Ultrastructural localization of matrix metalloproteinase-9 in eosinophils from the cerebrospinal fluid of mice with eosinophilic meningitis caused by Angiostrongylus cantonensis

Abstract

Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of eosinophilic meningitis caused by Angiostrongylus cantonensis. In the present study, such meningitis in mice was found to be associated with elevated expression of MMP-9 mRNA, elevated MMP-9 concentrations and enhanced MMP-9 activity in the cerebrospinal fluid (CSF). Immunocytochemistry showed that an anti-MMP-9 antibody reacted with macrophages, neutrophils and eosinophils from the CSF. As eosinophils are generally considered to be effector cells in host defence against A. cantonensis infection, high-resolution immuno-electron microscopy was then used to confirm the localization of MMP-9 in the eosinophils from the CSF. The method used, which was based on immunogold, indicated that the eosinophilic MMP-9 was mostly localized in the 'small' granules in the cytoplasm and along the cell membrane, and not in the crystalloid-containing secretory granules observed. It therefore appears that MMP-9 is synthesised and/or stored in the small granules of the eosinophils, and is released into the subarachnoid space of the host's brain by secretion or cell rupture.