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

TitleDifferential attenuation of β2 integrin-dependent and -independent neutrophil migration by Ly6G ligation.
Publication TypeJournal Article
Year of Publication2019
AuthorsCunin, P, Lee, PY, Kim, E, Schmider, AB, Cloutier, N, Paré, A, Gunzer, M, Soberman, RJ, Lacroix, S, Boilard, E, Lefort, CT, Nigrovic, PA
JournalBlood Adv
Volume3
Issue3
Pagination256-267
Date Published2019 Feb 12
ISSN2473-9537
Abstract

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 β2 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 β2 integrins varied with stimulus, proving dispensable for neutrophil entry in 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 β2 integrin dependence in neutrophil migration.

DOI10.1182/bloodadvances.2018026732
Alternate JournalBlood Adv
PubMed ID30696624
PubMed Central IDPMC6373735
Grant ListP30 AR070253 / AR / NIAMS NIH HHS / United States
R01 AR065538 / AR / NIAMS NIH HHS / United States
R35 GM124911 / GM / NIGMS NIH HHS / United States
T32 AI007512 / AI / NIAID NIH HHS / United States