| First Author | Hao L | Year | 2019 |
| Journal | J Leukoc Biol | Volume | 106 |
| Issue | 5 | Pages | 1117-1127 |
| PubMed ID | 31216371 | Mgi Jnum | J:280464 |
| Mgi Id | MGI:6368309 | Doi | 10.1002/JLB.3A0518-184RR |
| Citation | Hao L, et al. (2019) Critical role for PI3Kgamma-dependent neutrophil reactive oxygen species in WKYMVm-induced microvascular hyperpermeability. J Leukoc Biol 106(5):1117-1127 |
| abstractText | PI3K has been indicated in regulating microvascular permeability changes during inflammation. However, its role in neutrophil-driven microvascular leakage in acute inflammation remains unclear. Using intravital microscopy in mice, we examined the role of PI3Kgamma and PI3Kdelta in formyl peptide WKYMVm- and chemokine CXCL2-induced permeability changes and assessed simultaneously neutrophil adhesion and emigration in post-capillary venules of murine cremaster muscle. We found a PI3Kgamma-specific mechanism in WKYMVm-induced but not CXCL2-induced microvascular hyperpermeability. The increased microvascular permeability triggered by WKYMVm was not entirely due to neutrophil adhesion and emigration in cremasteric microvasculature in different PI3K transgenic mouse strains. The PI3Kgamma-specific hyperpermeability was neutrophil-mediated as this was reduced after depletion of neutrophils in mouse circulation. Chimeric mice with PI3Kgamma-deficient neutrophils but wild-type endothelium also showed reduced hyperpermeability. Furthermore, we found that the catalytic function of PI3Kgamma was required for reactive oxygen species (ROS) generation in neutrophils stimulated with WKYMVm. Pharmacological scavenging PI3Kgamma-dependent ROS in the tissue eliminated the discrepancy in hyperpermeability between different PI3K transgenic mice and alleviated WKYMVm-induced microvascular leakage in all mouse strains tested. In conclusion, our study uncovers the critical role for PI3Kgamma-dependent ROS generation by neutrophils in formyl peptide-induced microvascular hyperpermeability during neutrophil recruitment. |
