Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion.
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-gamma 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.
Stowell
Sean R
SR
Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Qian
Yuning
Y
Karmakar
Sougata
S
Koyama
Natalia S
NS
Dias-Baruffi
Marcelo
M
Leffler
Hakon
H
McEver
Rodger P
RP
Cummings
Richard D
RD
D016923:Cell Death / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D037483:Galectin 1 / Q000502:physiology*; D037502:Galectin 3 / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D010718:Phosphatidylserines / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; D037483:Galectin 1; D037502:Galectin 3; C445499:LGALS1 protein, human; D010718:Phosphatidylserines; D016753:Interleukin-10; D007371:Interferon-gamma