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 s egment followed by tandem repeats, and the carboxyl-terminal half repr esenting the carbohydrate-recognition domain. Previously, we have show n that galectin-3 binds to the surface of human neutrophils and is cap able of activating these cells. We have now studied the effect of exog enous galectin-3 on adhesion of human neutrophils to laminin-coated mi crotiter plates acid found that this lectin promotes the adhesion in a dose-dependent manner. The effect was dependent on the lectin's carbo hydrate-binding function, as well as its amino-terminal region. The ga lectin-3-induced adhesion was reduced significantly in the presence of EDTA, even though Ca2+ and Mg2+ are not required for the lectin bindi ng, and the adhesion was significantly less at 4 degrees C, as compare d with 37 degrees C. Galectin-3 also induced neutrophil adhesion to fi bronectin, which is not recognized by the lectin, but much higher conc entrations of the lectin were required, and the effect is completely d ependent on Ca2+ and Mg2+ We conclude that galectin-3 induces neutroph il adhesion to laminin through a combination of two distinct mechanism s: 1) the lectin bridges neutrophils to laminin, in a carbohydrate-dep endent and Ca2+-, Mg2+-independent manner, and 2) the lectin induces a ctivation of neutrophils, in the presence of the divalent cations, res ulting 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 mem brane at inflammation sites.