Fibronectin changes in eosinophilic meningitis with blood-CSF barrier disruption

Exp Parasitol. 2015 Apr-May:151-152:73-9. doi: 10.1016/j.exppara.2015.02.002. Epub 2015 Feb 7.

Abstract

Fibronectin, which is present at relatively low levels in healthy central nervous systems (CNS), shows increased levels in meningitis. In this study, fibronectin processing was correlated with the increased permeability of the blood-cerebrospinal fluid (CSF) barrier as well as with the formation of eosinophil infiltrates in angiostrongyliasis meningitis. The immunohistochemistry results show matrix metalloproteinase-9 (MMP-9) is localized in the choroid plexus epithelium. Coimmunoprecipitation demonstrated fibronectin strongly binds MMP-9. Furthermore, treatment with the MMP-9 inhibitor GM6001 significantly inhibited fibronectin processing, reduced the blood-CSF barrier permeability, and decreased the eosinophil counts. The decreased fibronectin processing in CSF implies decreased cellular invasion of the subarachnoid space across the blood-CSF barrier. Therefore, increased fibronectin processing may be associated with barrier disruption and participate in the extravasation and migration of eosinophils into the CNS during experimental parasitic infection.

Keywords: Angiostrongylus cantonensis; Evans blue; Fibronectin; Meningitis.

MeSH terms

  • Angiostrongylus cantonensis*
  • Animals
  • Antibodies, Monoclonal
  • Blotting, Western
  • Choroid Plexus / enzymology
  • Dipeptides / pharmacology
  • Eosinophilia / blood
  • Eosinophilia / cerebrospinal fluid
  • Eosinophilia / metabolism*
  • Eosinophilia / parasitology
  • Fibronectins / cerebrospinal fluid
  • Fibronectins / immunology
  • Fibronectins / metabolism*
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Meningitis / blood
  • Meningitis / cerebrospinal fluid
  • Meningitis / metabolism*
  • Meningitis / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Permeability
  • Random Allocation
  • Rats
  • Snails
  • Specific Pathogen-Free Organisms
  • Strongylida Infections / blood
  • Strongylida Infections / cerebrospinal fluid
  • Strongylida Infections / metabolism*

Substances

  • Antibodies, Monoclonal
  • Dipeptides
  • Fibronectins
  • Matrix Metalloproteinase Inhibitors
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Matrix Metalloproteinase 9