Galectin-3 promotes adhesion of human neutrophils to laminin.
Galectin-3 is a member of a growing family of animal lectins composed of three domains, with the amino-terminal half consisting of a short segment followed by tandem repeats, and the carboxyl-terminal half representing the carbohydrate-recognition domain. Previously, we have shown that galectin-3 binds to the surface of human neutrophils and is capable of activating these cells. We have now studied the effect of exogenous galectin-3 on adhesion of human neutrophils to laminin-coated microtiter plates and found that this lectin promotes the adhesion in a dose-dependent manner. The effect was dependent on the lectin's carbohydrate-binding function, as well as its amino-terminal region. The galectin-3-induced adhesion was reduced significantly in the presence of EDTA, even though Ca2+ and Mg2+ are not required for the lectin binding, and the adhesion was significantly less at 4 degrees C, as compared with 37 degrees C. Galectin-3 also induced neutrophil adhesion to fibronectin, which is not recognized by the lectin, but much higher concentrations of the lectin were required, and the effect is completely dependent on Ca2+ and Mg2+. We conclude that galectin-3 induces neutrophil adhesion to laminin through a combination of two distinct mechanisms: 1) the lectin bridges neutrophils to laminin, in a carbohydrate-dependent and Ca2+-, Mg2+-independent manner, and 2) the lectin induces activation of neutrophils, in the presence of the divalent cations, resulting in the positive regulation of other cell adhesion molecules and enhanced adhesion to laminin. The results suggest that galectin-3 may play a role in the traversing of neutrophils through the basement membrane at inflammation sites.
Kuwabara
I
I
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Liu
F T
FT
D000595:Amino Acid Sequence / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000943:Antigens, Differentiation / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002236:Carbohydrate Conformation / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism; D037502:Galectin 3; D006801:Humans; D016023:Integrins / Q000276:immunology; D007797:Laminin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000494:pharmacology; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D013696:Temperature
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D005353:Fibronectins; D037502:Galectin 3; D016023:Integrins; D007797:Laminin; D008565:Membrane Proteins; D008274:Magnesium; D002118:Calcium