title: Acid aspiration-induced lung inflammation and injury are exacerbated in NADPH oxidase-deficient mice.
abstract: Increased reactive oxidant intermediates (ROIs) from primed leukocytes have been implicated in the pathogenesis of acid aspiration lung injury. To evaluate the specific role of the phagocyte NADPH oxidase-derived ROIs in acid lung injury, the p47phox-/- knockout mouse model of chronic granulomatous disease was used. p47phox-/- mice developed a significantly greater alveolar neutrophilic leukocytosis compared with wild-type mice at all time points after acid injury, with the difference between genotypes being most marked at 48 h. In contrast, the p47phox-/- mice had a decreased number of macrophages in bronchoalveolar lavage (BAL) compared with wild-type at 48 h after acid or saline aspiration. Albumin concentration in BAL reflecting capillary leak was also greater in p47phox-/- compared with wild-type mice. BAL concentrations of proinflammatory cytokines and chemokines were greater in p47phox-/- compared with wild-type mice. These findings suggest that NADPH oxidase, directly or indirectly, plays a role in attenuating the acute neutrophilic response after acid lung injury. We speculate that this downmodulating effect may be mediated by promoting the transition from production of cytokines and chemokines involved in neutrophilic infiltration to a less injurious, chronic inflammatory response.
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, University at Buffalo-State University of New York, Buffalo, NY 14214-3013, USA.
authors.forename: Brahm H
authors.initials: BH
authors.lastname: Segal
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Davidson
authors.forename: Alan D
authors.initials: AD
authors.lastname: Hutson
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Russo
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Holm
authors.forename: Barbara
authors.initials: B
authors.lastname: Mullan
authors.forename: Michael
authors.initials: M
authors.lastname: Habitzruther
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
mesh_terms: D000143:Acids / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004322:Drainage / Q000379:methods*; D005260:Female; D018496:Hyperoxia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D020556:Neutrophil Infiltration; D010586:Phagocytes / Q000166:cytology / Q000378:metabolism; D011014:Pneumonia / Q000201:enzymology* / Q000209:etiology / Q000473:pathology
chemical_list: D000143:Acids; D018925:Chemokines; D016207:Cytokines; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1