Evidence for extracellular superoxide dismutase as a mediator of hemorrhage-induced lung injury.
Hemorrhage results in excessive production of superoxide that is associated with severe lung injury. We examined whether the superoxide dismutase (SOD) mimetic manganese(III) mesotetrakis (di-N-ethylimidazole) porphyrin (AEOL 10150) could attenuate this lung injury and whether extracellular (EC)-SOD-deficient mice would have increased hemorrhage-induced lung injury. Compared with wild-type mice, EC-SOD-deficient mice had increased lung neutrophil accumulation, a 3.9-fold increase in myeloperoxidase activity, a 1.5-fold increase in nuclear factor (NF)-kappaB activation, and a 1.5-fold increase in lipid peroxidation 1 h after hemorrhage. Pretreatment with AEOL 10150 did not attenuate neutrophil accumulation but significantly reduced NF-kappaB activation and lipid peroxidation in both wild-type and EC-SOD-deficient mice. The increase in hemorrhage-induced neutrophil accumulation in the lungs of EC-SOD-deficient mice suggests that EC-SOD might play a role in mediating neutrophil recruitment to the lung.
Bowler
Russell P
RP
National Jewish Medical and Research Center, Denver 80206, USA. BowlerR@njc.org
Arcaroli
John
J
Abraham
Edward
E
Patel
Manisha
M
Chang
Ling-Yi
LY
Crapo
James D
JD
D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D005110:Extracellular Space / Q000201:enzymology; D006470:Hemorrhage / Q000276:immunology / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008665:Metalloporphyrins / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
C472668:AEOL 10150; D000975:Antioxidants; D008665:Metalloporphyrins; D013482:Superoxide Dismutase; D000154:Aconitate Hydratase