1. ¹Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA
2. ²Department of Dermatology, UC Davis School of Medicine, Davis, CA 95616, USA
3. ³Howard Hughes Medical Institute, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

Correspondence: LG Baum, Department of Pathology and Laboratory Medicine, UCLA School of Medicine, 10833 LeConte Ave., Los Angeles, CA 90095-1732, USA. Tel: 310-206-5985; fax: 310-206-0657; E-mail: lbaum@mednet.ucla.edu

Received 5 November 2003; Accepted 6 May 2004; Published online 6 August 2004.

Abstract

Galectin-1, a mammalian lectin expressed in many tissues, induces death of diverse cell types, including lymphocytes and tumor cells. The galectin-1 T cell death pathway is novel and distinct from other death pathways, including those initiated by Fas and corticosteroids. We have found that galectin-1 binding to human T cell lines triggered rapid translocation of endonuclease G from mitochondria to nuclei. However, endonuclease G nuclear translocation occurred without cytochrome c release from mitochondria, without nuclear translocation of apoptosis-inducing factor, and prior to loss of mitochondrial membrane potential. Galectin-1 treatment did not result in caspase activation, nor was death blocked by caspase inhibitors. However, galectin-1 cell death was inhibited by intracellular expression of galectin-3, and galectin-3 expression inhibited the eventual loss of mitochondrial membrane potential. Galectin-1-induced cell death proceeds via a caspase-independent pathway that involves a unique pattern of mitochondrial events, and different galectin family members can coordinately regulate susceptibility to cell death.