title: Independent and combined effects of prolonged inhaled nitric oxide and oxygen on lung inflammation in newborn piglets.
abstract: Clinical use of nitric oxide (NO) is usually in conjunction with high oxygen concentrations, the effects of which may include lung neutrophil accumulation, apoptosis and upregulation of antioxidant enzyme activity. To define the effects of NO on neutrophils from young piglets and its relationship to lung neutrophil dynamics during hyperoxia we exposed thirty piglets to room air (RA), RA+NO (50 ppm NO), O2 (FiO2> or =0.96) or O2+NO for 5 days. Ten additional animals breathed RA+NO or O2+NO, then recovered in RA for 3 days before sacrifice. Neutrophil CD18 and intracellular oxidant production were measured by flow cytometry. Lung apoptosis were assessed by TUNEL assay. Lung myeloperoxidase, SOD and catalase were measured biochemically. When compared to RA group, there was significant reduction in neutrophil CD18 and intracellular oxidant production in the RA+NO group, but lung MPO was unchanged. The O2 and O2+NO groups did not differ in CD18 expression or in intracellular oxidant production, but had significant increase in lung myeloperoxidase compared to the RA group. Apoptosis increased significantly only in the O2+NO group. The O2 group showed significantly increased lung SOD and catalase activity compared to the RA group, whereas the RA+NO and O2+NO groups did not. We conclude that inhaled NO at 50 ppm decreases neutrophil CD18 expression as well as intracellular oxidant production. However, this effect does not impact lung neutrophil accumulation during concurrent hyperoxia. The combination of NO and O2 exposure produces an increase in lung apoptosis. Finally, NO may prevent upregulation of SOD and catalase activity during hyperoxia, potentially increasing injury.
authors.affiliation: Pediatrics, Children's Mercy Hospital, University of Missouri at Kansas City School of Medicine, USA. iekekezie@cmh.edu
authors.forename: I I
authors.initials: II
authors.lastname: Ekekezie
authors.forename: D W
authors.initials: DW
authors.lastname: Thibeault
authors.forename: D L
authors.initials: DL
authors.lastname: Zwick
authors.forename: M H
authors.initials: MH
authors.lastname: Rezaiekhaligh
authors.forename: S M
authors.initials: SM
authors.lastname: Mabry
authors.forename: R E
authors.initials: RE
authors.lastname: Morgan
authors.forename: M
authors.initials: M
authors.lastname: Norberg
authors.forename: W E
authors.initials: WE
authors.lastname: Truog
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D018821:CD18 Antigens / Q000032:analysis; D002374:Catalase / Q000032:analysis; D004247:DNA / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D018496:Hyperoxia / Q000139:chemically induced / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D010100:Oxygen / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D009195:Peroxidase / Q000032:analysis; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000032:analysis; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D009569:Nitric Oxide; D004247:DNA; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen