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Scientists have discovered a new mechanism that could help explain why other people sick with covid develop life-threatening systemic inflammation, according to a study. Researchers at the University of Sao Paulo (USP) in Brazil have discovered that El 19 is linked to an imbalance in a vital signaling pathway of the immune system. (Also read: Daily Covid cases in China are the highest since the pandemic began)
The researchers detected a “dysregulation,” or dysfunctional regulation, of the immune formula mediated by adenosine triphosphate (ATP), one of the sources of power for cellular processes.
Patients with severe COVID-19 had higher levels of ATP in their blood and lower levels of adenosine, which are expected to build up when ATP is metabolized for energy production, according to the study.
“The immune formula includes several signaling pathways that provide alerts in reaction to the invasion of a pathogen, for example. One comes to ATP, which triggers the release of inflammatory ingredients into defense cells to attack the invader,” said researcher Maria Notomi Sato.
“The immune formula also has mechanisms to prevent excessive inflammation, but when this error in ATP metabolism occurs, it leads to massive imbalance and formulated dysfunctions in the immune response,” Sato said.
The buildup of unmetabolized ATP, according to the study, produces a pro-inflammatory state and triggers a life-threatening systemic inflammation known as cytokine storm.
“An imbalance in the signaling formula and a disorder in the regulation of those components were highlighted, as one more thing in the formulaic point that attacks the organs of patients with severe COVID-19,” Sato said.
ATP is produced through cells and degraded in the extracellular environment through enzymes called ectonucleotidases.
“ATP becomes a danger signal when it leaves cells in gigantic quantities. When does this happen? When an exacerbated inflammatory reaction is activated, when cells are severely injured or when severe damage occurs,” said Anna Julia Pietrobon, co-author of the study. . Author of the article.
“In response, ATP triggers an inflammatory process that reaches other cells in a chain reaction,” Pietrobon said.
For the study, researchers measured ATP and adenosine levels in blood samples taken in 2020-21 from 88 patients with severe COVID-19. None of them had been vaccinated.
“We found that PTA-cleave-cleaving motile ectonucleotidases are less expressed in the mobiles of patients with mild and severe COVID-19, but in the latter. In fact, we concluded that the higher the ATP point, the more severe the disease. “says Pietrobon.
The researchers also studied imaginable alterations in the cells of the immune formula. “We found that some immune cells, namely B cells, expressed less CD39 and CD73, enzymes that break down ATP.
“Lymphocyte levels sometimes tend to be low in COVID-19 patients, but in our study, not only were B cell levels in the blood of critically ill patients low, but those cells also expressed lower amounts of either enzyme, contributing to less ATP metabolism and, therefore, less production of adenosine, the anti-inflammatory component that would verify this response,” Pietrobon said.
Faced with this discovery, the researchers tried to isolate the B cells that provide the blood samples and give them ATP.
“We conducted an in vivo experiment in which we gave ATP to cells from COVID-19 patients and healthy controls. The patients’ B cells produced less adenosine than those in healthy controls, in all likelihood because they expressed less CD39 and CD73,” he added. Said.
Researchers do not yet know whether the impaired ATP metabolism is due to or due to the exacerbated inflammatory reaction to SARS-CoV-2. They plan to investigate this in long-term projects, according to the study.
The link between severe COVID-19 and inflammasome activation is exacerbated and prevented after the infection clears.
The inflammasome is an internal protein complex of defense cells. When this cellular mechanism is activated, pro-inflammatory molecules, called cytokines, are produced to warn the immune formula that more defense cells want to be sent to the site of infection.
According to the researchers who conducted the ATP metabolism study, ATP accumulation along with low adenosine levels in critically ill patients could contribute to cytokine-mediated exacerbation of the inflammatory response.
“The inflammatory process triggered by inadequate ATP degradation occurs due to decompensation of this pathway, which functions as a form of anti-inflammatory regulation.
“However, when this error occurs in ATP-adenosine metabolism, ATP accumulation acts as a signal to other immune system inflammation pathways, for example, in inflammasome activation,” Sato said.
In those cases, where the regulation of the immune formula is dysfunctional, the exaggerated inflammatory reaction is directly similar to multi-organ failure and death.
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