentiated into M1 or M2 cells using macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), respectively. Obtained macrophages were activated classically by IFN-γ and LPS, or alternatively, using IL-4/IL-10 to generate M2a/c cells. Macrophage polarization was confirmed by flow cytometric profiling of secreted cytokines and distinct surface markers expression. 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. Obtained results imply that differentiation of monocytes into classically and alternatively activated macrophages is followed by marked changes of Gal-3 expression and proteolitic cleavage. Furthermore, its expression and secretion were tightly regulated and significantly differed among classically and alternatively activated macrophages. Interestingly, considerable differences in galectin-3 expression profiles were observed among the same macrophage subtypes obtained from different blood donors. In response to IFN-γ/LPS, classically activated macrophages polarize into two distinct populations with respect to the membrane galectin-3 expression. Human monocytes have a high amount of free galectin-3 receptors, while on both types of activated macrophages the receptors were fully saturated. Specific expression and secretion patterns of Gal- 3 in M1 vs. M2a/M2c macrophages contribute to better understanding of its role and regulation in these cells and provide an important new insight into the biological characteristics of these cells.

galectin-3; macrophage differentiation & activation

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