Xiao-Fei Shen, Yang Zhao, Ke Cao, Wen-Xian Guan, Xue Li, Qian Zhang, Yong Zhao, Yi-Tao Ding, Jun-Feng Du
Abstract
Sepsis is defined as an uncontrolled host response to infection, and no specific therapy or drugs have been used in clinical trials currently. Discovering new therapeutic targets for sepsis treatment has always been a central problem in the field of sepsis research. Neutrophils stand at the first line in controlling infection and have been identified to be dysregulated with impaired migration and antimicrobial function during sepsis. Based on our previous results on demonstrating wild-type p53-induced phosphatase 1 in controlling neutrophil development, we explored the possible relationship among Wip1, neutrophils, and sepsis in the present study. Wip1-deficient mice exhibited improved outcomes in cecal ligation and puncture (CLP)-induced sepsis model with enhanced bacterial clearance and less multi-organ damage. The protection seen in Wip1 KO mice was mainly due to an increased accumulation of neutrophils in the primary infectious locus mediated by the decreased internalization of CXCR2, as well as by an increased antimicrobial function. Additionally, we also identified a negative correlation between CXCR2 and Wip1 in human neutrophils during sepsis. Pharmacological inhibition of Wip1 with its inhibitor can also prevent the internalization of CXCR2 on human neutrophils treated with lipopolysaccharides in vitro and significantly improve the outcome in CLP-induced sepsis model. Taken together, our results demonstrate that Wip1 can negatively regulate neutrophil migration and antimicrobial immunity during sepsis and inhibition of Wip1 can be a potential therapeutic target for sepsis treatment.
Pharmacology, Toxicology and Pharmaceutical Science
2
11%
Agricultural and Biological Sciences
2
11%
Medicine and Dentistry
2
11%
Other
0
0%
Unknown
3
17%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 September 2017.
All research outputs
#18,124,233
of 26,587,745 outputs
Outputs from Frontiers in immunology
#21,189
of 33,408 outputs
Outputs of similar age
#213,397
of 331,754 outputs
Outputs of similar age from Frontiers in immunology
#330
of 445 outputs
Altmetric has tracked 26,587,745 research outputs across all sources so far. This one is in the 31st percentile – i.e., 31% of other outputs scored the same or lower than it.
So far Altmetric has tracked 33,408 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.7. This one is in the 36th percentile – i.e., 36% of its peers scored the same or lower than it.
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We're also able to compare this research output to 445 others from the same source and published within six weeks on either side of this one. This one is in the 24th percentile – i.e., 24% of its contemporaries scored the same or lower than it.
