DNA extracellular traps as potential biomarker of chronic haemophilic synovitis and therapeutic perspective in patients treated with PRP: A pilot study.

INTRODUCTION: Hemarthrosis causes chronic haemophilic synovitis (CHS). Although neutrophils are major immune cells infiltrating joints after bleeding, their role on the pathogenesis of CHS is unknown. Neutrophils release extracellular DNA traps (ETs), structures of DNA with bound granular enzymes that were associated with tissue damage. AIMS: To evaluate the presence of ETs as pathogenic biomarker and the protective effect of intraarticular injection of platelet-rich plasma (PRP) in patients with CHS. METHODS: Haemophilia Joint Health Score (HJHS) and bleeding episodes (BE) were measured and correlated with ETs indicators (DNA/DNA-Elastase) in synovial fluids (SF), PRP and plasma of 21 patients. RESULTS: Soluble DNA and DNA-Elastase were detected in SF and plasma of patients. The synovial and plasma levels of DNA-Elastase positively correlated with worse HJHS/BE. Interestingly, remaining ETs-inducer factors were present in SF that induced the in vitro release of ETs from blood-isolated neutrophils. This phenomenon was impaired by adding plasma or PRP. Finally, preliminary data obtained from five patients indicate that levels of DNA-Elastase and HJHS/BE decreased after receiving intraarticular injection of PRP. CONCLUSIONS: The synovial and plasma levels of DNA-Elastase correlated with worse HJHS/BE suggesting that ETs formation could be a biomarker and potential therapeutic target for CHS. The intraarticular injection of PRP underlined a new potential alternative therapy, decreasing ETs formation in synovia of patients with CHS. However, our hypotheses must be confirmed in the future with better designed and more statistical power studies. Meanwhile, the use of intraarticular injections of PRP for the treatment of CHS remains controversial.

Reactive oxygen species are involved in eosinophil extracellular traps release and in airway inflammation in asthma.

In asthma, there are high levels of inflammatory mediators, reactive oxygen species (ROS), and eosinophil extracellular traps (EETs) formation in airway. Here, we attempted to investigate the ROS involvement in EETs release and airway inflammation in OVA-challenged mice. Before the intranasal challenge with ovalbumin (OVA), animals were treated with two ROS inhibitors, N-acetylcysteine (NAC) or diphenyleneiodonium (DPI). We showed that NAC treatment reduced inflammatory cells in lung. DPI and NAC treatments reduced eosinophil peroxidase (EPO), goblet cells hyperplasia, proinflammatory cytokines, NFκB p65 immunocontent, and oxidative stress in lung. However, only the NAC treatment improved mitochondrial energy metabolism. Moreover, the treatments with DPI and NAC reduced EETs release in airway. This is the first study to show that ROS are needed for EETs formation in asthma. Based on our results, NAC and DPI treatments can be an interesting alternative for reducing airway inflammation, mitochondrial damage, and EETs release in asthma.

Chick heterophils release DNA extracellular traps (DETs) in vitro and in vivo upon Aspergillus fumigatus conidia exposure.

Aspergillosis is a common fungal disease in avian species, causing high mortality in young chicks in agricultural farms and yards. It is caused by fungi belonging to the genus Aspergillus. Aspergillosis occurs by inhalation of fungal conidia, and in chickens, effective infection control relies on a rapid and large influx of heterophils to the lungs. Heterophils, upon different stimuli, release to the extracellular milieu their chromatin associated with several proteins that ensnare and kill different pathogens similarly to neutrophil extracellular traps. Here, we showed that Aspergillus fumigatus conidia and the peptidogalactomannan (PGM), isolated from the fungus cell wall, induce the release of DNA extracellular traps (DETs) in chicks' blood and lung heterophils. We demonstrated that reactive oxygen species, elastase and peptidyl arginine deiminase (PAD) were involved in DETs extrusion, the occurrence of DETs in the lungs of A. fumigatus-exposed chicks in vivo, and its role in chick survival. These results may contribute to developing more efficient tools for the therapeutic and diagnosis of aspergillosis.