Cell-cell interactions and bronchoconstrictor eicosanoid reduction with inhaled carbon monoxide and resolvin D1.
Am J Physiol Lung Cell Mol Physiol
; 307(10): L746-57, 2014 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-25217660
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tromboxano B2
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Monóxido de Carbono
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Comunicação Celular
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Ácidos Docosa-Hexaenoicos
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Leucotrienos
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Lesão Pulmonar Aguda
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Pulmão
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Antimetabólitos
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article