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

Journal Article (Clinical Trial;Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Shinohara, M; Kibi, M; Riley, IR; Chiang, N; Dalli, J; Kraft, BD; Piantadosi, CA; Choi, AMK; Serhan, CN

Published Date

  • November 15, 2014

Published In

Volume / Issue

  • 307 / 10

Start / End Page

  • L746 - L757

PubMed ID

  • 25217660

Pubmed Central ID

  • PMC4233292

Electronic International Standard Serial Number (EISSN)

  • 1522-1504

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00166.2014


  • eng

Conference Location

  • United States