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Differential Roles of Galectin-1 and Galectin-3 in Regulating Leukocyte Viability and Cytokine Secretion¹

Sean R. Stowell^*, Yuning Qian, Sougata Karmakar, Natalia S. Koyama, Marcelo Dias-Baruffi, Hakon Leffler, Rodger P. McEver and Richard D. Cummings^2,*

^* Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA 30322; Section of Microbiology, Immunology, and Glycobiology, Lund University, Lund, Sweden; Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; and Departmento de Análises Clínicas, Toxicológicas e Bromatológicas da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, University of Sao Paulo, Ribeirão Preto-Sao Paulo, Brazil

Galectin-1 (Gal-1) and galectin-3 (Gal-3) exhibit profound but unique immunomodulatory activities in animals but their molecular mechanisms are incompletely understood. Early studies suggested that Gal-1 inhibits leukocyte function by inducing apoptotic cell death and removal, but recent studies show that some galectins induce exposure of the common death signal phosphatidylserine (PS) independently of apoptosis. In this study, we report that Gal-3, but not Gal-1, induces both PS exposure and apoptosis in primary activated human T cells, whereas both Gal-1 and Gal-3 induce PS exposure in neutrophils in the absence of cell death. Gal-1 and Gal-3 bind differently to the surfaces of T cells and only Gal-3 mobilizes intracellular Ca²⁺ in these cells, although Gal-1 and Gal-3 bind their respective T cell ligands with similar affinities. Although Gal-1 does not alter T cell viability, it induces IL-10 production and attenuates IFN- production in activated T cells, suggesting a mechanism for Gal-1-mediated immunosuppression in vivo. These studies demonstrate that Gal-1 and Gal-3 induce differential responses in T cells and neutrophils, and identify the first factor, Gal-3, capable of inducing PS exposure with or without accompanying apoptosis in different leukocytes, thus providing a possible mechanism for galectin-mediated immunomodulation in vivo.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant P01 HL085607 (to R.P.M. and R.D.C.) and Swedish Research Council Grant 12165 (to H.L.).

² Address correspondence and reprint requests to Dr. Richard D. Cummings, Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, No. 4001, Atlanta, GA 30322. E-mail address: rdcummi{at}emory.edu

³ Abbreviations used in this paper: Gal, galectin; TDG, thiodigalactoside; PS, phosphatidylserine; iGal, iodoacetamide-treated Gal; PFH, paraformaldehyde; PI, propidium iodide.

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