Cell-Cell interactions and bronchoconstrictor eicosanoid reduction with inhaled carbon monoxide and resolvin D1 Academic Article uri icon


MeSH Major

  • Acute Lung Injury
  • Antimetabolites
  • Carbon Monoxide
  • Cell Communication
  • Docosahexaenoic Acids
  • Leukotrienes
  • Lung
  • Thromboxane B2


  • Polymorphonuclear leukocyte (PMN)-mediated acute lung injury from ischemia/reperfusion (I/R) remains a major cause of morbidity and mortality in critical care medicine. Here, we report that inhaled low-dose carbon monoxide (CO) and intravenous resolvin D1 (RvD1) in mice each reduced PMN-mediated acute lung injury from I/R. Inhaled CO (125-250 ppm) and RvD1 (250-500 ng) each reduced PMN lung infiltration and gave additive lung protection. In mouse whole blood, CO and RvD1 attenuated PMN-platelet aggregates, reducing leukotrienes (LTs) and thromboxane B2 (TxB2) in I/R lungs. With human whole blood, CO (125-250 ppm) decreased PMN-platelet aggregates, expression of adhesion molecules, and cysteinyl LTs, as well as TxB2. RvD1 (1-100 nM) also dose dependently reduced platelet activating factor-stimulated PMN-platelet aggregates in human whole blood. In nonhuman primate (baboon) lung infection with Streptococcus pneumoniae, inhaled CO reduced urinary cysteinyl LTs. These results demonstrate lung protection by low-dose inhaled CO as well as RvD1 that each reduced PMN-mediated acute tissue injury, PMN-platelet interactions, and production of both cysteinyl LTs and TxB2. Together they suggest a potential therapeutic role of low-dose inhaled CO in organ protection, as demonstrated using mouse I/R-initiated lung injury, baboon infections, and human whole blood.

publication date

  • January 2014



  • Academic Article



  • eng

PubMed Central ID

  • PMC4233292

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00166.2014

PubMed ID

  • 25217660

Additional Document Info

start page

  • L746

end page

  • 57


  • 307


  • 10