title: The receptor for advanced glycation end products (RAGE) contributes to the progression of emphysema in mice.
abstract: Several recent clinical studies have implied a role for the receptor for advanced glycation end products (RAGE) and its variants in chronic obstructive pulmonary disease (COPD). In this study we have defined a role for RAGE in the pathogenesis of emphysema in mice. RAGE deficient mice (RAGE-/-) exposed to chronic cigarette smoke were significantly protected from smoke induced emphysema as determined by airspace enlargement and had no significant reduction in lung tissue elastance when compared to their air exposed controls contrary to their wild type littermates. The progression of emphysema has been largely attributed to an increased inflammatory cell-mediated elastolysis. Acute cigarette smoke exposure in RAGE-/- mice revealed an impaired early recruitment of neutrophils, approximately a 6-fold decrease compared to wild type mice. Hence, impaired neutrophil recruitment with continued cigarette smoke exposure reduces elastolysis and consequent emphysema.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Pathology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Nisha
authors.initials: N
authors.lastname: Sambamurthy
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Leme
authors.affiliation: Department of Pathology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Oury
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018450:Disease Progression; D004646:Emphysema / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012906:Smoke
chemical_list: C000593873:Ager protein, mouse; D000067759:Receptor for Advanced Glycation End Products; D012906:Smoke