Hydrogen sulfide attenuates particulate matter-induced human lung endothelial barrier disruption via combined reactive oxygen species scavenging and Akt activation

Ting Wang, Lichun Wang, Syed R. Zaidi, Saad Sammani, Jessica Siegler, Liliana Moreno-Vinasco, Biji Mathew, Viswanathan Natarajan, Joe G.N. Garcia

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Exposure to particulate air pollution is associated with increased cardiopulmonary morbidity and mortality, although the pathogenic mechanisms are poorly understood. We previously demonstrated that particulate matter (PM) exposure triggers massive oxidative stress in vascular endothelial cells (ECs), resulting in the loss of EC integrity and lung vascular hyperpermeability. We investigated the protective role of hydrogen sulfide (H2S), an endogenous gaseous molecule present in the circulation, on PM-induced human lung EC barrier disruption and pulmonary inflammation. Alterations in EC monolayer permeability, as reflected by transendothelial electrical resistance (TER), the generation of reactive oxygen species (ROS), and murine pulmonary inflammatory responses, were studied after exposures to PM and NaSH, an H2S donor. Similar to N-acetyl cysteine (5 mM), NaSH (10 μM) significantly scavenged PM-induced EC ROS and inhibited the oxidative activation of p38 mitogen-activated protein kinase. Concurrent with these events, NaSH (10 μM) activated Akt, which helps maintain endothelial integrity. Both of these pathways contribute to the protective effect of H2S against PM-induced endothelial barrier dysfunction. Furthermore, NaSH (20 mg/kg) reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokinerelease in bronchoalveolar lavage fluids in a murine model of PM-induced lung inflammation. These data suggest a potentially protective role for H 2S in PM-induced inflammatory lung injury and vascular hyperpermeability.

Original languageEnglish (US)
Pages (from-to)491-496
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume47
Issue number4
DOIs
StatePublished - Oct 1 2012
Externally publishedYes

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Keywords

  • Akt
  • Endothelial permeability
  • Hydrogen sulfide
  • Particulate matter

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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