PECAM-1 and gelatinase B coexist in vascular cuffs of multiple sclerosis lesions.
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| Abstract |
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.
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| Authors | I Nelissen, D Gveric, J M van Noort, M L Cuzner, G Opdenakker |
| Journal | Neuropathology and applied neurobiology (Neuropathol Appl Neurobiol) Vol. 32 Issue 1 Pg. 15-22 (Feb 2006) ISSN: 0305-1846 [Print] England |
| PMID | 16409549 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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