Molecular mechanism of leukocyte activation by galectin via integrin family

点击翻译按钮获取中文摘要

Galectins are members of an animal lectin family, which specifically recognizes P-galactoside structure of glycoconjugates. In this study, we attempted to analyze the molecular mechanism of the functions and their signaling of tandem repeat galectins, such as galectins-8 and-9 in immune cells. First, we compared the effects of galectins-8 and-9on the apoptosis and cell adhesion in various immune cell lines. Galectin-9 induced apoptosis of Tell lines (Jurkat and Molt-4), but galectin-8 did not Both of galectins mediated the cell adhesion to plastic culture plates in B-cell lines(Namalwa, and RPM-8866) and a monocytic cell (THP-1) in addition of T-cell lines. In the present study, we examined the properties of galectin-9-mediated cell death of Jurkat T-cells. Galectin-9NC (wild-type), consisting of two CRDs (N-terminal and C-terminal carbohydrate recognition domains), and derivatives of it, galectins-9-NN and-9-CC, induced Jurkat T-cell apoptosis. However, a single CRD (galectin-9NT or-CT) had no effect, suggesting the stable dimeric structure of two CRDs is required for the activity. The apoptosis was inhibited by pretreatment with an N-glycan synthesis inhibitor, indicating that the expression of N-glycans in the cells is essential for galectin-9-induced apoptosis. We previously showed that the apoptosis of MOLT-4 cell is mediated by galectin-9 via a Ca^<2+>-calpain-caspase-1-dependent pathway. In Jurkat cells, the cell death by galectin-9, was insufficiently suppressed by caspase inhibitors, Ca^<2+>-chelator or calpain inhibitor. Furthermore, we observed the loss of mitochondrial membrane potential and significant AIF release in galectin-9-treated cells. These findings suggest that caspase-dependent and-independent death pathways exist in Jurkat cells, and the main pathway might vary with the T-cell type.