Galectin-3 and galectin-1 bind distinct cell surface glycoprotein receptors to induce T cell death.
Galectins are a family of mammalian beta-galactoside-binding proteins that positively and negatively regulate T cell death. Extracellular galectin-1 directly induces death of T cells and thymocytes, while intracellular galectin-3 blocks T cell death. In contrast to the antiapoptotic function of intracellular galectin-3, we demonstrate that extracellular galectin-3 directly induces death of human thymocytes and T cells. However, events in galectin-3- and galectin-1-induced cell death differ in a number of ways. Thymocyte subsets demonstrate different susceptibility to the two galectins: whereas galectin-1 kills double-negative and double-positive human thymocytes with equal efficiency, galectin-3 preferentially kills double-negative thymocytes. Galectin-3 binds to a complement of T cell surface glycoprotein receptors distinct from that recognized by galectin-1. Of these glycoprotein receptors, CD45 and CD71, but not CD29 and CD43, appear to be involved in galectin-3-induced T cell death. In addition, CD7 that is required for galectin-1-induced death is not required for death triggered by galectin-3. Following galectin-3 binding, CD45 remains uniformly distributed on the cell surface, in contrast to the CD45 clustering induced by galectin-1. Thus, extracellular galectin-3 and galectin-1 induce death of T cells through distinct cell surface events. However, as galectin-3 and galectin-1 cell death are neither additive nor synergistic, the two death pathways may converge inside the cell.
Stillman
Brianna N
BN
Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, University of California Los Angeles (UCLA) School of Medicine, Los Angeles, CA 90095, USA.
Hsu
Daniel K
DK
Pang
Mabel
M
Brewer
C Fred
CF
Johnson
Pauline
P
Liu
Fu-Tong
FT
Baum
Linda G
LG
D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D037483:Galectin 1 / Q000378:metabolism* / Q000494:pharmacology; D037502:Galectin 3 / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051917:Leukosialin / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000302:isolation & purification / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; C068126:CD71 antigen; D037483:Galectin 1; D037502:Galectin 3; D019012:Integrin beta1; C445499:LGALS1 protein, human; D051917:Leukosialin; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; C465014:SPN protein, human; D017493:Leukocyte Common Antigens