Particulate matter disrupts human lung endothelial barrier integrity via ROS- and p38 MAPK-dependent pathways

Ting Wang, Eddie T. Chiang, Liliana Moreno-Vinasco, Gabriel D. Lang, Srikanth Pendyala, Jonathan M. Samet, Alison S. Geyh, Patrick N. Breysse, Steven N. Chillrud, Viswanathan Natarajan, Joe G.N. Garcia

Research output: Contribution to journalArticlepeer-review

90 Scopus citations


Epidemiologic studies have linked exposure to airborne pollutant particulate matter (PM) with increased cardiopulmonary mortality and morbidity. The mechanisms of PM-mediated lung pathophysiology, however, remain unknown. We tested the hypothesis that PM, via enhanced oxidative stress, disrupts lung endothelial cell (EC) barrier integrity, thereby enhancing organ dysfunction. Using PM collected from Ft. McHenry Tunnel (Baltimore, MD), we assessed PM-mediated changes in transendothelial electrical resistance (TER) (a highly sensitive measure of barrier function), reactive oxygen species (ROS) generation, and p38 mitogen-activated protein kinase (MAPK) activation in human pulmonary artery EC. PM induced significant dose (10-100 μg/ml)- and time (0-10 h)-dependent EC barrier disruption reflected by reduced TER values. Exposure of human lung EC to PM resulted in significant ROS generation, which was directly involved in PM-mediated EC barrier dysfunction, as N-acetyl-cysteine (NAC, 5 mM) pretreatment abolished both ROS production and barrier disruption induced by PM. Furthermore, PM induced p38 MAPK activation and HSP27 phosphorylation, events that were both attenuated by NAC. In addition, PM-induced EC barrier disruption was partially prevented by the p38 MAP kinase inhibitor SB203580 (10 μM) as well as by reduced expression of either p38MAPK β or HSP27 (siRNA). These results demonstrate that PM induces ROS generation in human lung endothelium, resulting in oxidative stress-mediated EC barrier disruption via p38 MAPK- and HSP27-dependent pathways. These findings support a novel mechanism for PM-induced lung dysfunction and adverse cardiopulmonary outcomes.

Original languageEnglish (US)
Pages (from-to)442-449
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Issue number4
StatePublished - Apr 1 2010


  • Endothelial permeability
  • HSP27
  • Particulate matter
  • ROS
  • p38 MAP kinase

ASJC Scopus subject areas

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


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