PECAM-1 and gelatinase B coexist in vascular cuffs of multiple sclerosis lesions

In multiple sclerosis (MS), the matrix metalloprotease (MMP) gelatinase B/MMP‐9 and platelet endothelial cell adhesion molecule (PECAM)‐1 have both been implicated in trans‐endothelial infiltration of leucocytes into the brain, but their functional connection has not yet been investigated. We invest...

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Bibliographic Details
Published in:Neuropathology and applied neurobiology Vol. 32; no. 1; pp. 15 - 22
Main Authors: Nelissen, I., Gveric, D., Van Noort, J. M., Cuzner, M. L., Opdenakker, G.
Format: Journal Article
Language:English
Published: Oxford, UK Blackwell Publishing Ltd 01.02.2006
Blackwell Science
Subjects:
Biological and medical sciences
Blotting, Western
Brain - blood supply
Brain - metabolism
Brain - pathology
Cell Movement - physiology
Cells, Cultured
Endothelial Cells - metabolism
Flow Cytometry
Human viral diseases
Humans
Immunohistochemistry
Infectious diseases
Leukocytes, Mononuclear - metabolism
Malformations of the nervous system
Matrix Metalloproteinase 9 - metabolism
Medical sciences
MMP-7
MMP-9
multiple sclerosis
Multiple Sclerosis - metabolism
Multiple Sclerosis - pathology
Neurology
PECAM-1
Platelet Endothelial Cell Adhesion Molecule-1 - metabolism
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
Immunohistochemistry
PECAM-1
Multiple sclerosis
Nervous system diseases
Enzyme
Metalloendopeptidases
Gelatinase B
Inflammatory disease
Peptidases
Cuff
Central nervous system disease
Hydrolases
Lesion
MMP-7
MMP-9
ISSN:0305-1846, 1365-2990
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Summary:In multiple sclerosis (MS), the matrix metalloprotease (MMP) gelatinase B/MMP‐9 and platelet endothelial cell adhesion molecule (PECAM)‐1 have both been implicated in trans‐endothelial infiltration of leucocytes into the brain, but their functional connection has not yet been investigated. We investigated the expression of gelatinase B and PECAM‐1 in  post mortem brains of MS patients by immunohistochemistry. Because increased soluble PECAM‐1 serum levels have been observed in MS patients, we also tested in vitro whether this could be due to cleavage of PECAM‐1 by gelatinase B or matrilysin‐1/MMP‐7. Constitutive expression of PECAM‐1 was found on brain endothelial cells, whilst in active MS lesions cell‐bound PECAM‐1 was highly up‐regulated on foamy macrophages in perivascular infiltrates and co‐localized with gelatinase B. However, human THP‐1 monocyte‐bound or soluble recombinant PECAM‐1 were both resistant to proteolytic cleavage by gelatinase B or matrilysin‐1 in vitro, as demonstrated by Western blot analysis and flow cytometry. These results suggest that PECAM‐1 and gelatinase B may complement each other during the transmigration of the blood–brain barrier by mononuclear cells.
Bibliography:ark:/67375/WNG-92T3P7PH-4
ArticleID:NAN677
istex:367B03968CA39280E4D0A412873B52C446A085F1
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0305-1846
1365-2990
DOI:10.1111/j.1365-2990.2006.00677.x