Induction of cell adhesion by galectin-8 and its target molecules in Jurkat T-cells.
We previously showed that tandem-repeat type galectin-8, which has two covalently linked carbohydrate recognition domains (CRDs), induces neutrophil-adhesion through binding to integrin alphaM. Here, we analysed the function of galectin-8 in Jurkat T-cells. Galectin-8, as well as tandem-repeat galectin-9, and several multivalent plant lectins, induced Jurkat T-cell adhesion to a culture plate, whereas single-CRD galectins-1 and -3 did not. Galectin-8 also induced the adhesion of peripheral blood leucocytes to human umbilical vein endothelial cells. These results suggest that the di- or multi-valent structure of galectin-8 is essential for the induction of cell adhesion and that this ability exhibits broad specificity for leucocytes. The galectin-8-induced cell adhesion was accompanied by stress fibre formation, which suggests that intracellular signalling is required. We have identified integrin alpha4 as one of the candidate target molecules associated with the induction of cell adhesion. Indeed, inhibition of the function of integrin alpha4 by treating cells with a blocking-antibody reduced the sensitivity to galectin-8. Also, the phosphorylation of Pyk and ERK1/2, indicators of integrin-mediated signalling, was up-regulated on treatment with galectin-8. Thus, a primary target of galectin-8 must be the sugar chains on members of the integrin family, which are abundantly expressed on the surface of leucocytic cells.
Yamamoto
Hitomi
H
Department of Endocrinology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Nishi
Nozomu
N
Shoji
Hiroki
H
Itoh
Aiko
A
Lu
Liang-Hao
LH
Hirashima
Mitsuomi
M
Nakamura
Takanori
T
D000199:Actins / Q000378:metabolism; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D037161:Galectins / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D019169:Jurkat Cells; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D037121:Plant Lectins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D000199:Actins; D037161:Galectins; D006023:Glycoproteins; D016023:Integrins; C091991:LGALS8 protein, human; C105032:LGALS9 protein, human; D008565:Membrane Proteins; D037121:Plant Lectins; D034741:RNA, Small Interfering; D003208:Concanavalin A; D048049:Extracellular Signal-Regulated MAP Kinases