Urokinase receptor is necessary for adequate host defense against pneumococcal pneumonia

The Journal of Immunology : Official Journal of the American Association of Immunologists
Anita W RijneveldTom van der Poll

Abstract

Cell recruitment is a multistep process regulated by cytokines, chemokines, and growth factors. Previous work has indicated that the urokinase plasminogen activator receptor (uPAR) may also play a role in this mechanism, presumably by an interaction with the beta(2) integrin CD11b/CD18. Indeed, an essential role of uPAR in neutrophil recruitment during pulmonary infection has been demonstrated for beta(2) integrin-dependent respiratory pathogens. We investigated the role of uPAR and urokinase plasminogen activator (uPA) during pneumonia caused by a beta(2) integrin-independent respiratory pathogen, Streptococcus pneumoniae. uPAR-deficient (uPAR(-/-)), uPA-deficient (uPA(-/-)), and wild-type (Wt) mice were intranasally inoculated with 10(5) CFU S. pneumoniae. uPAR(-/-) mice showed reduced granulocyte accumulation in alveoli and lungs when compared with Wt mice, which was associated with more S. pneumoniae CFU in lungs, enhanced dissemination of the infection, and a reduced survival. In contrast, uPA(-/-) mice showed enhanced host defense, with more neutrophil influx and less pneumococci in the lungs compared with Wt mice. These data suggest that uPAR is necessary for adequate recruitment of neutrophils into the alveoli and lungs...Continue Reading

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Citations

Apr 12, 2003·Critical Care Medicine·Marcel LeviTom van der Poll
Dec 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nathalie BeaufortDominique Pidard
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Feb 10, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·W Joost WiersingaTom van der Poll

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