title: Dietary advanced glycation end-products, its pulmonary receptor, and high mobility group box 1 in aspiration lung injury.
abstract: BACKGROUND
  Gastric aspiration is a significant cause of acute lung injury and acute respiratory distress syndrome. Environmental risk factors, such as a diet high in proinflammatory advanced glycation end-products (AGEs), may render some patients more susceptible to lung injury after aspiration. We hypothesized that high dietary AGEs increase its pulmonary receptor, RAGE, producing an amplified pulmonary inflammatory response in the presence of high mobility group box 1 (HMGB1), a RAGE ligand and an endogenous signal of epithelial cell injury after aspiration.
  
  
  METHODS
  CD-1 mice were fed either a low AGE or high AGE diet for 4 wk. After aspiration injury with acidified small gastric particles, bronchoalveolar lavage and whole-lung tissue samples were collected at 5 min, 1 h, 5 h, and 24 h after injury. RAGE, soluble RAGE (sRAGE), HMGB1, cytokine and chemokine concentrations, albumin levels, neutrophil influx, and lung myeloperoxidase activity were measured.
  
  
  RESULTS
  We observed that high AGE-fed mice exhibited greater pulmonary RAGE levels before aspiration and increased bronchoalveolar lavage sRAGE levels after aspiration compared with low AGE-fed mice. Lavage HMGB1 levels rose immediately after aspiration, peaking at 1 h, and strongly correlated with sRAGE levels in both dietary groups. High AGE-fed mice demonstrated higher cytokine and chemokine levels with increased pulmonary myeloperoxidase activity over 24 h versus low AGE-fed mice.
  
  
  CONCLUSIONS
  This study indicates that high dietary AGEs can increase pulmonary RAGE, augmenting the inflammatory response to aspiration in the presence of endogenous damage signals such as HMGB1.
authors.affiliation: Department of Surgery, University at Buffalo-State University of New York, Buffalo, New York; Department of Anesthesiology, University at Buffalo-State University of New York, Buffalo, New York. Electronic address: pjsmit@buffalo.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smit
authors.affiliation: Department of Surgery, University at Buffalo-State University of New York, Buffalo, New York.
authors.forename: Weidun A
authors.initials: WA
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, University at Buffalo-State University of New York, Buffalo, New York.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Davidson
authors.affiliation: Department of Anesthesiology, University at Buffalo-State University of New York, Buffalo, New York.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Mullan
authors.affiliation: Department of Anesthesiology, University at Buffalo-State University of New York, Buffalo, New York.
authors.forename: Jadwiga D
authors.initials: JD
authors.lastname: Helinski
authors.affiliation: Department of Anesthesiology, University at Buffalo-State University of New York, Buffalo, New York.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology / Q000378:metabolism*; D000418:Albumins / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002199:Capillary Permeability; D016207:Cytokines / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology; D024243:HMGB1 Protein / Q000378:metabolism*; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011015:Pneumonia, Aspiration / Q000276:immunology / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism
chemical_list: D000418:Albumins; D016207:Cytokines; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009195:Peroxidase
keywords: Acute lung injury; Advanced glycation end-products; Gastric aspiration; High mobility group box 1; Receptor for advanced glycation end-products