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* Theodor Kocher Institute, University of Bern, Bern, Switzerland; and
Max Planck Institute for Molecular Biomedicine, Münster, Germany
In multiple sclerosis and in its animal model experimental autoimmune encephalomyelitis (EAE), inflammatory cells migrate across the endothelial blood-brain barrier (BBB) and gain access to the CNS. It is well-established that 
4 integrins are actively involved in leukocyte recruitment across the BBB during EAE. In contrast, the role of endothelial E- and P-selectin in this process has been a controversial issue. In this study, we demonstrate that P-selectin protein can be detected in meningeal blood vessel endothelial cells in healthy SJL and C57BL/6 mice and on rare parenchymal CNS blood vessels in C57BL/6, but not SJL, mice. During EAE, expression of P-selectin but not E-selectin was found up-regulated on inflamed CNS microvessels surrounded by inflammatory infiltrates irrespective of their meningeal or parenchymal localization with a more prominent immunostaining detected in C57BL/6 as compared with SJL mice. P-selectin immunostaining could be localized to CNS endothelial cells and to CD41-positive platelets adhering to the vessel wall. Despite the presence of P-selectin in wild-type mice, E/P-selectin-deficient SJL and C57BL/6 mice developed clinical EAE indistinguishable from wild-type mice. Absence of E- and P-selectin did neither influence the activation of myelin-specific T cells nor the composition of the cellular infiltrates in the CNS during EAE. Finally, endothelial-specific tetracycline-inducible expression of E-selectin at the BBB in transgenic C57BL/6 mice did not alter the development of EAE. Thus, E- and P-selectin are not required for leukocyte recruitment across the BBB and the development of EAE in C57BL/6 and in SJL mice.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a grant of the Swiss National Foundation (3100A0_118390) to B.E.
2 Address correspondence and reprint requests to Dr. Britta Engelhardt, Theodor Kocher Institute, University of Bern, Freiestrasse 1, CH-3012 Bern, Switzerland. E-mail address: bengel{at}tki.unibe.ch
3 Abbreviations used in this paper: MS, multiple sclerosis; EAE, experimental autoimmune encephalomyelitis; BBB, blood-brain barrier; PLP, proteolipid protein; MOG, myelin oligodendrocyte glycoprotein; PSGL, P-selectin glycoprotein ligand; p.i., postimmunization; TET, tetracycline; vWF, von Willebrand factor.
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  B. Petri, M. Phillipson, and P. Kubes The Physiology of Leukocyte Recruitment: An In Vivo Perspective J. Immunol., May 15, 2008; 180(10): 6439 - 6446. [Abstract] [Full Text] [PDF]
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