Ohm, I have read that a large portion of extra
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Posted On: 10/10/2020 9:30:06 AM
Ohm,
I have read that a large portion of extra cellular atp is from activated platelets. I am far from understanding the clotting cascade. How does CCR5 blockade prevent increased extracelluar ATP? What should I read?
Interesting article noted the profound inflammatory effects of extracellular ATP, but also that blockade of atp with suramin (recently suggested as a solution to cytokine storm) did not reduce mortality or morbidity.
https://www.nature.com/articles/cddis201470
“Extracellular ATP drives systemic inflammation, tissue damage and mortality“
“ n this paper, we suggest an important pro-inflammatory and toxic role for extracellular ATP, which is not restricted to inflammasome activation. We found that removal of extracellular ATP by apyrase treatment not only prevented systemic IL-1β accumulation but also precluded the induction of inflammasome-independent cytokines, such as TNF and IL-10, of mitochondrial damage, cellular disintegration, apoptotic death, intestinal injury and barrier breakdown, and subsequent mortality, in a murine model of LPS-induced shock.”
And
“ When given as a pre-treatment, suramin efficiently prevented LPS-induced TNF production, leukocyte infiltration and necrotic tissue damage (Figures 4a–c). Nevertheless, suramin could not prevent IL-1β production (Figure 4d) or protect against mortality (Figure 4e). Surprisingly, when given as a post-treatment, suramin even accelerated mortality (Figure 4e), which was accompanied by increased levels of circulating TNF and IL-1β, as well as evidence of early tissue damage and exacerbated neutrophil infiltration (Figures 4d and f–h).”
I have read that a large portion of extra cellular atp is from activated platelets. I am far from understanding the clotting cascade. How does CCR5 blockade prevent increased extracelluar ATP? What should I read?
Interesting article noted the profound inflammatory effects of extracellular ATP, but also that blockade of atp with suramin (recently suggested as a solution to cytokine storm) did not reduce mortality or morbidity.
https://www.nature.com/articles/cddis201470
“Extracellular ATP drives systemic inflammation, tissue damage and mortality“
“ n this paper, we suggest an important pro-inflammatory and toxic role for extracellular ATP, which is not restricted to inflammasome activation. We found that removal of extracellular ATP by apyrase treatment not only prevented systemic IL-1β accumulation but also precluded the induction of inflammasome-independent cytokines, such as TNF and IL-10, of mitochondrial damage, cellular disintegration, apoptotic death, intestinal injury and barrier breakdown, and subsequent mortality, in a murine model of LPS-induced shock.”
And
“ When given as a pre-treatment, suramin efficiently prevented LPS-induced TNF production, leukocyte infiltration and necrotic tissue damage (Figures 4a–c). Nevertheless, suramin could not prevent IL-1β production (Figure 4d) or protect against mortality (Figure 4e). Surprisingly, when given as a post-treatment, suramin even accelerated mortality (Figure 4e), which was accompanied by increased levels of circulating TNF and IL-1β, as well as evidence of early tissue damage and exacerbated neutrophil infiltration (Figures 4d and f–h).”
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