Endotracheal intubation results in acute tracheal damage induced by mtDNA/TLR9/NF‐κB activity
Autor: | Michael M. Awad, Carlos A. Puyo, Alexander Earhart, Marin H. Kollef, Nicholas Staten, Colleen Haug, Oliver A. Prince |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Necrosis Neutrophils Swine Immunology Translational & Clinical Immunology mitochondrial DNA Pharmacology Biology Systemic inflammation DNA Mitochondrial Article Epithelium Proinflammatory cytokine Epithelial Damage 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tracheitis Cell Movement medicine Intubation Intratracheal Immunology and Allergy Animals Humans pain TLRs endotracheal intubation Pancreatic Elastase Organ dysfunction Interleukin-8 NF-kappa B TLR9 NF-κB Cell Biology medicine.disease Trachea 030104 developmental biology HEK293 Cells Phenotype chemistry 030220 oncology & carcinogenesis Toll-Like Receptor 9 Acute Disease Cytokines medicine.symptom Inflammation Mediators Reactive Oxygen Species |
Zdroj: | Journal of Leukocyte Biology |
ISSN: | 1938-3673 0741-5400 |
Popis: | Tracheitis secondary to placement of an endotracheal tube (ETT) is characterized by neutrophil accumulation in the tracheal lumen, which is generally associated with epithelial damage. Mitochondrial DNA (mtDNA), has been implicated in systemic inflammation and organ dysfunction following trauma; however, less is known about the effects of a foreign body on local trauma and tissue damage. We hypothesized that tracheal damage secondary to the ETT will result in local release of mtDNA at sufficient levels to induce TLR9 and NF‐κB activation. In a swine model we compared the differences between uncoated, and chloroquine (CQ) and N‐acetylcysteine (NAC) coated ETTs as measured by tracheal lavage fluids (TLF) over a period of 6 h. The swine model allowed us to recreate human conditions. ETT presence was characterized by neutrophil activation, necrosis, and release of proinflammatory cytokines mediated by TLR9/NF‐κB induction. Amelioration of the tracheal damage was observed in the CQ and NAC coated ETT group as shown in tracheal tissue specimens and TLF. The role of TLR9/NF‐κB dependent activity was confirmed by HEK‐Blue hTLR9 reporter cell line analysis after coincubation with TLF specimens with predetermined concentrations of NAC or CQ alone or TLR9 inhibitory oligodeoxynucleotide (iODN). These findings indicate that therapeutic interventions aimed at preventing mtDNA/TLR9/NF‐κB activity may have benefits in prevention of acute tracheal damage. Interaction between a foreign body and the trachea, as mediated by the innate immune system. |
Databáze: | OpenAIRE |
Externí odkaz: |