We recently reported that sera of NOD mice contain autoantibodies to the endogenous HSP60. Under physiological conditions, the HSP60 antigen was located to secretory granules and mitochondria of β-cells, but in islets affected by insulitis, the antigen accumulated rapidly in cytoplasm and on β-cell surface membranes. The relationship was examined between insulitis-dependent redistribution of the HSP60 inside β-cells and induction of the HSP60 autoantibodies. By use of quantitative immunoelectron microscopy and monoclonal antibodies to human HSP60, changes were monitored in levels of the cytoplasmic HSP60 with progression of insulitis. Development of insulitis was accompanied by reduction of the HSP60 levels in secretory granules and increased levels in the cytoplasm. Mean concentration of cytoplasmic HSP60 in 4-, 7-, and 13-wk-old NOD mice representing 0, 85, and 100% incidence of insulitis, gradually increased from 4.6 to 11.2 to 35.9 immunogold grains/μm2, respectively, and this increase was statistically significant (P < 0.001). Simultaneously, the time course of an appearance of HSP60 antibodies was established by testing sera of > 4- to 25-wk-old NOD mice, for their cross-reactivity to human recombinant HSP60 on Western blots. HSP60 antibodies developed in both sexes between 7 and 13 wk of age but were found with the highest frequency in sera of 10- to 15-wk-old mice. Antibodies declined rapidly with the onset of diabetes. HSP60 antibodies were not observed in sera of 4-wk-old NOD mice devoid of insulitis or in 7-wk-old males with delayed onset of insulitis. The cytoplasmic HSP60 levels in these cases were the same as in control mice. These data suggest that insulitis is a causative factor in the HSP60 redistribution, and that this HSP60 redistribution inside the β-cells is temporarily associated with the induction of the humoral autoimmune response to the HSP60.
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Original Articles| June 01 1993
Insulitis-Caused Redistribution of Heat-Shock Protein HSP60 Inside β-cells Correlates With Induction of HSP60 Autoantibodies
Address correspondence and reprint requests to Dr. Katrina Brudzynski, Robarts Research Institute, University of Western Ontario, 100 Perth Drive, London, Ontario, Canada N6A 5K8.
Katrina Brudzynski; Insulitis-Caused Redistribution of Heat-Shock Protein HSP60 Inside β-cells Correlates With Induction of HSP60 Autoantibodies. Diabetes 1 June 1993; 42 (6): 908–913. https://doi.org/10.2337/diab.42.6.908
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