Cell-cell interactions and bronchoconstrictor eicosanoid reduction with inhaled carbon monoxide and resolvin D1 (original) (raw)

2014, AJP: Lung Cellular and Molecular Physiology

AM, Serhan CN. Cell-cell interactions and bronchoconstrictor eicosanoid reduction with inhaled carbon monoxide and resolvin D1. 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 PMNplatelet aggregates, reducing leukotrienes (LTs) and thromboxane B 2 (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 PMNplatelet 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. ischemia/reperfusion; resolvins; lung; transcellular eicosanoid biosynthesis; leukotrienes; thromboxane CARBON MONOXIDE (CO) that is produced locally via the hemoxygenase system has emerged as an endogenous gasotransmitter that possesses physiological roles in cardiovascular, immune, and nervous systems (22). Inhaled low-dose CO evokes anti-inflammatory responses both in vivo and in vitro * M. Shinohara and M. Kibi are co-first authors.