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Mitochondria-Derived Damage-Associated Molecular Patterns in Sepsis: From Bench to Bedside.

ABSTRACT: Sepsis is one of the most serious health hazards. Current research suggests that the pathogenesis of sepsis is mediated by both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Mitochondria are among the most important organelles in cells and determine their life and death. A variety of mitochondria-derived DAMPs (mtDAMPs) are similar to bacteria because mitochondria are derived from bacteria according to the mitochondrial endosymbiotic theory. Their activated signaling pathways extensively affect organ functions, the immune system, and metabolic functions in sepsis. In this review, we describe the essential roles of mtDAMPs in sepsis and discuss their research prospects and clinical importance.

SUBMITTER: Li S

PROVIDER: S-EPMC6530230 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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Mitochondria-Derived Damage-Associated Molecular Patterns in Sepsis: From Bench to Bedside.

Li Sicheng S Hu Qiongyuan Q Huang Jinjian J Wu Xiuwen X Ren Jianan J Ren Jianan J

Oxidative medicine and cellular longevity 20190508

Sepsis is one of the most serious health hazards. Current research suggests that the pathogenesis of sepsis is mediated by both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Mitochondria are among the most important organelles in cells and determine their life and death. A variety of mitochondria-derived DAMPs (mtDAMPs) are similar to bacteria because mitochondria are derived from bacteria according to the mitochondrial endosymbiotic theory. The ...[more]

PMID: 31205588

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Project description:Inflammation is an essential process of the host defense against infections, illness, or tissue injuries. However, unregulated inflammation has been associated with chronic inflammatory autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and atherosclerosis. Polymorphonuclear neutrophils (PMNL) are amongst the first immune cells involved in the acute inflammatory response used to fight bacterial infections. Once activated, PMNL releases inflammatory mediators, enzymes and large quantities of microparticles in the extracellular milieu to recruit various immune cells required to fight the invading pathogens. Recent evidence also shows that platelets (PLTs), well known for their coagulation proprieties, are also implicated in the body’s inflammatory response. Interestingly, activated PLTs can release fully functional mitochondria in the extracellular milieu. Known as the powerhouse of the cell, the mitochondria share similar characteristics with bacteria. Therefore, we hypothesize that PLTs-derived mitochondria present in the extracellular milieu, acting in a similar way as bacteria, induce a sterile inflammatory response that involves the PMNL. The objective of this study was to investigate the sterile inflammatory response of PMNL caused by the exposure to PLTs-derived extracellular mitochondria. Blood was obtained from healthy consenting donors, then PMNL and PLTs-derived mitochondria were isolated and purified. Following the co-incubation of PMNL with various physiological doses of PLTs-derived mitochondria, a characterization of the interaction between PMNL and PLTs-derived mitochondria and an investigation of the inflammatory proprieties of PMNL were performed using flow cytometry, transmission electron microscopy, and high-resolution respirometry. While the transcriptomic analysis indicated that several mitochondrial genes had increased expression, no mitochondrial-dependent increase in oxygen consumption was observed by high-resolution respirometry experiments. However, our data show that PLTs-derived mitochondria significantly induce, in a dose-dependent manner, the release of PMNL microparticles. This study provides new insight into the role of PLTs-derived mitochondria in the context of sterile inflammation.

Dataset Information

Mitochondria-Derived Damage-Associated Molecular Patterns in Sepsis: From Bench to Bedside.

Publications

Mitochondria-Derived Damage-Associated Molecular Patterns in Sepsis: From Bench to Bedside.

Similar Datasets

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