Acid sphingomyelinase inhibition protects mice from lung edema and lethal Staphylococcus aureus sepsis.

ABSTRACT:

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Pulmonary edema associated with increased vascular permeability is a severe complication of Staphylococcus aureus-induced sepsis and an important cause of human pathology and death. We investigated the role of the mammalian acid sphingomyelinase (Asm)/ceramide system in the development of lung edema caused by S. aureus. Our findings demonstrate that genetic deficiency or pharmacologic inhibition of Asm reduced lung edema in mice infected with S. aureus. The Asm/ceramide system triggered the formation of superoxide, resulting in degradation of tight junction proteins followed by lung edema. Treatment of infected mice with amitriptyline, a potent inhibitor of Asm, protected mice from lung edema caused by S. aureus, but did not reduce systemic bacterial numbers. In turn, tr

SUBMITTER: Peng H 

PROVIDER: S-EPMC4432103 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature