MULTIPLE-SCLEROSIS - A PROTECTIVE OR A PATHOGENIC ROLE FOR HEAT-SHOCKPROTEIN-60 IN THE CENTRAL-NERVOUS-SYSTEM

The stress proteins belonging to the heat shock protein 60 (hsp60) fam ily of molecular chaperones with known immunogenic properties are expr essed at increased levels in a number of autoimmune conditions. Becaus e previous studies from this laboratory suggested that hsp60 may be in volved in the pathogenesis of the chronic multiple sclerosis (MS) plaq ue, we have examined autopsied central nervous system tissue from 10 c ases 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, cen tral nervous system tissue from other neurologic diseases and nonneuro logic conditions was used. Frozen, paraffin, and epoxy-embedded sectio ns were studied immunocytochemically with the ML30 mAb to hsp60. Acute MS lesions displayed the greatest reactivity, with particularly promi nent staining of hypertrophic astrocytes, reactive macrophages, and hy perplastic oligodendrocytes. In all these cells, elevated expression o ccurred in the constitutive site for hsp60 (mitochondria) and within t he cytosol, which is suggestive of a shift in expression. The hsp60-re active oligodendrocytes were structurally intact. Chronic active MS le sions also revealed the highest levels of hsp60 in hypertrophic astroc ytes and oligodendrocytes. Chronic silent MS lesions displayed elevate d hsp60 in hypertrophic astrocytes only while constitutive expression occurred elsewhere in the central nervous system at levels slightly hi gher than normal. Other neurologic disease tissue displayed expression elevated above that found in nonneurologic cases, but this was consid erably less than that seen in acute MS. Of the other neurologic diseas es, AIDS encephalitis revealed the greatest activity for hsp80, with b oth mitochondrial and cytosolic staining of astrocytes. It is proposed that the high levels of hsp60 in hyperplastic, structurally intact ol igodendrocytes in acute MS lesions may bespeak a protective mechanism, whereas hsp80 in chronic active lesions may serve a pathogenic role i n the later depletion of these cells.