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Publication : Differential attenuation of β2 integrin-dependent and -independent neutrophil migration by Ly6G ligation.

First Author  Cunin P Year  2019
Journal  Blood Adv Volume  3
Issue  3 Pages  256-267
PubMed ID  30696624 Mgi Jnum  J:298272
Mgi Id  MGI:6458234 Doi  10.1182/bloodadvances.2018026732
Citation  Cunin P, et al. (2019) Differential attenuation of beta2 integrin-dependent and -independent neutrophil migration by Ly6G ligation. Blood Adv 3(3):256-267
abstractText  Antibody ligation of the murine neutrophil surface protein Ly6G disrupts neutrophil migration in some contexts but not others. We tested whether this variability reflected divergent dependence of neutrophil migration on beta2 integrins, adhesion molecules that interact with Ly6G at the neutrophil surface. In integrin-dependent murine arthritis, Ly6G ligation attenuated joint inflammation, even though mice lacking Ly6G altogether developed arthritis normally. By contrast, Ly6G ligation had no impact on integrin-independent neutrophil migration into inflamed lung. In peritoneum, the role of beta2 integrins varied with stimulus, proving dispensable for neutrophil entry in Escherichia coli peritonitis but contributory in interleukin 1 (IL-1)-mediated sterile peritonitis. Correspondingly, Ly6G ligation attenuated only IL-1 peritonitis, disrupting the molecular association between integrins and Ly6G and inducing cell-intrinsic blockade restricted to integrin-dependent migration. Consistent with this observation, Ly6G ligation impaired integrin-mediated postadhesion strengthening for neutrophils arresting on activated cremaster endothelium in vivo. Together, these findings identify selective inhibition of integrin-mediated neutrophil emigration through Ly6G ligation, highlighting the marked site and stimulus specificity of beta2 integrin dependence in neutrophil migration.
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