title: Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction.
abstract: Acute Cl2 exposure following industrial accidents or military/terrorist activity causes pulmonary injury and severe acute respiratory distress. Prior studies suggest that antioxidant depletion is important in producing dysfunction, however a pathophysiologic mechanism has not been elucidated. We propose that acute Cl2 inhalation leads to oxidative modification of lung lining fluid, producing surfactant inactivation, inflammation and mechanical respiratory dysfunction at the organ level. C57BL/6J mice underwent whole-body exposure to an effective 60ppm-hour Cl2 dose, and were euthanized 3, 24 and 48h later. Whereas pulmonary architecture and endothelial barrier function were preserved, transient neutrophilia, peaking at 24h, was noted. Increased expression of ARG1, CCL2, RETLNA, IL-1b, and PTGS2 genes was observed in bronchoalveolar lavage (BAL) cells with peak change in all genes at 24h. Cl2 exposure had no effect on NOS2 mRNA or iNOS protein expression, nor on BAL NO3(-) or NO2(-). Expression of the alternative macrophage activation markers, Relm-α and mannose receptor was increased in alveolar macrophages and pulmonary epithelium. Capillary surfactometry demonstrated impaired surfactant function, and altered BAL phospholipid and surfactant protein content following exposure. Organ level respiratory function was assessed by forced oscillation technique at 5 end expiratory pressures. Cl2 exposure had no significant effect on either airway or tissue resistance. Pulmonary elastance was elevated with time following exposure and demonstrated PEEP refractory derecruitment at 48h, despite waning inflammation. These data support a role for surfactant inactivation as a physiologic mechanism underlying respiratory dysfunction following Cl2 inhalation.
authors.affiliation: Department of Pharmacology & Toxicology, Ernest Mario School of Pharmacy, Rutgers University, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Massa
authors.affiliation: Department of Pharmacology & Toxicology, Ernest Mario School of Pharmacy, Rutgers University, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Scott
authors.affiliation: Department of Pharmacology & Toxicology, Ernest Mario School of Pharmacy, Rutgers University, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Abramova
authors.affiliation: Department of Pharmacology & Toxicology, Ernest Mario School of Pharmacy, Rutgers University, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Gardner
authors.affiliation: Department of Pharmacology & Toxicology, Ernest Mario School of Pharmacy, Rutgers University, USA.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
authors.affiliation: Department of Pharmacology & Toxicology, Ernest Mario School of Pharmacy, Rutgers University, USA. Electronic address: Gow@rci.rutgers.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gow
mesh_terms: D000403:Airway Resistance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002713:Chlorine / Q000633:toxicity*; D004548:Elasticity; D004781:Environmental Exposure; D005740:Gases; D005786:Gene Expression Regulation; D007113:Immunity, Innate / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008170:Lung Compliance; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability; D011014:Pneumonia / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011175:Positive-Pressure Respiration; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012129:Respiratory Function Tests; D013997:Time Factors
chemical_list: D015415:Biomarkers; D005740:Gases; D018836:Inflammation Mediators; D037661:Pulmonary Surfactant-Associated Proteins; D012333:RNA, Messenger; D002713:Chlorine
keywords: Alternative activation; Bronchoalveolar lavage; Nitric oxide; Pulmonary mechanics; Respiratory impedance