Experimental autoimmune encephalomyelitis. Qualitative and semiquantitative differences in heat shock protein 60 expression in the central nervous system.
The factors that contribute to disease progression in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are not known. In this study, we have tested the hypothesis that inflammation in the central nervous system (CNS) is associated with altered expression of heat shock proteins (hsp) that may function as a target in the development of chronic disease. In normal mouse spinal cord, hsp 60 immunoreactivity was localized exclusively to its constitutive site in mitochondria. In animals with acute EAE, lesions were accentuated by increased expression of hsp 60, primarily by infiltrating cells. In chronic EAE, hsp 60 was found predominantly on CNS components, particularly oligodendrocytes, and astrocytes. In both acute and chronic lesions, hsp 60 was located in the cytoplasm of cells, but in non-lesion areas, it was mitochondrial. By semiquantitative Western blotting, hsp 60 in normal mouse spinal cord (n = 6) was 0.99 +/- 0.09% of total protein. In acute EAE (n = 6), the value was 1.08 +/- 0.1%, and in chronic EAE (n = 8), 1.39 +/- 0.39%. FACS analysis showed that a subpopulation of CD3+ cells expressed hsp 60 on the cell surface, an observation confirmed by cell surface labeling and immunoprecipitation. In chronic EAE lesions, gamma delta T cells colocalized with areas of increased hsp 60 immunoreactivity. The results support the conclusion that development of autoimmune-directed inflammation in the CNS is associated with differences in hsp 60 expression that may act as an additional target and/or modulator of the immune response.
Gao
Y L
YL
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461.
Brosnan
C F
CF
Raine
C S
CS
D000818:Animals; D015153:Blotting, Western; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism*; D018834:Chaperonin 60 / Q000096:biosynthesis*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D011233:Precipitin Tests; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology
D018834:Chaperonin 60; D016692:Receptors, Antigen, T-Cell, gamma-delta