Premium
Modulation of infection‐mediated migration of neutrophils and CXCR 2 trafficking by osteopontin
Author(s) -
Singh Rani,
Hui Tommy,
Matsui Aritsune,
Allahem Ziyad,
Johnston Christopher D.,
RuizTorruella Montserrat,
Rittling Susan R.
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12668
Subject(s) - osteopontin , internalization , cxc chemokine receptors , cxcl1 , immunology , inflammation , innate immune system , chemokine , biology , integrin , microbiology and biotechnology , receptor , chemistry , immune system , chemokine receptor , biochemistry
Summary Osteopontin ( OPN ) is a pro‐inflammatory protein that paradoxically protects against inflammation and bone destruction in a mouse model of endodontic infection. Here we have tested the hypothesis that this effect of OPN 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 OPN ‐deficient mice. Reduced neutrophil accumulation in the absence of OPN was accompanied by an increase in bacterial load. OPN ‐deficiency did not affect neutrophil survival, CXCR 2 ligand expression, or the production of inflammatory cytokines in the air pouch. In vitro , OPN enhanced neutrophil migration to CXCL 1, whereas i n vivo , inhibition of CXCR 2 suppressed cellular infiltration in air pouches of infected wild‐type mice by > 50%, but had no effect in OPN ‐deficient mice. OPN increased cell surface expression of CXCR 2 on bone marrow neutrophils in an integrin‐ α v ‐dependent manner, and suppressed the internalization of CXCR 2 in the absence of ligand. Together, these results support a model where the protective effect of OPN results from enhanced initial neutrophil accumulation at sites of infection resulting in optimal bacterial killing. We describe a novel mechanism for this effect of OPN : integrin‐ α v ‐dependent suppression of CXCR 2 internalization in neutrophils, which increases the ability of these cells to migrate to sites of infection in response to CXCR 2 ligands.