Journal
MOLECULAR IMMUNOLOGY
Volume 41, Issue 1, Pages 9-18Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2004.02.004
Keywords
apoptosis; T lymphocytes; molecular biology; spleen and lymph nodes; autoimmunity
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Galectin-1 is a homodimeric protein with potent anti-inflammatory properties due to its ability to induce apoptosis in thymocytes and T cells. The galectin-1 subunits are not covalently linked but the monomers are in a dynamic equilibrium with the dimeric form. Since the affinity of the monomers for each other is rather low (in the range of 10(-5) M), the in vivo efficacy of galectin-1 is limited because the equilibrium is shifted towards the inactive monomeric form at lower concentrations. In order to overcome this problem, we designed a covalently linked form of the dieter based on the galectin-1 crystal structure. Here we show that this irreversibly dimeric form of galectin-1 is a potent inducer of apoptosis in murine thymocytes as well as murine mature T cells at concentrations 10-fold lower than wild-type galectin-1. This structurally optimized form of galectin-1 may therefore be a potentially powerful tool to treat chronic inflammatory diseases. (C) 2004 Elsevier Ltd. All rights reserved.
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