Urokinase receptor (urokinase-type plasminogen activator receptor [uPAR], CD87), 
a GPI-anchored protein, is considered to play an important role in inflammation 
and fibrinolysis. The Gram-negative bacterium Burkholderia pseudomallei is able 
to survive and replicate within leukocytes and causes melioidosis, an important 
cause of pneumonia-derived community-acquired sepsis in Southeast Asia. In this 
study, we investigated the expression and function of uPAR both in patients with 
septic melioidosis and in a murine model of experimental melioidosis. uPAR mRNA 
and surface expression was increased in patients with septic melioidosis in/on 
both peripheral blood monocytes and granulocytes as well as in the pulmonary 
compartment during experimental pneumonia-derived melioidosis in mice. 
uPAR-deficient mice intranasally infected with B. pseudomallei showed an 
enhanced growth and dissemination of B. pseudomallei when compared with 
wild-type mice, corresponding with increased pulmonary and hepatic inflammation. 
uPAR knockout mice demonstrated significantly reduced neutrophil migration 
toward the pulmonary compartment after inoculation with B. pseudomallei. Further 
in vitro experiments showed that uPAR-deficient macrophages and granulocytes 
display a markedly impaired phagocytosis of B. pseudomallei. Additional studies 
showed that uPAR deficiency did not influence hemostatic and fibrinolytic 
responses during severe melioidosis. These data suggest that uPAR is crucially 
involved in the host defense against sepsis caused by B. pseudomallei by 
facilitating the migration of neutrophils toward the primary site of infection 
and subsequently facilitating the phagocytosis of B. pseudomallei.