A Novel Function for Galectin-1 at the Crossroad of Innate and Adaptive Immunity: Galectin-1 Regulates Monocyte/Macrophage Physiology through a Nonapoptotic ERK-Dependent Pathway

Abstract

Several environmental factors can differentially regulate monocyte and macrophage response patterns, resulting in the display of distinct functional phenotypes. Galectin-1, an endogenous lectin found at peripheral lymphoid organs and inflammatory sites, has shown immunoregulatory activity in vivo in experimental models of autoimmunity and cancer. Whereas compelling evidence has been accumulated regarding the effects of galectin-1 on T cell fate, limited information is available on how galectin-1 may impact other immune cell types. In the present study, we report a novel role for galectin-1 in the regulation of monocyte and macrophage physiology. Treatment with galectin-1 in vitro differentially regulates constitutive and inducible FcγRI expression on human monocytes and FcγRI-dependent phagocytosis. In addition, galectin-1 inhibits IFN-γ-induced MHC class II (MHC-II) expression and MHC-II-dependent Ag presentation in a dose-dependent manner. These regulatory effects were also evident in mouse macrophages recruited in response to inflammatory stimuli following treatment with recombinant galectin-1 and further confirmed in galectin-1-deficient mice. Investigation of the mechanisms involved in these functions showed that galectin-1 does not affect survival of human monocytes, but rather influences FcγRI- and MHC-II-dependent functions through active mechanisms involving modulation of an ERK1/2-dependent pathway. Our results provide evidence of a novel unrecognized role for galectin-1 in the control of monocyte/macrophage physiology with potential implications at the crossroad of innate and adaptive immunity.

Glycan-dependent binding of galectin-1 to neuropilin-1 promotes axonal regeneration after spinal cord injury

“…Given the different biological activities of monomeric versus dimeric Gal-1 species, we used a Gal-1 mutant (M-Gal-1), which exists in a monomeric form even at high concentrations. 35 M-Gal-1 treatment in Lgals1 À / À mice induced a similar locomotor behavior than treatment with vehicle control in WT mice showing a BBB score of B4 ± 0.49 (Supplementary Figure S6a). Both groups evidenced a limited capacity to keep on the top of the bridge-shaped metal grid by balancing on their front limbs, with little use of their tails and no involvement of their hindlimbs (Supplementary Figures S6b-e).…”

Functions of cell surface galectin-glycoprotein lattices

“…Moreover, by interacting with specific saccharide ligands, galectin-1 differentially regulates Fcγ receptor I-dependent phagocytosis and inhibits major histocompatibility complex (MHC)-II-dependent antigen presentation by monocytes/macrophages [31].…”

Molecular and functional characterization of a tandem-repeat galectin from the freshwater snail Biomphalaria glabrata, intermediate host of the human blood fluke Schistosoma mansoni

“…Despite their narrow ligand binding affinity for β-galactosides, galectins have been implicated in a diversity of cellular functions including cell adhesion/proliferation, development/morphogenesis, tumor cell metastasis and immune regulation/innate immunity (Hughes, 2002;Vasta et al, 2004a;Zick et al, 2004;Camby et al, 2006). The role of galectins as effectors or modulators of the immune response has been most extensively studied in vertebrates where they have been implicated in apoptotic regulation of B/T-cell populations, cytokine signaling, monocyte/macrophage-mediate inflammation and microbe phagocytosis (Sano et al, 2003;Young and Meeusen, 2004;AcostaRodriguez et al, 2004;Liu, 2005;Rubinovitch and Gruppi, 2005;Rubinstein et al, 2006;Barrionuevo et al, 2007).…”