Urokinase‐Type Plasminogen Activator Receptor Regulates Leukocyte Recruitment during Experimental Pneumococcal Meningitis
Department of Neurology, Klinikum Grosshadern, Ludwig‐Maximilians University, Munich, Germany
Tissue‐type plasminogen activator (tPA) and urokinase‐type plasminogen activator (uPA) have been suggested to play an important role in inflammatory diseases. Increased levels of tPA, uPA, uPA receptor (uPAR), and their inhibitor, plasminogen activator inhibitor (PAI)–1, have been found in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. Here, we show that expression of tPA, uPA, uPAR, PAI‐1, and PAI‐2 is up‐regulated during experimental pneumococcal meningitis. In uPAR‐deficient mice, CSF pleocytosis was significantly attenuated 24 h after infection, compared with that in infected wild‐type (wt) mice. Lack of uPAR did not influence blood‐brain barrier permeability, intracranial pressure, expression of chemokines (keratinocyte‐derived cytokine and macrophage inflammatory protein–2), bacterial killing, or clinical outcome. No differences in pathophysiological alterations were observed in tPA‐deficient mice, compared with those in infected wt mice. These results indicate that uPAR participates in the recruitment of leukocytes to the CSF space during pneumoccal meningitis.
Received 4 August 2004; accepted 24 September 2004; electronically published 25 January 2005.
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Online publication date: 15-Jan-2008.
Online publication date: 11-Nov-2006.
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Online publication date: 15-Feb-2006.
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Financial support: Förderprogramm Forschung und Lehre of the Ludwig‐Maximilians University Munich (support to F.W.); Wilhelm Sander‐Stiftung (support to H.W.P.); Deutsche Forschungsgemeinschaft (support to H.W.P.).
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R.P. and F.W. contributed equally to this work.