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Urokinase receptor is necessary for bacterial defense against pneumonia-derived septic melioidosis by facilitating phagocytosis.
J Immunol. 2010 Mar 15; 184(6):3079-86.JI

Abstract

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.

Authors+Show Affiliations

Center for Infection and Immunity Amsterdam, University of Amsterdam, Amsterdam, The Netherlands. w.j.wiersinga@amc.uva.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20142364

Citation

Wiersinga, W Joost, et al. "Urokinase Receptor Is Necessary for Bacterial Defense Against Pneumonia-derived Septic Melioidosis By Facilitating Phagocytosis." Journal of Immunology (Baltimore, Md. : 1950), vol. 184, no. 6, 2010, pp. 3079-86.
Wiersinga WJ, Kager LM, Hovius JW, et al. Urokinase receptor is necessary for bacterial defense against pneumonia-derived septic melioidosis by facilitating phagocytosis. J Immunol. 2010;184(6):3079-86.
Wiersinga, W. J., Kager, L. M., Hovius, J. W., van der Windt, G. J., de Vos, A. F., Meijers, J. C., Roelofs, J. J., Dondorp, A., Levi, M., Day, N. P., Peacock, S. J., & van der Poll, T. (2010). Urokinase receptor is necessary for bacterial defense against pneumonia-derived septic melioidosis by facilitating phagocytosis. Journal of Immunology (Baltimore, Md. : 1950), 184(6), 3079-86. https://doi.org/10.4049/jimmunol.0901008
Wiersinga WJ, et al. Urokinase Receptor Is Necessary for Bacterial Defense Against Pneumonia-derived Septic Melioidosis By Facilitating Phagocytosis. J Immunol. 2010 Mar 15;184(6):3079-86. PubMed PMID: 20142364.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Urokinase receptor is necessary for bacterial defense against pneumonia-derived septic melioidosis by facilitating phagocytosis. AU - Wiersinga,W Joost, AU - Kager,Liesbeth M, AU - Hovius,Joppe W R, AU - van der Windt,Gerritje J W, AU - de Vos,Alex F, AU - Meijers,Joost C M, AU - Roelofs,Joris J, AU - Dondorp,Arjen, AU - Levi,Marcel, AU - Day,Nicholas P, AU - Peacock,Sharon J, AU - van der Poll,Tom, Y1 - 2010/02/08/ PY - 2010/2/10/entrez PY - 2010/2/10/pubmed PY - 2010/5/4/medline SP - 3079 EP - 86 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 184 IS - 6 N2 - 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/20142364/Urokinase_receptor_is_necessary_for_bacterial_defense_against_pneumonia_derived_septic_melioidosis_by_facilitating_phagocytosis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=20142364 DB - PRIME DP - Unbound Medicine ER -