engleski

The role of galectin-3 in classicaly and alternatively activated macrophages

The differentiation of monocytes (Mo) into macrophages (Mf) during migration from blood into the nearby tissues is followed by tremendous changes of their biology. Mf can be differentiated into two distinct phenotypes known as classical (M1), which promote a TH1 response, killing of intracellular pathogens and inflammatory mediator release and alternatively activated (M2) macrophages, generally oriented to tissue remodeling and repair, immunoregulation, and tumor promotion. During these processes, the expression of thousands of proteins is modulated, including a pro-inflammatory lectin, galectin-3 (Gal-3). This β-galactose-binding galectin is a key regulator of both innate and acquired immunity, and participates in all phases of the inflammatory response. Gal-3 promotes monocyte respiratory burst, macrophage chemotaxis and phagocytosis. The aim of this study was to explore the expression of Gal-3 during human macrophage differentiation and activation. Mo were isolated from healthy blood donors and differentiated into two distinct subtypes using granulocyte-macrophage (GM-) or macrophage colony- stimulating factor (M-CSF) which wre additionally activated classically by IFN-γ and LPS, or alternatively, using IL-4/IL-10 to generate M2a/c cells, respectively. Differentiation of monocytes into M1 and M2 and their activation is followed by significant differences in Gal-3 expression, secretion and proteolitic cleavage. Interestingly, considerable diversities of 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.

Tolieja; Lithuania

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