title: Extracellular superoxide dismutase in macrophages augments bacterial killing by promoting phagocytosis.
abstract: Extracellular superoxide dismutase (EC-SOD) is abundant in the lung and limits inflammation and injury in response to many pulmonary insults. To test the hypothesis that EC-SOD has an important role in bacterial infections, wild-type and EC-SOD knockout (KO) mice were infected with Escherichia coli to induce pneumonia. Although mice in the EC-SOD KO group demonstrated greater pulmonary inflammation than did wild-type mice, there was less clearance of bacteria from their lungs after infection. Macrophages and neutrophils express EC-SOD; however, its function and subcellular localization in these inflammatory cells is unclear. In the present study, immunogold electron microscopy revealed EC-SOD in membrane-bound vesicles of phagocytes. These findings suggest that inflammatory cell EC-SOD may have a role in antibacterial defense. To test this hypothesis, phagocytes from wild-type and EC-SOD KO mice were evaluated. Although macrophages lacking EC-SOD produced more reactive oxygen species than did cells expressing EC-SOD after stimulation, they demonstrated significantly impaired phagocytosis and killing of bacteria. Overall, this suggests that EC-SOD facilitates clearance of bacteria and limits inflammation in response to infection by promoting bacterial phagocytosis.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Manni
authors.forename: Lauren P
authors.initials: LP
authors.lastname: Tomai
authors.forename: Callie A
authors.initials: CA
authors.lastname: Norris
authors.forename: L Michael
authors.initials: LM
authors.lastname: Thomas
authors.forename: Eric E
authors.initials: EE
authors.lastname: Kelley
authors.forename: Russell D
authors.initials: RD
authors.lastname: Salter
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.forename: Ling-Yi L
authors.initials: LY
authors.lastname: Chang
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.forename: Jon D
authors.initials: JD
authors.lastname: Piganelli
authors.forename: Tim D
authors.initials: TD
authors.lastname: Oury
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000166:cytology*; D005110:Extracellular Space / Q000201:enzymology*; D006801:Humans; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D042541:Intracellular Space / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050296:Microbial Viability; D016877:Oxidants / Q000378:metabolism; D010587:Phagocytosis; D011014:Pneumonia / Q000382:microbiology / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D016877:Oxidants; D013482:Superoxide Dismutase