Urokinase-type plasminogen activator receptor regulates leukocyte recruitment during experimental pneumococcal meningitis |
| |
Authors: | Paul Robert Winkler Frank Bayerlein Irene Popp Bernadette Pfister Hans-Walter Koedel Uwe |
| |
Institution: | Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|