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Here we have tested the hypothesis that this effect of <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> is mediated by effects on migration of innate immune cells to the site of infection. Using the air pouch as a model of endodontic infection in mice, we showed that neutrophil accumulation at the site of infection with a mixture of endodontic pathogens is significantly reduced in <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content>\u2010deficient mice. Reduced neutrophil accumulation in the absence of <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> was accompanied by an increase in bacterial load. <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content>\u2010deficiency did not affect neutrophil survival, <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>2 ligand expression, or the production of inflammatory cytokines in the air pouch. <jats:italic>In vitro<\/jats:italic>,<jats:styled-content style=\"fixed-case\"> OPN<\/jats:styled-content> enhanced neutrophil migration to <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>1, whereas i<jats:italic>n vivo<\/jats:italic>, inhibition of <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>2 suppressed cellular infiltration in air pouches of infected wild\u2010type mice by &gt; 50%, but had no effect in <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content>\u2010deficient mice. <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> increased cell surface expression of <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>2 on bone marrow neutrophils in an integrin\u2010<jats:italic>\u03b1<\/jats:italic><jats:sub>v<\/jats:sub>\u2010dependent manner, and suppressed the internalization of <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>2 in the absence of ligand. Together, these results support a model where the protective effect of <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content> results from enhanced initial neutrophil accumulation at sites of infection resulting in optimal bacterial killing. We describe a novel mechanism for this effect of <jats:styled-content style=\"fixed-case\">OPN<\/jats:styled-content>: integrin\u2010<jats:italic>\u03b1<\/jats:italic><jats:sub>v<\/jats:sub>\u2010dependent suppression of <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>2 internalization in neutrophils, which increases the ability of these cells to migrate to sites of infection in response to <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>2 ligands.<\/jats:p>","DOI":"10.1111\/imm.12668","type":"journal-article","created":{"date-parts":[[2016,9,6]],"date-time":"2016-09-06T14:03:53Z","timestamp":1473170633000},"page":"74-86","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Modulation of infection\u2010mediated migration of neutrophils and <scp>CXCR<\/scp>2 trafficking by 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