Carbon monoxide confers protection in sepsis by enhancing Beclin 1-dependent autophagy and phagocytosis = 베클린-1 의존적인 오토페이지와 대식작용의 향상을 통해 패혈증 증가시 생체의 보호에 관여하는 일산화탄소

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Title
Carbon monoxide confers protection in sepsis by enhancing Beclin 1-dependent autophagy and phagocytosis = 베클린-1 의존적인 오토페이지와 대식작용의 향상을 통해 패혈증 증가시 생체의 보호에 관여하는 일산화탄소
Author(s)
S Lee; Seon-Jin Lee; A A Coronata; L E Fredenburgh; S W Chung; M A Perrella; K Nakahira; S W Ryter; A M K Choi
Bibliographic Citation
Antioxidants & Redox Signaling, vol. 20, no. 3, pp. 432-442
Publication Year
2014
Abstract
Aims: Sepsis, a systemic inflammatory response to infection, represents the leading cause of death in critically ill patients. However, the pathogenesis of sepsis remains incompletely understood. Carbon monoxide (CO), when administered at low physiologic doses, can modulate cell proliferation, apoptosis, and inflammation in pre-clinical tissue injury models, though its mechanism of action in sepsis remains unclear. Results: CO (250 ppm) inhalation increased the survival of C57BL/6J mice injured by cecal ligation and puncture (CLP) through the induction of autophagy, the down-regulation of pro-inflammatory cytokines, and by decreasing the levels of bacteria in blood and vital organs, such as the lung and liver. Mice deficient in the autophagic protein, Beclin 1 (Becn1 +/-) were more susceptible to CLP-induced sepsis, and unresponsive to CO therapy, relative to their corresponding wild-type (Becn1+/+) littermate mice. In contrast, mice deficient in autophagic protein microtubule-associated protein-1 light chain 3B (LC3B) (Map1lc3b-/-) and their corresponding wild-type (Map1lc3b+/+) mice showed no differences in survival or response to CO, during CLP-induced sepsis. CO enhanced bacterial phagocytosis in Becn1+/+ but not Becn1 +/- mice in vivo and in corresponding cultured macrophages. CO also enhanced Beclin 1-dependent induction of macrophage protein signaling lymphocyte-activation molecule, a regulator of phagocytosis. Innovation: Our findings demonstrate a novel protective effect of CO in sepsis, dependent on autophagy protein Beclin 1, in a murine model of CLP-induced polymicrobial sepsis. Conclusion: CO increases the survival of mice injured by CLP through systemic enhancement of autophagy and phagocytosis. Taken together, we suggest that CO gas may represent a novel therapy for patients with sepsis.
ISSN
1523-0864
Publisher
Mary Ann Liebert, Inc
DOI
http://dx.doi.org/10.1089/ars.2013.5368
Type
Article
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
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