Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data

Mohammed Toufiq, Jessica Roelands, Mohamed Alfaki, Basirudeen Syed Ahamed Kabeer, Marwa Saadaoui, Arun Prasath Lakshmanan, Dhinoth Kumar Bangarusamy, Selvasankar Murugesan, Davide Bedognetti, Wouter Hendrickx, Souhaila Al Khodor, Annalisa Terranegra, Darawan Rinchai, Damien Chaussabel, Mathieu Garand

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations

Abstract

According to publicly available transcriptome datasets, the abundance of Annexin A3 (ANXA3) is robustly increased during the course of sepsis; however, no studies have examined the biological significance or clinical relevance of ANXA3 in this pathology. Here we explored this interpretation gap and identified possible directions for future research. Based on reference transcriptome datasets, we found that ANXA3 expression is restricted to neutrophils, is upregulated in vitro after exposure to plasma obtained from septic patients, and is associated with adverse clinical outcomes. Secondly, an increase in ANXA3 transcript abundance was also observed in vivo, in the blood of septic patients in multiple independent studies. ANXA3 is known to mediate calcium-dependent granules–phagosome fusion in support of microbicidal activity in neutrophils. More recent work has also shown that ANXA3 enhances proliferation and survival of tumour cells via a Caspase-3-dependent mechanism. And this same molecule is also known to play a critical role in regulation of apoptotic events in neutrophils. Thus, we posit that during sepsis ANXA3 might either play a beneficial role, by facilitating microbial clearance and resolution of the infection; or a detrimental role, by prolonging neutrophil survival, which is known to contribute to sepsis-mediated organ damage.

Original languageEnglish
Pages (from-to)291-302
Number of pages12
JournalImmunology
Volume161
Issue number4
DOIs
StatePublished - Dec 2020

Keywords

  • annexin
  • bacteremia
  • cell proliferation
  • endotoxemia
  • immunity
  • inflammation
  • neutrophil
  • sepsis
  • transcriptome

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