HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zozulya, A. L. Articles by Fabry, Z. Search for Related Content PubMed PubMed Citation Articles by Zozulya, A. L. Articles by Fabry, Z.

Dendritic Cell Transmigration through Brain Microvessel Endothelium Is Regulated by MIP-1 Chemokine and Matrix Metalloproteinases¹

Alla L. Zozulya^*, Emily Reinke^*,, Dana C. Baiu^*, Jozsef Karman^2,, Matyas Sandor^* and Zsuzsanna Fabry^3,*

^* Department of Pathology, University of Wisconsin-Madison, Madison, WI 53706; and Neuroscience Training Program and Cellular and Molecular Pathology Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792

Dendritic cells (DCs) accumulate in the CNS during inflammatory diseases, but the exact mechanism regulating their traffic into the CNS remains to be defined. We now report that MIP-1 increases the transmigration of bone marrow-derived, GFP-labeled DCs across brain microvessel endothelial cell monolayers. Furthermore, occludin, an important element of endothelial tight junctions, is reorganized when DCs migrate across brain capillary endothelial cell monolayers without causing significant changes in the barrier integrity as measured by transendothelial electrical resistance. We show that DCs produce matrix metalloproteinases (MMP) -2 and -9 and GM6001, an MMP inhibitor, decreases both baseline and MIP-1-induced DC transmigration. These observations suggest that DC transmigration across brain endothelial cell monolayers is partly MMP dependent. The migrated DCs express higher levels of CD40, CD80, and CD86 costimulatory molecules and induce T cell proliferation, indicating that the transmigration of DCs across brain endothelial cell monolayers contributes to the maintenance of DC Ag-presenting function. The MMP dependence of DC migration across brain endothelial cell monolayers raises the possibility that MMP blockers may decrease the initiation of T cell recruitment and neuroinflammation in the CNS.

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 National Institutes of Health Grant RO1-NS 37570-01A2 (to Z.F.).

² Current address: Department of Neurology, Center for Neurologic Diseases, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115.

³ Address correspondence and reprint requests to Dr. Zsuzsanna Fabry, Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 1300 University Avenue, 6130 MSC, Madison, WI 53706. E-mail address: zfabry{at}wisc.edu

⁴ Abbreviations used in this paper: DC, dendritic cell; BBB, blood-brain barrier; MS, multiple sclerosis; MMP, matrix metalloproteinase; TEER, transendothelial electrical resistance; BCEC, brain capillary endothelial cell; SEM, scanning electron microscopy; ZO-1, zona occludens-1; Tg, transgenic; NGAL, neutrophil gelatinase B-associated lipocalin; CLSM, confocal laser scanning microscopy.

This article has been cited by other articles:

				G. Rotta, G. Matteoli, E. Mazzini, P. Nuciforo, M. P. Colombo, and M. Rescigno Contrasting roles of SPARC-related granuloma in bacterial containment and in the induction of anti-Salmonella typhimurium immunity J. Exp. Med., March 17, 2008; 205(3): 657 - 667. [Abstract] [Full Text] [PDF]

				I. Ifergan, H. Kebir, M. Bernard, K. Wosik, A. Dodelet-Devillers, R. Cayrol, N. Arbour, and A. Prat The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells Brain, March 1, 2008; 131(3): 785 - 799. [Abstract] [Full Text] [PDF]

				J.-H. Yen, T. Khayrullina, and D. Ganea PGE2-induced metalloproteinase-9 is essential for dendritic cell migration Blood, January 1, 2008; 111(1): 260 - 270. [Abstract] [Full Text] [PDF]