Galectin-3 functions as an adhesion molecule to support eosinophil rolling and adhesion under conditions of flow.
Allergic inflammation involves the mobilization and trafficking of eosinophils to sites of inflammation. Galectin-3 (Gal-3) has been shown to play a critical role in eosinophil recruitment and airway allergic inflammation in vivo. The role played by Gal-3 in human eosinophil trafficking was investigated. Eosinophils from allergic donors expressed elevated levels of Gal-3 and demonstrated significantly increased rolling and firm adhesion on immobilized VCAM-1 and, more surprisingly, on Gal-3 under conditions of flow. Inhibition studies with specific mAbs as well as lactose demonstrated that: 1) eosinophil-expressed Gal-3 mediates rolling and adhesion on VCAM-1; 2) alpha(4) integrin mediates eosinophil rolling on immobilized Gal-3; and 3) eosinophil-expressed Gal-3 interacts with immobilized Gal-3 through the carbohydrate recognition domain of Gal-3 during eosinophil trafficking. These findings were further confirmed using inflamed endothelial cells. Interestingly, Gal-3 was found to bind to alpha(4) integrin by ELISA, and the two molecules exhibited colocalized expression on the cell surface of eosinophils from allergic donors. These findings suggest that Gal-3 functions as a cell surface adhesion molecule to support eosinophil rolling and adhesion under conditions of flow.
Rao
Savita P
SP
Division of Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego, CA 92121, USA.
Wang
Zhuangzhi
Z
Zuberi
Riaz I
RI
Sikora
Lyudmila
L
Bahaie
Nooshin S
NS
Zuraw
Bruce L
BL
Liu
Fu-Tong
FT
Sriramarao
P
P
D001783:Blood Flow Velocity; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D037502:Galectin 3 / Q000502:physiology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D039441:Integrin alpha4 / Q000276:immunology; D036904:Leukocyte Rolling / Q000276:immunology*; D011485:Protein Binding; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D015815:Cell Adhesion Molecules; D037502:Galectin 3; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4