| First Author | Kuwano Y | Year | 2016 |
| Journal | J Immunol | Volume | 196 |
| Issue | 9 | Pages | 3828-33 |
| PubMed ID | 26976957 | Mgi Jnum | J:310510 |
| Mgi Id | MGI:6760278 | Doi | 10.4049/jimmunol.1500532 |
| Citation | Kuwano Y, et al. (2016) Galphai2 and Galphai3 Differentially Regulate Arrest from Flow and Chemotaxis in Mouse Neutrophils. J Immunol 196(9):3828-33 |
| abstractText | Leukocyte recruitment to inflammation sites progresses in a multistep cascade. Chemokines regulate multiple steps of the cascade, including arrest, transmigration, and chemotaxis. The most important chemokine receptor in mouse neutrophils is CXCR2, which couples through Galphai2- and Galphai3-containing heterotrimeric G proteins. Neutrophils arrest in response to CXCR2 stimulation. This is defective in Galphai2-deficient neutrophils. In this study, we show that Galphai3-deficient neutrophils showed reduced transmigration but normal arrest in mice. We also tested Galphai2- or Galphai3-deficient neutrophils in a CXCL1 gradient generated by a microfluidic device. Galphai3-, but not Galphai2-, deficient neutrophils showed significantly reduced migration and directionality. This was confirmed in a model of sterile inflammation in vivo. Galphai2-, but not Galphai3-, deficient neutrophils showed decreased Ca(2+) flux in response to CXCR2 stimulation. Conversely, Galphai3-, but not Galphai2-, deficient neutrophils exhibited reduced AKT phosphorylation upon CXCR2 stimulation. We conclude that Galphai2 controls arrest and Galphai3 controls transmigration and chemotaxis in response to chemokine stimulation of neutrophils. |
