“In vitro” studies on galectin-3 in human natural killer cells

Galectin-3 (Gal-3) is a β-galactoside binding protein able to modulate both innate and adaptive immune responses. First identified in macrophages, Gal-3 has been studied widely in many mammalian immune cells, but scarcely in natural killer (NK) cells. The aim of this study was to analyze Gal-3 in human NK cells, isolated from peripheral blood mononuclear cells. Both PCR and RT-PCR analysis showed that resting human NK cells express Gal-3 mRNA, which can be modulated upon cytokine stimulation (100 U/ml IL–2 + 20 ng/ml IL-15) for different period of time (1–24 h). Western blot, cytofluorimetry, and confocal microscopy analysis clearly demonstrated that the Gal-3 gene can translate into the corresponding protein. From our results, resting NK cells, isolated from different healthy donors, can express high or low basal levels of Gal-3. In NK cells, Gal-3 was always intracellularly detected at both cytoplasm and nucleus levels, while never at the membrane surface, and its localization resulted independent from the cellular activation status. In addition, the intracellular Gal-3 can co-localize with perforin in exocytic vesicles. Cell treatment with a thiodigalactoside-based Gal-3 inhibitor (1–30 μM) slightly increased the number of degranulating NK cells, while it significantly increased the percentage of cells releasing high amounts of cytotoxic granules (+ 36 ± 3% vs. inhibitor-untreated cells at 30 μM Gal-3). In conclusion, our results demonstrate that human resting NK cells express Gal-3 at both gene and protein levels and that the Gal-3 expression can be modulated upon cytokine stimulation. In the same cells, Gal-3 always localizes intracellularly and functionally correlates with the degree of NK cell degranulation

'Sweetening' Pregnancy: Galectins at the Fetomaternal Interface

Successful mammalian pregnancy relies upon acceptance of a semi-allogeneic fetus by the maternal immune system. Lessons learned from studies on protective immunity to microbial infections and tumours, prevention of autoimmunity, and allograft rejection have contributed to delineate the mechanisms leading to T-cell tolerance at the fetomaternal interface. Recent observations highlight the contribution of galectins, a family of endogenous glycan-binding proteins, to critical biological events occurring during mammalian gestation, including immune cell tolerance, inflammation, implantation, and angiogenesis. These multifunctional lectins can hierarchically control a cascade of immunoregulatory events including the expansion, recruitment, and function of regulatory T cells, the promotion of tolerogenic dendritic cells, and the execution of T-cell death programs. In addition, galectins can control cell adhesion and signaling events critical for implantation and are involved in fundamental processes linking tissue hypoxia to angiogenesis. In an attempt to integrate the regulatory roles of galectins to immunological and vascular programs operating during pregnancy. Here we outline the regulated expression and function of individual members of the galectin family within the fetoplacental unit and their biological implications for the development and preservation of successful pregnancies. © 2013 John Wiley & Sons A/S.Fil: Blidner, Ada Gabriela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; ArgentinaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin