| First Author | Tseng A | Year | 2018 |
| Journal | Front Med (Lausanne) | Volume | 5 |
| Pages | 134 | PubMed ID | 29780806 |
| Mgi Jnum | J:309627 | Mgi Id | MGI:6758851 |
| Doi | 10.3389/fmed.2018.00134 | Citation | Tseng A, et al. (2018) Myeloperoxidase Negatively Regulates Neutrophil-Endothelial Cell Interactions by Impairing alphaMbeta2 Integrin Function in Sterile Inflammation. Front Med (Lausanne) 5:134 |
| abstractText | 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 alphaMbeta2 integrin during sterile inflammation. In this study, we further demonstrate a crucial role for myeloperoxidase (MPO) in regulating the adhesive function of neutrophils through alphaMbeta2 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 alphaMbeta2 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 alphaMbeta2 integrin function under sterile inflammatory conditions. |
