Activation of the neutrophil nicotinamide adenine dinucleotide phosphate oxidase by galectin-1.
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.
Almkvist
Jenny
J
Department of Medical Microbiology and Immunology and Rheumatology, Phagocyte Research Laboratory, Göteborg University, Göteborg, Sweden. jenny.almkvist@microbio.gu.se
Dahlgren
Claes
C
Leffler
Hakon
H
Karlsson
Anna
A
D000276:Adjuvants, Immunologic / Q000097:blood / Q000378:metabolism / Q000502:physiology; D000943:Antigens, Differentiation / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003594:Cytoplasmic Granules / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004789:Enzyme Activation / Q000276:immunology; D005122:Exudates and Transudates / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D037483:Galectin 1; D037502:Galectin 3; D006388:Hemagglutinins / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019255:NADPH Oxidases / Q000097:blood / Q000378:metabolism*; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000201:enzymology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011975:Receptors, Mitogen / Q000378:metabolism; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000943:Antigens, Differentiation; D002352:Carrier Proteins; D037483:Galectin 1; D037502:Galectin 3; D006388:Hemagglutinins; D011975:Receptors, Mitogen; D019255:NADPH Oxidases