TY - JOUR
T1 - Novel aspects of sepsis pathophysiology
T2 - NETs, plasma glycoproteins, endotheliopathy and COVID-19
AU - Nishibori, M.
N1 - Funding Information:
The author has been an advisor of the Japan Blood Products Organization and obtains the research support from the company.The author thank Ms. Mariko Yata for her help for preparing the manuscript. This work was supported in part by grants from JSPS KAKENHI grant Number JP19H03408 and from the Japan Agency for Medical Research and Development (AMED, 21lk0201085).
Funding Information:
The author thank Ms. Mariko Yata for her help for preparing the manuscript. This work was supported in part by grants from JSPS KAKENHI grant Number JP19H03408 and from the Japan Agency for Medical Research and Development (AMED , 21lk0201085 ).
Publisher Copyright:
© 2022 The Authors
PY - 2022/9
Y1 - 2022/9
N2 - In 2016, sepsis was newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis remains one of the crucial medical problems to be solved worldwide. Although the world health organization has made sepsis a global health priority, there remain no specific and effective therapy for sepsis so far. Indeed, over the previous decades almost all attempts to develop novel drugs have failed. This may be partly ascribable to the multifactorial complexity of the septic cascade and the resultant difficulties of identifying drug targets. In addition, there might still be missing links among dysregulated host responses in vital organs. In this review article, recent advances in understanding of the complex pathophysiology of sepsis are summarized, with a focus on neutrophil extracellular traps (NETs), the significant role of NETs in thrombosis/embolism, and the functional roles of plasma proteins, histidine-rich glycoprotein (HRG) and inter-alpha-inhibitor proteins (IAIPs). The specific plasma proteins that are markedly decreased in the acute phase of sepsis may play important roles in the regulation of blood cells, vascular endothelial cells and coagulation. The accumulating evidence may provide us with insights into a novel aspect of the pathophysiology of sepsis and septic ARDS, including that in COVID-19.
AB - In 2016, sepsis was newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis remains one of the crucial medical problems to be solved worldwide. Although the world health organization has made sepsis a global health priority, there remain no specific and effective therapy for sepsis so far. Indeed, over the previous decades almost all attempts to develop novel drugs have failed. This may be partly ascribable to the multifactorial complexity of the septic cascade and the resultant difficulties of identifying drug targets. In addition, there might still be missing links among dysregulated host responses in vital organs. In this review article, recent advances in understanding of the complex pathophysiology of sepsis are summarized, with a focus on neutrophil extracellular traps (NETs), the significant role of NETs in thrombosis/embolism, and the functional roles of plasma proteins, histidine-rich glycoprotein (HRG) and inter-alpha-inhibitor proteins (IAIPs). The specific plasma proteins that are markedly decreased in the acute phase of sepsis may play important roles in the regulation of blood cells, vascular endothelial cells and coagulation. The accumulating evidence may provide us with insights into a novel aspect of the pathophysiology of sepsis and septic ARDS, including that in COVID-19.
KW - COVID-19
KW - Endotheliopathy
KW - Histidine-rich glycoprotein (HRG)
KW - Neutrophil extracellular traps (NETs)
KW - Sepsis
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U2 - 10.1016/j.jphs.2022.06.001
DO - 10.1016/j.jphs.2022.06.001
M3 - Review article
C2 - 35926948
AN - SCOPUS:85132893351
VL - 150
SP - 9
EP - 20
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
SN - 1347-8648
IS - 1
ER -