Activation of the Neutrophil Nicotinamide Adenine Dinucleotide Phosphate Oxidase by Galectin-1

Abstract

Galectins are a group of lactose-binding proteins widely distributed in nature. Twelve mammalian galectins have so far been identified, but their functions are to a large extent unknown. In this work we study galectin-1 in its interaction with human neutrophils, with regard to both cell surface binding and activation of the superoxide-producing NADPH-oxidase. We show that galectin-1 is able to activate the neutrophil NADPH-oxidase, provided that the cells have been primed by extravasation from the blood into the tissue, an activation pattern that is similar to that of galectin-3. Using in vitro priming protocols, the galectin-1 responsiveness was found to correlate to granule mobilization and galectin-1 binding to the cells, suggesting the presence of granule-localized receptors that are up-regulated to the cell surface upon priming. By galectin-1 overlay of fractionated neutrophils we identified potential galectin-1 receptor candidates localized in the membranes of the secretory vesicle and gelatinase granules. The binding of galectin-1 and galectin-3 to neutrophil proteins was compared, as were the dose dependencies for activation by the two lectins. The results suggest that, although similarities are found between the two galectins, they appear to activate the NADPH-oxidase using different receptors. In conclusion, galectin-1 appears to have proinflammatory functions, mediated through activation of the neutrophil respiratory burst.

A Novel Biological Activity for Galectin-1

“…Experiments of over-lay using PMN extracts indicated the existence of multiple potential Gal-1-binding proteins. 38 We have reproduced, at least in part, this data and shown an alteration of these bands in relation to the status of PMN activation (M La, unpublished data). Future studies will address the nature of these binding site(s), whether for instance they are analogous to those reported for Gal-3.…”

“…38 In addition, this response was achieved when cells were stimulated with a high amount of the protein (40 g/ml), well above the concentrations used here to display PMN inhibitory effects. In addition, the in vivo data discussed above clearly indicate an anti-inflammatory, rather than proinflammatory profile of Gal-1, at least in the context of acute experimental inflammation.…”

NADPH Oxidase-Derived Reactive Oxygen Species-Mediated Activation of ERK1/2 Is Required for Apoptosis of Human Neutrophils Induced by Entamoeba histolytica

“…Mammalian galectins have been found to mediate cell-cell interactions and adhesion, and to induce various intracellular signals that may regulate various cellular functions. Human recombinant galectin-1 induces activation of NADPH oxidase in human neutrophils (53) and apoptosis in T cells (54). Functional galectin-3 receptors are also identified on human neutrophils (55).…”

Galectin-1 and Its Role in Development of Innate and Adaptive Immunity

“…Названные эффекты галектина-1 говорят о его противовоспалительных свойствах, одна-ко данный белок может оказывать и провоспа-лительное действие, активируя НАДФ-оксидазу в нейтрофилах и тем самым, способствуя выходу супероксида из клеток [1].…”