title: The receptor for advanced glycation end products mediates lung endothelial activation by RBCs.
abstract: The receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor implicated in multiple disease states. Although RAGE is expressed on systemic vascular endothelium, the expression and function of RAGE on lung endothelium has not been studied. Utilizing in vitro (human) and in vivo (mouse) models, we established the presence of RAGE on lung endothelium. Because RAGE ligands can induce the expression of RAGE and stored red blood cells express the RAGE ligand N(ε)-carboxymethyl lysine, we investigated whether red blood cell (RBC) transfusion would augment RAGE expression on endothelium utilizing a syngeneic model of RBC transfusion. RBC transfusion not only increased lung endothelial RAGE expression but enhanced lung inflammation and endothelial activation, since lung high mobility group box 1 and vascular cell adhesion molecule 1 expression was elevated following transfusion. These effects were mediated by RAGE, since endothelial activation was absent in RBC-transfused RAGE knockout mice. Thus, RAGE is inducibly expressed on lung endothelium, and one functional consequence of RBC transfusion is increased RAGE expression and endothelial activation.
authors.affiliation: Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Nilam S
authors.initials: NS
authors.lastname: Mangalmurti
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Friedman
authors.forename: Liang-Chuan
authors.initials: LC
authors.lastname: Wang
authors.forename: Donna
authors.initials: D
authors.lastname: Stolz
authors.forename: Geetha
authors.initials: G
authors.lastname: Muthukumaran
authors.forename: Don L
authors.initials: DL
authors.lastname: Siegel
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.forename: Janet S
authors.initials: JS
authors.lastname: Lee
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albelda
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000502:physiology*; D057809:HEK293 Cells; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019010:Vascular Cell Adhesion Molecule-1; C048496:N(6)-carboxymethyllysine; D008239:Lysine