title: Leukocyte-derived extracellular superoxide dismutase does not contribute to airspace EC-SOD after interstitial pulmonary injury.
abstract: The antioxidant enzyme extracellular superoxide dismutase (EC-SOD) is abundant in the lung and is known to limit inflammation and fibrosis following numerous pulmonary insults. Previous studies have reported a loss of full-length EC-SOD from the pulmonary parenchyma with accumulation of proteolyzed EC-SOD in the airspace after an interstitial lung injury. However, following airspace only inflammation, EC-SOD accumulates in the airspace without a loss from the interstitium, suggesting this antioxidant may be released from an extrapulmonary source. Because leukocytes are known to express EC-SOD and are prevalent in the bronchoalveolar lavage fluid (BALF) after injury, it was hypothesized that these cells may transport and release EC-SOD into airspaces. To test this hypothesis, C57BL/6 wild-type and EC-SOD knockout mice were irradiated and transplanted with bone marrow from either wild-type mice or EC-SOD knockout mice. Bone marrow chimeric mice were then intratracheally treated with asbestos and killed 3 and 7 days later. At both 3 and 7 days following asbestos injury, mice without pulmonary EC-SOD expression but with EC-SOD in infiltrating and resident leukocytes did not have detectable levels of EC-SOD in the airspaces. In addition, leukocyte-derived EC-SOD did not significantly lessen inflammation or early stage fibrosis that resulted from asbestos injury in the lungs. Although it is not influential in the asbestos-induced interstitial lung injury model, EC-SOD is still known to be present in leukocytes and may play an influential role in attenuating pneumonias and other inflammatory diseases.
authors: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Michelle L
authors: ML
authors: Manni
authors: Michael W
authors: MW
authors: Epperly
authors: Wei
authors: W
authors: Han
authors: Timothy S
authors: TS
authors: Blackwell
authors: Steven R
authors: SR
authors: Duncan
authors: Jon D
authors: JD
authors: Piganelli
authors: Tim D
authors: TD
authors: Oury
mesh_terms: D000818:Animals; D001194:Asbestos / Q000008:administration & dosage* / Q000009:adverse effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000201:enzymology; D016166:Free Radical Scavengers / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology; D007962:Leukocytes / Q000201:enzymology*; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D055370:Lung Injury / Q000201:enzymology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D001194:Asbestos; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase