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2624195 
Journal Article 
Abstract 
The protective role of hydrogen sulfide in attenuating particulate matter-induced endothelial barrier disruption 
Wang, T; Zaidi, SR, SR; Moreno-Vinasco, L; Wang, L; Lang, GD; Natarajan, V; Garcia, JGN 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A1150 
English 
WOS:000208771000151 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
BACKGROUND: Particulate air pollution is known to be associated with cardiopulmonary morbidity and mortality. We recently demonstrated that particulate matter (PM) exposure triggers massive oxidative stress in endothelial cells (EC), further disrupting endothelial integrity and producing lung vascular hyperpermeability. Recently evidence has implicated that the endogenous gasotransmitter, hydrogen sulfide (H2S), in a very similar pattern as nitric oxide, exerts activity as a novel endothelial cell–derived relaxing factor (EDRF) and likely participates in endothelial functional regulation and protection.

OBJECTIVE: We hypothesize that H2S, an endogenous gaseous molecule in the circulation, protects against PM-induced endothelial barrier disruption and pulmonary inflammation.

METHODS: Changes in human lung EC monolayer permeability reflected by Transendothelial Electrical Resistance (TER) were measured. Reactive oxygen species (ROS) generation and murine pulmonary inflammatory responses were studied with the exposure to PM and NaSH, an accepted H2S donor.

RESULTS: Like the ROS scavenger N-acetyl cysteine (NAC, 5 mM), NaSH (10 µM) significantly reduces PM-induced ROS in EC and further inhibits oxidative activation of p38 MAP kinase, which induces stress fiber and paracellular gap formation in ECs. In parallel, we observed that NaSH (10 µM) activates Akt, which contributes to protect endothelial integrity against PM challenge. Both pathways contribute to the EC barrier integrity afforded by H2S in PM-induced EC barrier disruption. Furthermore, NaSH (20 mg/kg, intraperitoneal injection, 30 min pretreatment) reduced intratracheal PM challenge-induced vascular protein leak, inflammatory leukocyte infiltration, and proinflammatory cytokine release in a murine model.

CONCLUSIONS: These data suggest a protective role of H2S in vascular integrity, pulmonary inflammation and remodeling against PM, and provide the basis for the development of novel H2S-related therapeutic candidates for pulmonary inflammation. This study is supported by Environmental Protection Agency/Johns Hopkins Particulate Matter Center Grant # RD83241701 (JGNG) and NIH HL058064 (JGNG). 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010