Now an international team of scientists with participation from Vienna has identified a key factor in the immune messenger Fas ligand for severe disease progression and lung damage. FasL on immune cells drives lung cells to commit suicide.
“The dysregulated immune response and the inflammatory mechanisms that lead to severe Covid-19 disease are still not fully understood. We recently identified misdirected cell death caused by ligands (binding proteins of receptors; note) as the cause of fatal inflammation “We have hypothesized that this process could also cause or contribute to the pathological inflammation and lung failure following a SARS-CoV-2 infection,” wrote Marie-Christine Albert (University of Cologne) and her co-authors them Roman Reindl-Schwaighofer from the University Clinic for Internal Medicine III in Vienna (MedUni/AKH), in “Cell Death & Differentiation” (
Tested on mice
First of all, the scientists developed a new animal model (MA20) with mice, which could be used to track the important disease processes of Covid-19. To do this, the experts used a SARS-Cov-2 virus strain with a mutation that caused the pathogen to have a stronger affinity for the ACE2 receptors in mice. ACE2 receptors are the entry point for SARS-CoV-2 into cells. In series experiments with 20 infections of new animals each time, a virus was bred that caused severe to fatal illnesses in the animals.
Finally, young and old mice from a known laboratory strain were infected. “Simultaneously with the occurrence of cell death and inflammation, the expression of FasL (Fas ligands) on monocytic macrophages and NK cells (“phagocytes” and so-called natural killer cells; note) increased in the mice infected with MA20,” they wrote Scientist. FasL is essentially an immune messenger. If FasL binds to cells with the corresponding receptor (Fas), this means a signal that triggers programmed cell death (apoptosis), a type of cell suicide. Normally, this mechanism serves to eliminate unnecessary and possibly harmful cells in mammals and humans. However, this usually doesn’t work with cancer cells.
Life rate dramatically increased
The scientists reversed the matter. They blocked FasL in mice infected with SARS-CoV-2. The result: This treatment dramatically increased the animals’ life rate, for example from 40 to 90 percent in older mice. “Therapeutic blockade of FasL reduces cell death and inflammation in the lungs of MA20-infected mice,” the scientists noted. Apparently, immune cells with a particularly strong production of Fas ligands are responsible for the often fatal lung complications – caused by severe tissue damage as a result of cell death – in the context of Covid-19 diseases.
The highlight, according to the authors of the study: “FasL is also increasingly present in lung lavage fluid (fluid from samples taken for diagnostic purposes; note) from Covid-19 patients in a critical stage of the disease. Overall, the research results identify FasL as a determining factor (in those affected; note) the pathogenic immune response that causes the severity and lethality of Covid-19. This implies that patients with severe Covid-19 disease could benefit from a blockade of FasL as a treatment.”
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