help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Crocker, S. J.
Right arrow Articles by Campbell, I. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Crocker, S. J.
Right arrow Articles by Campbell, I. L.
(American Journal of Pathology. 2006;169:2104-2116.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060626

Persistent Macrophage/Microglial Activation and Myelin Disruption after Experimental Autoimmune Encephalomyelitis in Tissue Inhibitor of Metalloproteinase-1-Deficient Mice

Stephen J. Crocker*, Jason K. Whitmire*, Ricardo F. Frausto*, Parntip Chertboonmuang*, Paul D. Soloway{dagger}, J. Lindsay Whitton* and Iain L. Campbell*{ddagger}

From the Molecular and Integrative Neurosciences Department,* The Scripps Research Institute, La Jolla, California; the Division of Nutritional Sciences,{dagger} College of Agriculture and Life Sciences, Cornell University, Ithaca, New York; and the School of Molecular and Microbial Biosciences,{ddagger} University of Sydney, Sydney, Australia

Increased leukocyte trafficking into the parenchyma during inflammatory responses in the central nervous system (CNS) is facilitated by the extracellular proteolytic activities of matrix metalloproteinases that are regulated, in part, by the endogenous tissue inhibitors of metalloproteinases (TIMPs). In experimental autoimmune encephalomyelitis (EAE), TIMP-1 gene expression is induced in astrocytes surrounding inflammatory lesions in the CNS. The physiological importance of this temporal and spatial relationship is not clear. Herein, we have addressed the functional role of TIMP-1 in a myelin oligodendrocyte glycoprotein (MOG35-55)-induced model of EAE using TIMP-1-deficient (TIMP-1–/–) C57BL/6 mice. Although CD4+ T-cell immune responses to myelin in wild-type (WT) and TIMP-1–/– mice were similar, analysis of CNS tissues from TIMP-1–/– mice after EAE revealed more severe myelin pathology than that of WT mice. This disruption of myelin was associated with both increased lymphocyte infiltration and microglial/macrophage accumulation in the brain parenchyma. These findings suggest that induction of TIMP-1 by astrocytes during EAE in WT mice represents an inherent cytoprotective response that mitigates CNS myelin injury through the regulation of both immune cell infiltration and microglial activation.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
P. De Sarno, R. C. Axtell, C. Raman, K. A. Roth, D. R. Alessi, and R. S. Jope
Lithium Prevents and Ameliorates Experimental Autoimmune Encephalomyelitis
J. Immunol., July 1, 2008; 181(1): 338 - 345.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Milner, S. J. Crocker, S. Hung, X. Wang, R. F. Frausto, and G. J. del Zoppo
Fibronectin- and Vitronectin-Induced Microglial Activation and Matrix Metalloproteinase-9 Expression Is Mediated by Integrins {alpha}5beta1 and {alpha}vbeta5
J. Immunol., June 15, 2007; 178(12): 8158 - 8167.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Society for Investigative Pathology.