NR AWQA
AU Viegas,P.; Chaverot,N.; Perriere,N.; Enslen,H.; Couraud,P.O.; Cazaubon,S.
TI Junctional expression of the prion protein PrPc by brain endothelial cells: a role in trans-endothelial migration of U937 human monocytic cells
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions CE-52
PT Konferenz-Poster
AB Conversion of prion protein (PrPc ) to its protease-resistant isoform is involved in the pathogenesis of prion diseases. Although PrPc is highly expressed in neurons and other cell types, its physiological function still remains elusive. Here we intended to evaluate its expression, subcellular localization and putative function in brain endothelial cells, which constitute the blood-brain barrier. We detected its preferred expression at intercellular junctions of freshly isolated brain microvessels and cultured brain endothelial cells of mouse, rat and human origin, co-localized with the adhesion molecule platelet endothelial cell adhesion molecule-1 (PECAM-1); moreover, both PrPc and PECAM-1 were present in raft membrane microdomains. Using mixed cultures of wild type and PrPc -deficient mouse brain endothelial cells, we observed that PrPc accumulation at cell-cell contacts was likely dependent on homophilic interactions between adjacent cells. Moreover, we report that anti-PrPc antibodies unexpectedly inhibited transmigration of U937 human monocytic cells through brain endothelial cells, while not affecting cell adhesion. A similar inhibitory effect was observed with four anti-PrPc antibodies and blocking anti-PECAM-1 antibodies as control. Our results strongly support the conclusion that PrPc is expressed by brain endothelium as a junctional protein which is involved in the trans-endothelial migration of monocytic cells.
AD P. Viegas, N. Chaverot, N. Perrière, P.-O. Couraud, S. Cazaubon: Institut Cochin, Département de Biologie Cellulaire, Paris, F-75014 France, INSERM, U567, Paris, F-75014 France; CNRS, UMR 8104, Paris, F-75014 France, Université Paris Descartes, Faculté de Médecine René Descartes, UMR-S 8104, Paris, F-75014 France; H. Enslen: INSERM, U536, Paris, F-75005 France; Université Pierre et Marie Curie (UPMC-Paris 6), Paris, F-75005 France. Institut du Fer à Moulin, Paris, F-75005 France. E-mail: cazaubon@cochin.inserm.fr
SP englisch
PO Italien