Analysis of the role of galectin family and its signaling in the host-response to infection and inflammation.

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Galectins are members of an animal lectin family, which specifically recognizes B-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 examined the effect of galectin-8 on the activation of human peripheral neutrophils. The results revealed that N-terminal CRD(carbohydrate recognition domain) of galectin-8 bound pormatrix metalloproteinase-9 (proMMP-9) and C-terminal CRD bound integrin αM and proMMP-9. The processing of ProMMP-9 on the surface of neutrophils was accelerated by binding of galectin-8, and the superoxide production in neutrophils was stimulated by the interaction between integrin αM and galectin-8. Second, we compared the effects of galectins-8 and -9 on the apoptosis and cell adhesion in various immune cell lines. Galectin-9 induced apoptosis of T-cell 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 RPMI-8866) and a monocytic cell (THP-1) in addition of T-cell lines. A target candidate for galectin-8 in Jurkat cells was identified to be integrin α4, which associates with cell adhesion. Third, linker peptide regions joining of the two CRDs of tandem repeat type galectins-8 and -9, were deleted by recombinant protein engineering. The linker-deleted mutants (null galectins) are resistant to proteases. The satble null galectins maintained high biological activities in immune cell functions such as cell adhesion and chemoattraction. Thus, tandem repeat galectins have multile roles in natural immunocytes and cell lines. And one of their main targets may be integrin faimily. Furthermore, the stable galectins must be useful tools for analysis of galectin functions and the development of medicine for immune diseases.