Systemic vasoprotection by inhaled carbon monoxide is mediated through prolonged alterations in monocyte/macrophage function

Publication date: Available online 5 October 2019Source: Nitric OxideAuthor(s): Andrew Leake, Karim Salem, Michael C. Madigan, Ghee Rye Lee, Ankur Shukla, Guiying Hong, Brian S. Zuckerbraun, Edith TzengAbstractCarbon 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 ...
Source: Nitric Oxide - Category: Chemistry Source Type: research