title: Hydrogen sulfide attenuates particulate matter-induced human lung endothelial barrier disruption via combined reactive oxygen species scavenging and Akt activation.
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 (H(2)S), 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 H(2)S 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 H(2)S against PM-induced endothelial barrier dysfunction. Furthermore, NaSH (20 mg/kg) reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in bronchoalveolar lavage fluids in a murine model of PM-induced lung inflammation. These data suggest a potentially protective role for H(2)S in PM-induced inflammatory lung injury and vascular hyperpermeability.
authors.affiliation: Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.forename: Syed R
authors.initials: SR
authors.lastname: Zaidi
authors.forename: Saad
authors.initials: S
authors.lastname: Sammani
authors.forename: Jessica
authors.initials: J
authors.lastname: Siegler
authors.forename: Liliana
authors.initials: L
authors.lastname: Moreno-Vinasco
authors.forename: Biji
authors.initials: B
authors.lastname: Mathew
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Natarajan
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D002478:Cells, Cultured; D017097:Electric Impedance; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D055806:Microvessels / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D052638:Particulate Matter / Q000633:toxicity*; D010766:Phosphorylation; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D006862:Hydrogen Sulfide