TY - JOUR
T1 - Annexin A3 in sepsis
T2 - novel perspectives from an exploration of public transcriptome data
AU - Toufiq, Mohammed
AU - Roelands, Jessica
AU - Alfaki, Mohamed
AU - Syed Ahamed Kabeer, Basirudeen
AU - Saadaoui, Marwa
AU - Lakshmanan, Arun Prasath
AU - Bangarusamy, Dhinoth Kumar
AU - Murugesan, Selvasankar
AU - Bedognetti, Davide
AU - Hendrickx, Wouter
AU - Al Khodor, Souhaila
AU - Terranegra, Annalisa
AU - Rinchai, Darawan
AU - Chaussabel, Damien
AU - Garand, Mathieu
N1 - Funding Information:
This publication was made possible by NPRP grant # 10-0205-170348 from the Qatar National Research Fund (a member of Qatar Foundation). The work reported herein is solely the responsibility of the authors. Open Access funding was provided by the Qatar National Library.
Funding Information:
This publication was made possible by NPRP grant # 10‐0205‐170348 from the Qatar National Research Fund (a member of Qatar Foundation). The work reported herein is solely the responsibility of the authors. Open Access funding was provided by the Qatar National Library.
Publisher Copyright:
© 2020 The Authors. Immunology published by John Wiley & Sons Ltd
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - annexin
KW - bacteremia
KW - cell proliferation
KW - endotoxemia
KW - immunity
KW - inflammation
KW - neutrophil
KW - sepsis
KW - transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85090000764&partnerID=8YFLogxK
U2 - 10.1111/imm.13239
DO - 10.1111/imm.13239
M3 - Review article
C2 - 32682335
AN - SCOPUS:85090000764
SN - 0019-2805
VL - 161
SP - 291
EP - 302
JO - Immunology
JF - Immunology
IS - 4
ER -