Galectin-1 induces 12/15-lipoxygenase expression in murine macrophages and favors their conversion toward a pro-resolving phenotype

During the resolution of inflammation macrophages undergo functional changes upon exposure to pro-resolving agents in their microenvironment. Primarily, engulfment of apoptotic polymorphonuclear (PMN) cells promotes conversion of macrophages toward a pro-resolving phenotype characterized by reduced CD11b expression. These macrophages are not phagocytic, do not respond to TLR ligands, and express relatively high levels of the pro-resolving enzyme 12/15-lipoxygenase (LO). Here, we report that the immuno-regulatory lectin galectin-1 is selectively expressed by CD11bhigh, but not CD11blow macrophages. Upon exposure in vivo and ex vivo, galectin-1 directly promoted macrophage conversion from a CD11bhigh to a CD11blow phenotype and up-regulated the expression and activity of 12/15-LO. Moreover, galectin-1 treatment in vivo promoted the loss of phagocytic capacity (efferocytic satiation) in peritoneal macrophages and down-regulated secretion of TNF-α, IL-1β, and IL-10 upon LPS exposure. Our results suggest that galectin-1 could be an essential mediator in the control of macrophage function during the resolution of inflammation. Fil: Rostoker, Ran. University of Haifa. Faculty of Natural Sciences. Departament of Biology; Israel; Fil: Yaseen, Hiba. University of Haifa. Faculty of Natural Sciences. Departament of Biology; Israel; Fil: Schif Zuck, Sagie. University of Haifa. Faculty of Natural Sciences. Departament of Biology; Israel; Fil: Lichtenstein, Rachel G.. Ben-Gurion University. Department of Biotechnology Engineering; Israel; Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica; Argentina; Fil: Amiram, Ariel. University of Haifa. Faculty of Natural Sciences. Departament of Biology; Israel