Systemic vasoprotection by inhaled carbon monoxide is mediated through prolonged alterations in monocyte/macrophage function.
Nitric Oxide
; 94: 36-47, 2020 01 01.
Article
in En
| MEDLINE
| ID: mdl-31593762
ABSTRACT
Carbon monoxide (CO) is anti-inflammatory and protective in models of disease. Its actions in vitro are short-lived but are sustained in vivo. We hypothesize that systemic CO can mediate prolonged phenotype changes in vivo, with a focus on macrophages (Mφs). Mφs isolated from CO treated rats responded to lipopolysaccharide (LPS) with increased IL6, IL10 and iNOS expression but decreased TNF. Conditioned media (CM) collected from peritoneal Mφs isolated from CO treated rats stimulated endothelial cell (EC) proliferation versus CM from Mφs from air treated rats. This effect was mediated by Mφ released VEGF and HMGB1. Inhaled CO reduced LPS induced Mφ M1 inflammatory phenotype for up to 5 days. Mitochondrial oxygen consumption in LPS treated Mφs from CO treated mice was preserved compared to LPS treated Mφs from control mice. Finally, transient reduction of inflammatory cells at the time of inhaled CO treatment eliminated the vasoprotective effect of CO in a rodent carotid injury model. Thus, inhaled CO induces a prolonged mixed phenotype change in Mφs, and potentially other inflammatory cells, that contribute to vasoprotection. These findings demonstrate the ability of inhaled CO to modify Mφs in a sustained manner to mediate its therapeutic actions, supporting the translational potential of inhaled CO.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carbon Monoxide
/
Monocytes
/
Anti-Inflammatory Agents, Non-Steroidal
/
Protective Agents
/
Inflammation
/
Macrophages
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Nitric Oxide
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2020
Document type:
Article
Affiliation country: