Galectin-3 but not galectin-1 induces mast cell death by oxidative stress and mitochondrial permeability transition.
Galectin-1 and galectin-3 are the most ubiquitously expressed members of the galectin family and more importantly, these two molecules are shown to have opposite effects on pro-inflammatory responses and/or apoptosis depending on the cell type. Herein, we demonstrate for the first time that galectin-3 induces mast cell apoptosis. Mast cells expressed substantial levels of galectin-3 and galectin-1 and to a lesser extent the receptor for advanced glycation end products (RAGE) on their surfaces. Treatment of cells with galectin-3 at concentrations of > or =100 nM for 18-44 h resulted in cell death by apoptosis. Galectin-3-induced apoptosis was completely prevented by lactose, neutralizing antibody to RAGE, and the caspase-3 inhibitor z-DEVD-fmk. Galectin-3-induced apoptosis was also completely abolished by dithiothreitol and superoxide dismutase, but not inhibited by catalase. Moreover, galectin-3 but not galectin-1 induced the release of superoxide, which was blocked by lactose, anti-RAGE, and dithiothreitol. Finally, galectin-3-induced apoptosis was blocked by bongkrekic acid, an antagonist of the mitochondrial permeability transition pore (PTP), while atractyloside, an agonist of the PTP, greatly facilitated galectin-1-induced apoptosis. These data suggest that galectin-3 induces oxidative stress, PTP opening, and the caspase-dependent death pathway by binding to putative surface receptors including RAGE via the carbohydrate recognition domain.
Suzuki
Yoshihiro
Y
Division of Molecular Cell Immunology and Allergology, Nihon University Graduate School of Medical Sciences, Tokyo, Japan. ysuzuki@med.nihon-u.ac.jp
Inoue
Toshio
T
Yoshimaru
Tetsuro
T
Ra
Chisei
C
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D037483:Galectin 1 / Q000378:metabolism* / Q000494:pharmacology; D037502:Galectin 3 / Q000378:metabolism* / Q000494:pharmacology; D007785:Lactose / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry
D037483:Galectin 1; D037502:Galectin 3; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013438:Sulfhydryl Compounds; D007785:Lactose