Activated Platelets Autocrine 5-Hydroxytryptophan Aggravates Sepsis-Induced Acute Lung Injury by Promoting Neutrophils Extracellular Traps Formation

• Published in: Frontiers in cell and developmental biology Vol. 9; p. 777989
• Main Authors: Huang, Yumeng, Ji, Qian, Zhu, Yanyan, Fu, Shengqiao, Chen, Shuangwei, Chu, Liangmei, Ren, Yongfei, Wang, Yue, Lei, Xuan, Gu, Jia, Tai, Ningzheng, Liu, Dadong
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17.01.2022
• Subjects: 5-hydroxytryptophan (5-HT); acute lung injury (ALI); Cell and Developmental Biology; neutrophil; neutrophil extracellular traps (NETs); platelet; sepsis; neutrophil extracellular traps (NETs); platelet; 5-hydroxytryptophan (5-HT); neutrophil; sepsis; acute lung injury (ALI)
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2021.777989

Excessive neutrophil extracellular trap (NET) formation is an important contributor to sepsis-induced acute lung injury (ALI). Recent reports indicate that platelets can induce neutrophil extracellular trap formation. However, the specific mechanism remains unclear. gene, which encodes the rate-limiting enzyme for peripheral 5-hydroxytryptophan (5-HT) synthesis, was knocked out in mice to simulate peripheral 5-HT deficiency. Cecal ligation and puncture (CLP) surgery was performed to induce sepsis. We found that peripheral 5-HT deficiency reduced NET formation in lung tissues, alleviated sepsis-induced lung inflammatory injury, and reduced the mortality rate of CLP mice. In addition, peripheral 5-HT deficiency was shown to reduce the accumulation of platelets and NETs in the lung of septic mice. We found that platelets from wild-type (WT), but not knockout ( ), mice promote lipopolysaccharide (LPS)-induced NET formation. Exogenous 5-HT intervention increased LPS-induced NET formation when platelets were co-cultured with WT neutrophils. Therefore, our study uncovers a mechanism by which peripheral 5-HT aggravated sepsis-induced ALI by promoting NET formation in the lung of septic mice.