Endothelial nitric oxide synthase deficient mice are protected from lipopolysaccharide induced acute lung injury

PloS One
Christine M GrossStephen M Black

Abstract

Lipopolysaccharide (LPS) derived from the outer membrane of gram-negative bacteria induces acute lung injury (ALI) in mice. This injury is associated with lung edema, inflammation, diffuse alveolar damage, and severe respiratory insufficiency. We have previously reported that LPS-mediated nitric oxide synthase (NOS) uncoupling, through increases in asymmetric dimethylarginine (ADMA), plays an important role in the development of ALI through the generation of reactive oxygen and nitrogen species. Therefore, the focus of this study was to determine whether mice deficient in endothelial NOS (eNOS-/-) are protected against ALI. In both wild-type and eNOS-/- mice, ALI was induced by the intratracheal instillation of LPS (2 mg/kg). After 24 hours, we found that eNOS-/-mice were protected against the LPS mediated increase in inflammatory cell infiltration, inflammatory cytokine production, and lung injury. In addition, LPS exposed eNOS-/- mice had increased oxygen saturation and improved lung mechanics. The protection in eNOS-/- mice was associated with an attenuated production of NO, NOS derived superoxide, and peroxynitrite. Furthermore, we found that eNOS-/- mice had less RhoA activation that correlated with a reduction in RhoA nit...Continue Reading

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Citations

Oct 16, 2015·International Immunopharmacology·Han LiuJunping Kou
Nov 9, 2017·American Journal of Respiratory Cell and Molecular Biology·Christine M GrossStephen M Black
Jan 10, 2019·Antioxidants & Redox Signaling·Evgeny A ZemskovStephen M Black
Dec 17, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ting WangStephen M Black
Dec 6, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ping WangYinghua Chen
Jun 5, 2019·Respiratory Research·Bodil PetersenFumito Ichinose
Dec 5, 2017·Experimental Lung Research·Enqin GuanJiang Hong
Nov 26, 2020·International Journal of Molecular Sciences·Alice G VassiliouStylianos E Orfanos
Nov 28, 2020·Redox Biology·Hajera AmatullahClaudia C Dos Santos
May 25, 2021·Frontiers in Medicine·Mengdi QuChanghong Miao
Sep 17, 2021·European Respiratory Review : an Official Journal of the European Respiratory Society·Mareike GierhardtNatascha Sommer

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Methods Mentioned

BETA
GTPase
immunodepletion
Protein Assay
pulldown
dot blot
electronic paramagnetic resonance
Bronchoalveolar
lavage
Assay

Software Mentioned

GraphPad Prism
Liquid
Kodak 1D
GraphPad

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