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 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.
Nelissen
I
I
Laboratory of Immunobiology, Rega Institute for Medical Research, Catholic University of Leuven, Leuven, Belgium.
Gveric
D
D
van Noort
J M
JM
Cuzner
M L
ML
Opdenakker
G
G
D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9