Efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS
Author
Zhang, Pu-HongZhang, Wen-Wu
Wang, Shun-Shun
Wu, Cheng-Hua
Ding, Yang-Dong
Wu, Xin-Yi
Smith, Fang Gao
Hao, Yu
Jin, Sheng-Wei
Publication date
2024-01-09
Metadata
Show full item recordAbstract
The lymphatic vasculature is the natural pathway for the resolution of inflammation, yet the role of pulmonary lymphatic drainage function in sepsis-induced acute respiratory distress syndrome (ARDS) remains poorly characterized. In this study, indocyanine green-near infrared lymphatic living imaging was performed to examine pulmonary lymphatic drainage function in septic mouse models. We found that the pulmonary lymphatic drainage was impaired owing to the damaged lymphatic structure in sepsis-induced ARDS. Moreover, prior lymphatic defects by blocking vascular endothelial growth factor receptor-3 (VEGFR-3) worsened sepsis-induced lymphatic dysfunction and inflammation. Posttreatment with vascular endothelial growth factor-C (Cys156Ser) (VEGF-C156S), a ligand of VEGFR-3, ameliorated lymphatic drainage by rejuvenating lymphatics to reduce the pulmonary edema and promote draining of pulmonary macrophages and neutrophils to pretracheal lymph nodes. Meanwhile, VEGF-C156S posttreatment reversed sepsis-inhibited CC chemokine ligand 21 (CCL21), which colocalizes with pulmonary lymphatic vessels. Furthermore, the advantages of VEGF-C156S on the drainage of inflammatory cells and edema fluid were abolished by blocking VEGFR-3 or CCL21. These results suggest that efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS. Our findings offer a therapeutic approach to sepsis-induced ARDS by promoting lymphatic drainage function.Citation
Zhang PH, Zhang WW, Wang SS, Wu CH, Ding YD, Wu XY, Smith FG, Hao Y, Jin SW. Efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS. JCI Insight. 2024 Jan 9;9(1):e173440. doi: 10.1172/jci.insight.173440Type
ArticleAdditional Links
https://insight.jci.org/articles/view/173440PMID
37971881Journal
JCI insightae974a485f413a2113503eed53cd6c53
10.1172/jci.insight.173440