Treatment of "bad" inflammation
As a result of injury, the contents of mitochondria are released from damaged cells – a group of proteins with the common name N-formyl peptides, which trigger a potentially deadly immune response of the body. A group of researchers from the Medical College of Georgia at Augusta University (Medical College of Georgia at Augusta University) have developed and tested on animal models and human cell culture a drug that is capable of cleaving N-formyl peptides. It reduces the effusion of fluid from blood vessels into tissues, reduces the systemic inflammatory response and increases the survival of patients after injury.
N-formyl peptides are synthesized in mitochondria and are involved in the energy production process. Normally, mitochondria are able to cut off the formyl group, neutralizing proteins before they leave it. In case of injury, a large amount of N-formyl peptides is released.
The formyl group is part of all 13 proteins that are synthesized in mitochondria, as well as proteins of bacterial origin. This confirms the hypothesis that mitochondria were previously bacteria, and when their contents are released, the body reacts to it as an infection. Scientists believe that the formyl group is a trigger that triggers a systemic inflammatory reaction in both massive infection (sepsis) and trauma.
In previous animal studies, it has been proven that proteins with a formyl group cause relaxation of smooth muscles and increased vascular permeability. As a result, a state of shock develops, accompanied by a sharp (two-thirds) drop in blood pressure due to a decrease in the volume of circulating blood.
The enzyme deformylase cleaves the formyl (CHO) group from N-formyl peptides, thus neutralizing them. Researchers have suggested that deformylase can be used to reduce the immune response due to injury or infection.
To do this, the researchers created a mouse model of sepsis, and also incubated human endothelial cells lining the aorta with blood plasma rich in N-formyl peptides. Deformylase increased the survival rate of mice with sepsis by 28% and preserved tight contacts between endothelial cells (cell divergence leads to increased vascular wall permeability and edema).
The deformylase used in the study has a very short half-life. The authors are working to modify the drug, making it more stable, and prolong its effect in the body. This will allow the use of deformylase not only in open injuries (irrigation with a solution), but also in closed injuries and even cancers accompanied by tissue decay.
The determination of mitochondrial DNA and N-formyl peptides in the blood can be used as a diagnostic test and a criterion for the effectiveness of treatment of generalized inflammation.
The study was reported at the 41st Annual Conference of the Society for the Study of Shock in Arizona, which was held on June 9-12, 2018.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru According to Augusta University: Drug may quell deadly immune response when trauma spills the contents of our cells' powerhouses.