Interactions of neutrophils with endothelial cells (ECs) and platelets contribute to tissue damage and vascular occlusion under sterile inflammatory conditions. However, the molecular mechanisms regulating the cell-cell interactions remain poorly understood. Previous studies suggest that reactive oxygen species, such as hydrogen peroxide (H2O2), produced from NADPH oxidase 2 play a critical role in platelet-neutrophil interactions by regulating the function of neutrophil αMβ2 integrin during sterile inflammation. In this study, we further demonstrate a crucial role for myeloperoxidase (MPO) in regulating the adhesive function of neutrophils through αMβ2 integrin. Using real-time fluorescence intravital microscopy and in vitro assays, we showed that loss of MPO promoted neutrophil-EC interactions and neutrophil emigration but did not affect neutrophil-platelet interactions under inflammatory conditions. Using genetic and pharmacologic approaches, we found that following agonist stimulation, MPO knockout (KO) neutrophils exhibited a significant increase in extracellular H2O2 and surface level of αMβ2 integrin and that these effects were dependent on MPO activity. Our in vivo studies using an ischemia/reperfusion-induced hepatic inflammation model revealed that compared to wild-type mice, neutrophils from MPO KO mice-displayed a pro-migratory phenotype while ameliorating tissue damage. These results suggest that MPO plays a negative role in the adhesive and migratory function of neutrophils by impairing αMβ2 integrin function under sterile inflammatory conditions.
Pharmacology, Toxicology and Pharmaceutical Science
4
7%
Immunology and Microbiology
4
7%
Other
11
18%
Unknown
18
30%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 04 May 2018.
All research outputs
#18,606,163
of 23,047,237 outputs
Outputs from Frontiers in Medicine
#4,027
of 5,809 outputs
Outputs of similar age
#253,318
of 326,669 outputs
Outputs of similar age from Frontiers in Medicine
#88
of 104 outputs
Altmetric has tracked 23,047,237 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,809 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.3. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
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We're also able to compare this research output to 104 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
