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Can I read Inhibition of transcription factor NFAT activity in activated platelets enhances their aggregation and exacerbates gram-negative bacterial septicemia on EtoBox?
Inhibition of transcription factor NFAT activity in activated platelets enhances their aggregation and exacerbates gram-negative bacterial septicemia by Valentina Poli; Marco Di Gioia; Martha Sola-Visner; Francesca Granucci; Andrew L. Frelinger; Alan D. Michelson; Ivan Zanoni is a Immunology and Microbiology article available to read on EtoBox.
What is Inhibition of transcription factor NFAT activity in activated platelets enhances their aggregation and exacerbates gram-negative bacterial septicemia about?
During gram-negative septicemia, interactions between platelets and neutrophils initiate a detrimental feedback loop that sustains neutrophil extracellular trap (NET) induction, disseminated intravascular coagulation, and inflammation. Understanding intracellular pathways that control platelet-neutrophil interactions is essential for identifying new therapeutic targets. Here, we found that thrombin signaling induced activation of the transcription factor NFAT in platelets. Using genetic and pharmacologic approaches, as well as iNFATuation, a newly developed mouse model in which NFAT activation can be abrogated in a cell-specific manner, we demonstrated that NFAT inhibition in activated murine and human platelets enhanced their activation and aggregation, as well as their interactions with neutrophils and NET induction. During gram-negative septicemia, NFAT inhibition in platelets promoted disease severity by increasing disseminated coagulation and NETosis. NFAT inhibition also partially restored coagulation ex vivo in patients with hypoactive platelets. Our results define non-transcriptional roles for NFAT that could be harnessed to address pressing clinical needs.
Who reads Inhibition of transcription factor NFAT activity in activated platelets enhances their aggregation and exacerbates gram-negative bacterial septicemia?
It is typically read by researchers, students, and practitioners in Immunology and Microbiology.
- Author
- Valentina Poli; Marco Di Gioia; Martha Sola-Visner; Francesca Granucci; Andrew L. Frelinger; Alan D. Michelson; Ivan Zanoni
- Publisher
- Elsevier BV
- Published
- 2022
- Language
- EN
- Field
- Immunology and Microbiology (Life Sciences)