title: Cellular and molecular characterization of ozone-induced pulmonary inflammation in the Cynomolgus monkey.
abstract: We investigated the cellular and molecular effects of ozone exposure in Cynomolgus monkeys. Thirty-six Cynomolgus monkeys were exposed to single or repeat ozone challenge. Pulmonary inflammation was assessed using bronchoalveolar lavage fluid (BAL) and histology. Gene expression profiling in lung and blood was performed. Ozone challenge evoked BAL cellular inflammation and increases in total protein, alkaline phosphatase and cytokines. Lung histology revealed cellular inflammation and epithelial necrosis. Gene expression profiling identified oxidative phosphorylation, immune response and cell adhesion pathways altered in response to ozone, with common and unique profiles in lung and blood. Lipocalin 2, CD177, the FK-506 and S100A8 binding proteins and ST-2 represent novel peripheral biomarkers of ozone toxicity. Repeat ozone challenge evoked reproducible inflammation but attenuated cell damage. These studies provide data on the molecular mechanisms and biomarker identification of ozone-evoked toxicity, and support the use of the Cynomolgus monkey as a model of human ozone challenge.
authors: RNA Therapeutics, Roche, Nutley, NJ 07110, USA. alexandra.hicks@roche.com
authors: Alexandra
authors: A
authors: Hicks
authors: Galina
authors: G
authors: Kourteva
authors: Holly
authors: H
authors: Hilton
authors: Hongli
authors: H
authors: Li
authors: Tai-An
authors: TA
authors: Lin
authors: Will
authors: W
authors: Liao
authors: Ying
authors: Y
authors: Li
authors: Xin
authors: X
authors: Wei
authors: Thomas
authors: T
authors: March
authors: Janet
authors: J
authors: Benson
authors: Louis M
authors: LM
authors: Renzetti
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D055745:Bronchioles / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000097:blood; D020869:Gene Expression Profiling; D008252:Macaca fascicularis; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D020545:Respiratory Mucosa / Q000473:pathology
chemical_list: D001798:Blood Proteins; D016207:Cytokines; D010083:Oxidants, Photochemical; D010126:Ozone; D000469:Alkaline Phosphatase