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Lab Invest. 1996 Jul;75(1):109-23.

Multiple sclerosis: a protective or a pathogenic role for heat shock protein 60 in the central nervous system?

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  • 1Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.

Abstract

The stress proteins belonging to the heat shock protein 60 (hsp6O) family of molecular chaperones with known immunogenic properties are expressed at increased levels in a number of autoimmune conditions. Because previous studies from this laboratory suggested that hsp6O may be involved in the pathogenesis of the chronic multiple sclerosis (MS) plaque, we have examined autopsied central nervous system tissue from 10 cases of MS, ranging in clinical history from acute to chronic inactive. MS lesions ranged from acute, actively demyelinating and edematous, to fibrous astrogliotic and chronically demyelinated. As controls, central nervous system tissue from other neurologic diseases and nonneurologic conditions was used. Frozen, paraffin, and epoxy-embedded sections were studied immunocytochemically with the ML30 mAb to hsp6O. Acute MS lesions displayed the greatest reactivity, with particularly prominent staining of hypertrophic astrocytes, reactive macrophages, and hyperplastic oligodendrocytes. In all these cells, elevated expression occurred in the constitutive site for hsp6O (mitochondria) and within the cytosol, which is suggestive of a shift in expression. The hsp6O-reactive oligodendrocytes were structurally intact. Chronic active MS lesions also revealed the highest levels of hsp6O in hypertrophic astrocytes and oligodendrocytes. Chronic silent MS lesions displayed elevated hsp6O in hypertrophic astrocytes only while constitutive expression occurred elsewhere in the central nervous system at levels slightly higher than normal. Other neurologic disease tissue displayed expression elevated above that found in nonneurologic cases, but this was considerably less than that seen in acute MS. Of the other neurologic diseases, AIDS encephalitis revealed the greatest activity for hsp6O, with both mitochondrial and cytosolic staining of astrocytes. It is proposed that the high levels of hsp6O in hyperplastic, structurally intact oligodendrocytes in acute MS lesions may bespeak a protective mechanism, whereas hsp6O in chronic active lesions may serve a pathogenic role in the later depletion of these cells.

PMID:
8683935
[PubMed - indexed for MEDLINE]
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