Blockade of RAGE suppresses alloimmune reactions in vitro and delays allograft rejection in murine heart transplantation.

Abstract	The receptor for advanced glycation endproducts (RAGE), a multiligand member of the immunoglobulin superfamily, interacts with proinflammatory AGEs, the products of nonenzymatic glycation and oxidation of proteins; high-mobility group box 1 (HMGB1), also known as amphoterin and S100/calgranulins to amplify inflammation and tissue injury. Previous studies showed that blockade of RAGE suppressed recruitment of proinflammatory mechanisms in murine models. We tested the hypothesis that RAGE contributes to alloimmune responses and report that in vivo, acute rejection of fully allogeneic cardiac allografts in a murine model of heterotopic cardiac transplantation is significantly delayed by pharmacological antagonism of RAGE. In parallel, allogeneic T-cell proliferation in the mixed lymphocyte reaction is, at least in part, RAGE-dependent. These data provide the first insights into key roles for RAGE in allorecognition responses and suggest that antagonism of this receptor may exert beneficial effects in allogeneic organ transplantation.
Authors	B Moser, M J Szabolcs, H J Ankersmit, Y Lu, W Qu, A Weinberg, K C Herold, A M Schmidt
Journal	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 7 Issue 2 Pg. 293-302 (Feb 2007) ISSN: 1600-6135 [Print] United States
PMID	17241110 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Glycation End Products, Advanced Ligands Receptor for Advanced Glycation End Products Receptors, Immunologic
Topics	Animals Apoptosis Cell Proliferation Cells, Cultured Glycation End Products, Advanced Graft Rejection (immunology, prevention & control) Heart Transplantation (adverse effects, immunology, pathology) Humans Ligands Lymphocyte Culture Test, Mixed Male Mice Mice, Inbred C57BL Receptor for Advanced Glycation End Products Receptors, Immunologic (antagonists & inhibitors, physiology) T-Lymphocytes (immunology, pathology) Transplantation Tolerance (immunology)

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