Format

Send to

Choose Destination
BMC Neurosci. 2009 Mar 6;10:17. doi: 10.1186/1471-2202-10-17.

Matrix metalloproteinase-7 facilitates immune access to the CNS in experimental autoimmune encephalomyelitis.

Author information

1
Division of Biomedical Sciences, University of California Riverside, 900 University Avenue, Riverside, CA 92521-0121, USA. lmccandles@rusd.k12.ca.us

Abstract

BACKGROUND:

Metalloproteinase inhibitors can protect mice against experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Matrix metalloproteinase-9 (MMP-9) has been implicated, but it is not clear if other MMPs are also involved, including matrilysin/MMP-7 - an enzyme capable of cleaving proteins that are essential for blood brain barrier integrity and immune suppression.

RESULTS:

Here we report that MMP-7-deficient (mmp7-/-) mice on the C57Bl/6 background are resistant to EAE induced by myelin oligodendrocyte glycoprotein (MOG). Brain sections from MOG-primed mmp7-/-mice did not show signs of immune cell infiltration of the CNS, but MOG-primed wild-type mice showed extensive vascular cuffing and mononuclear cell infiltration 15 days after vaccination. At the peak of EAE wild-type mice had MMP-7 immuno-reactive cells in vascular cuffs that also expressed the macrophage markers Iba-1 and Gr-1, as well as tomato lectin. MOG-specific proliferation of splenocytes, lymphocytes, CD4+ and CD8+ cells were reduced in cells isolated from MOG-primed mmp7-/- mice, compared with MOG-primed wild-type mice. However, the adoptive transfer of splenocytes and lymphocytes from MOG-primed mmp7-/- mice induced EAE in naïve wild-type recipients, but not naïve mmp7-/- recipients. Finally, we found that recombinant MMP-7 increased permeability between endothelial cells in an in vitro blood-brain barrier model.

CONCLUSION:

Our findings suggest that MMP-7 may facilitate immune cell access or re-stimulation in perivascular areas, which are critical events in EAE and multiple sclerosis, and provide a new therapeutic target to treat this disorder.

PMID:
19267908
PMCID:
PMC2660336
DOI:
10.1186/1471-2202-10-17
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center