ACTIVATION OF ASTROCYTES IN THE SPINAL-CORD OF MICE CHRONICALLY INFECTED WITH A NEUROTROPIC CORONAVIRUS

被引:111
作者
SUN, N
GRZYBICKI, D
CASTRO, RF
MURPHY, S
PERLMAN, S
机构
[1] UNIV IOWA,DEPT PEDIAT,MED LABS 207,IOWA CITY,IA 52242
[2] UNIV IOWA,DEPT PATHOL,IOWA CITY,IA 52242
[3] UNIV IOWA,DEPT MICROBIOL,IOWA CITY,IA 52242
[4] UNIV IOWA,DEPT PHARMACOL,IOWA CITY,IA 52242
关键词
D O I
10.1006/viro.1995.0021
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV-JHM) develop a demyelinating encephalomyelitis several weeks after infection. Astrogliosis and infiltration of inflammatory cells are prominent findings in the brains and spinal cords of infected mice. In this report, astrocytes in infected spinal cords were analyzed for expression of three pleiotropic cytokines, TNF-alpha, IL-1 beta, and IL-6; Type 2 nitric oxide synthase (iNOS); and MHC class I and II antigen. The data show that all three cytokines and iNOS are expressed by astrocytes in chronically infected spinal cords. These activated astrocytes are localized to areas of virus infection and demyelination, although most of the astrocytes expressing these proteins are not MHV-infected. MHC class I and II antigen can be detected in these spinal cords as well, but not in cells with the typical morphology of astrocytes. TNF-alpha, IL-6, and iNOS are also evident in the brains of mice with MHV-induced acute encephalitis, but in marked contrast to the results obtained with the chronically infected mice, most of the cells expressing these cytokines or iNOS had the morphology of macrophages or other mononuclear cells and very few appeared to be astrocytes. Additionally, astrocytes and, most likely, oligodendrocytes are infected in the spinal cords of mice with chronic demyelination. These results are consistent with a role for both viral infection of glial cells and high localized revels of proinflammatory cytokines and nitric oxide in the demyelinating process in mice infected with MHV-JHM. They also show that analogously to the human demyelinating disease, multiple sclerosis, astrocytes are a major cellular source for these cytokines in mice with chronic, but not acute disease. (C) 1995 Academic Press, Inc.
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页码:482 / 493
页数:12
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