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,
Departments of
*
Experimental Internal Medicine,
Internal Medicine,
Pathology, and
Infectious Diseases, Tropical Medicine, and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and
¶ Center for Transgene Technology and Gene Therapy, Flemish Interuniversity Institute for Biotechnology, Leuven, Belgium
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 
2
integrin CD11b/CD18. Indeed, an essential role of uPAR in neutrophil
recruitment during pulmonary infection has been demonstrated for
2 integrin-dependent respiratory pathogens. We
investigated the role of uPAR and urokinase plasminogen activator (uPA)
during pneumonia caused by a 2 integrin-independent
respiratory pathogen, Streptococcus pneumoniae.
uPAR-deficient (uPAR-/-), uPA-deficient
(uPA-/-), and wild-type (Wt) mice were intranasally
inoculated with 105 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 during pneumonia
caused by S. pneumoniae, a pathogen eliciting a
2 integrin-independent inflammatory response. This
function is even more pronounced when uPAR is unoccupied by
uPA.
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