| First Author | Wang JX | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 7 | Pages | 1489-98 |
| PubMed ID | 22661700 | Mgi Jnum | J:189105 |
| Mgi Id | MGI:5444350 | Doi | 10.1182/blood-2012-01-404046 |
| Citation | Wang JX, et al. (2012) Ly6G ligation blocks recruitment of neutrophils via a beta2-integrin-dependent mechanism. Blood 120(7):1489-98 |
| abstractText | Ly6G is a glycosylphosphatidylinositol (GPI)-anchored protein of unknown function that is commonly targeted to induce experimental neutrophil depletion in mice. In the present study, we found that doses of anti-Ly6G Abs too low to produce sustained neutropenia remained capable of inhibiting experimental arthritis, leaving joint tissues free of infiltrating neutrophils. Thioglycollate-stimulated peritonitis was also attenuated. No alteration in neutrophil apoptosis was observed, implicating impaired recruitment. Indeed, Ly6G ligation abrogated neutrophil migration toward LTB(4) and other chemoattractants in a transwell system. Exploring the basis for this blockade, we identified colocalization of Ly6G and beta2-integrins by confocal microscopy and confirmed close association by both coimmunoprecipitation and fluorescence lifetime imaging microscopy. Anti-Ly6G Ab impaired surface expression of beta2-integrins in LTB(4)-stimulated neutrophils and mimicked CD11a blockade in inhibiting both ICAM-1 binding and firm adhesion to activated endothelium under flow conditions. Correspondingly, migration of beta2-integrin-deficient neutrophils was no longer inhibited by anti-Ly6G. These results demonstrate that experimental targeting of Ly6G has functional effects on the neutrophil population and identify a previously unappreciated role for Ly6G as a modulator of neutrophil migration to sites of inflammation via a beta2-integrin-dependent mechanism. |
