Urokinase-type plasminogen activator receptor regulates leukocyte recruitment during experimental pneumococcal meningitis.
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.
Paul
Robert
R
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany.
Winkler
Frank
F
Bayerlein
Irene
I
Popp
Bernadette
B
Pfister
Hans-Walter
HW
Koedel
Uwe
U
D000818:Animals; D002465:Cell Movement; D007962:Leukocytes / Q000502:physiology*; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000276:immunology / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000502:physiology
C524899:Plaur protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator