Cell-Cell interactions and bronchoconstrictor eicosanoid reduction with inhaled carbon monoxide and resolvin D1

Masakazu Shinohara, Megumi Kibi, Ian R. Riley, Nan Chiang, Jesmond Dalli, Bryan D. Kraft, Claude A. Piantadosi, Augustine M.K. Choi, Charles N. Serhan

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)L746-L757
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number10
StatePublished - Nov 15 2014


  • Ischemia/reperfusion
  • Leukotrienes
  • Lung
  • Resolvins
  • Thromboxane
  • Transcellular eicosanoid biosynthesis

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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