AUTHOR=Huang Yumeng , Ji Qian , Zhu Yanyan , Fu Shengqiao , Chen Shuangwei , Chu Liangmei , Ren Yongfei , Wang Yue , Lei Xuan , Gu Jia , Tai Ningzheng , Liu Dadong 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 9 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.777989

DOI=10.3389/fcell.2021.777989

ISSN=2296-634X

ABSTRACT=Excessive Neutrophils extracellular traps (NETs) formation is an important contributor to sepsis induced acute lung injury (ALI). Recent reports indicate that platelets can induce neutrophils extracellular traps formation. However, the specific mechanism remains unclear. Tph1 gene, which encodes the rate-limiting enzyme for peripheral 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 NETs formation in lung tissues, alleviated sepsis induced lung inflammatory injury, and reduced the mortality rate of CLP mice. Further study showed that a mass of the accumulation of platelets and NETs in the lung of septic mice, and peripheral 5-HT deficiency reduced this accumulation. In vitro studies, we found that platelets from wild type (WT) mice could promote LPS-induced NETs formation, while platelets derived from Tph1-/- mice could not. Exogenous 5-HT intervention increased LPS-induced NETs formation when Tph1-/- platelets were co-cultured with WT neutrophils. Therefore, our study uncovers a mechanism by which peripheral 5-HT aggravated sepsis-induced ALI by promoting NETs formation in lung of septic mice.