A human lectin, galectin-3 (epsilon bp/Mac-2), stimulates superoxide production by neutrophils.
A family of soluble animal lectins, galectins, with beta-galactoside-binding activity, is gaining increased attention. One member of this family, galectin-3, has been previously designated by this group as epsilon bp, for its IgE-binding activity. On the basis of the saccharide specificity and other biochemical characteristics of epsilon bp, it is possible that this lectin could have an important extracellular modulatory role, functioning through recognition of critical cell surface glycoproteins on many cell types. We present evidence here that recombinant human epsilon bp activates human neutrophils in a dose-dependent manner as demonstrated by superoxide production. The observed activity is dependent on the lectin property of epsilon bp intrinsic to its carboxyl-terminal domain, as it could be inhibited effectively by lactose, a known saccharide ligand of epsilon bp. However, the amino-terminal domain is also necessary for the observed activity, as epsilon bp-C (the carboxyl-terminal domain fragment) is devoid of neutrophil-activating activity, even though it retains the carbohydrate-binding property. Affinity purification of lysates from cell surface-radio-iodinated neutrophils revealed two major protein bands of M(r) 115,000 and M(r) 180,000 that are recognized by epsilon bp and preliminary data suggested that one of these proteins is NCA-160, a human carcinoembryonic Ag-related glycoprotein. This study thus lends further support to our view of an extracellular function for epsilon bp and suggests that this protein has an important role in inflammation and host defense through modulating the function of neutrophils.
Yamaoka
A
A
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037.
Kuwabara
I
I
Frigeri
L G
LG
Liu
F T
FT
D000943:Antigens, Differentiation / Q000502:physiology*; D002241:Carbohydrates / Q000502:physiology; D002846:Chromatography, Affinity; D004591:Electrophoresis, Polyacrylamide Gel; D037502:Galectin 3; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D037102:Lectins / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism*
D000943:Antigens, Differentiation; D002241:Carbohydrates; D037502:Galectin 3; D037102:Lectins; D013481:Superoxides