Activated Platelets Autocrine 5-Hydroxytryptophan Aggravates Sepsis-Induced Acute Lung Injury by Promoting Neutrophils Extracellular Traps Formation
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. Tph1 gene, which encodes the rate...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.777989/full |
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| author | Yumeng Huang Qian Ji Yanyan Zhu Shengqiao Fu Shuangwei Chen Liangmei Chu Yongfei Ren Yue Wang Xuan Lei Jia Gu Ningzheng Tai Dadong Liu |
| author_facet | Yumeng Huang Qian Ji Yanyan Zhu Shengqiao Fu Shuangwei Chen Liangmei Chu Yongfei Ren Yue Wang Xuan Lei Jia Gu Ningzheng Tai Dadong Liu |
| author_sort | Yumeng Huang |
| collection | DOAJ |
| description | 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. Tph1 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 Tph1 knockout (Tph1−/−), mice promote lipopolysaccharide (LPS)-induced NET formation. Exogenous 5-HT intervention increased LPS-induced NET 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 NET formation in the lung of septic mice. |
| first_indexed | 2024-12-21T01:02:35Z |
| format | Article |
| id | doaj.art-6f824d9d771446a69c567434fe8cba84 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T01:02:35Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-6f824d9d771446a69c567434fe8cba842022-12-21T19:21:09ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.777989777989Activated Platelets Autocrine 5-Hydroxytryptophan Aggravates Sepsis-Induced Acute Lung Injury by Promoting Neutrophils Extracellular Traps FormationYumeng Huang0Qian Ji1Yanyan Zhu2Shengqiao Fu3Shuangwei Chen4Liangmei Chu5Yongfei Ren6Yue Wang7Xuan Lei8Jia Gu9Ningzheng Tai10Dadong Liu11Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of Radiation Oncology, Institute of Oncology, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of Radiation Oncology, Institute of Oncology, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of General Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of Radiation Oncology, Institute of Oncology, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of General Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of General Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaDepartment of Intensive Care Unit, Affiliated Hospital, Jiangsu University, Zhenjiang, ChinaExcessive 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. Tph1 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 Tph1 knockout (Tph1−/−), mice promote lipopolysaccharide (LPS)-induced NET formation. Exogenous 5-HT intervention increased LPS-induced NET 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 NET formation in the lung of septic mice.https://www.frontiersin.org/articles/10.3389/fcell.2021.777989/fullsepsisacute lung injury (ALI)5-hydroxytryptophan (5-HT)neutrophil extracellular traps (NETs)neutrophilplatelet |
| spellingShingle | Yumeng Huang Qian Ji Yanyan Zhu Shengqiao Fu Shuangwei Chen Liangmei Chu Yongfei Ren Yue Wang Xuan Lei Jia Gu Ningzheng Tai Dadong Liu Activated Platelets Autocrine 5-Hydroxytryptophan Aggravates Sepsis-Induced Acute Lung Injury by Promoting Neutrophils Extracellular Traps Formation Frontiers in Cell and Developmental Biology sepsis acute lung injury (ALI) 5-hydroxytryptophan (5-HT) neutrophil extracellular traps (NETs) neutrophil platelet |
| title | Activated Platelets Autocrine 5-Hydroxytryptophan Aggravates Sepsis-Induced Acute Lung Injury by Promoting Neutrophils Extracellular Traps Formation |
| title_full | Activated Platelets Autocrine 5-Hydroxytryptophan Aggravates Sepsis-Induced Acute Lung Injury by Promoting Neutrophils Extracellular Traps Formation |
| title_fullStr | Activated Platelets Autocrine 5-Hydroxytryptophan Aggravates Sepsis-Induced Acute Lung Injury by Promoting Neutrophils Extracellular Traps Formation |
| title_full_unstemmed | Activated Platelets Autocrine 5-Hydroxytryptophan Aggravates Sepsis-Induced Acute Lung Injury by Promoting Neutrophils Extracellular Traps Formation |
| title_short | Activated Platelets Autocrine 5-Hydroxytryptophan Aggravates Sepsis-Induced Acute Lung Injury by Promoting Neutrophils Extracellular Traps Formation |
| title_sort | activated platelets autocrine 5 hydroxytryptophan aggravates sepsis induced acute lung injury by promoting neutrophils extracellular traps formation |
| topic | sepsis acute lung injury (ALI) 5-hydroxytryptophan (5-HT) neutrophil extracellular traps (NETs) neutrophil platelet |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.777989/full |
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