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

M Shinohara, M Kibi, IR Riley… - … of Physiology-Lung …, 2014 - journals.physiology.org
M Shinohara, M Kibi, IR Riley, N Chiang, J Dalli, BD Kraft, CA Piantadosi, AMK Choi…
American Journal of Physiology-Lung Cellular and Molecular …, 2014journals.physiology.org
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 …
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.
American Physiological Society