Clusterin expression in follicular dendritic cells associated with prion protein accumulation.
Peripheral accumulation of abnormal prion protein (PrP) in variant Creutzfeldt-Jakob disease and some animal models of transmissible spongiform encephalopathies (TSEs) may occur in the lymphoreticular system. Within the lymphoid tissues, abnormal PrP accumulation occurs on follicular dendritic cells (FDCs). Clusterin (apolipoprotein J) has been recognized as one of the molecules associated with PrP in TSEs, and clusterin expression is increased in the central nervous system where abnormal PrP deposition has occurred. We therefore examined peripheral clusterin expression in the context of PrP accumulation on FDCs in a range of human and experimental TSEs. PrP was detected immunohistochemically on tissue sections using a novel highly sensitive method involving detergent autoclaving pretreatment. A dendritic network pattern of clusterin immunoreactivity in lymphoid follicles was observed in association with the abnormal PrP on FDCs. The increased clusterin immunoreactivity appeared to correlate with the extent of PrP deposition, irrespective of the pathogen strains, host mouse strains or various immune modifications. The observed co-localization and correlative expression of these proteins suggested that clusterin might be directly associated with abnormal PrP. Indeed, clusterin immunoreactivity in association with PrP was retained after FDC depletion. Together these data suggest that clusterin may act as a chaperone-like molecule for PrP and play an important role in TSE pathogenesis.
Sasaki
K
K
Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. ksasaki@np.med.kyushu-u.ac.jp
Doh-ura
K
K
Ironside
Jw
J
Mabbott
N
N
Iwaki
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D051152:Clusterin / Q000032:analysis*; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism*; D020566:Dendritic Cells, Follicular / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015850:Interleukin-6 / Q000235:genetics; D008221:Lymphoid Tissue / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008875:Middle Aged; D018832:Molecular Chaperones; D018620:PrPSc Proteins / Q000032:analysis / Q000378:metabolism*
D015415:Biomarkers; D051152:Clusterin; D015850:Interleukin-6; D018832:Molecular Chaperones; D018620:PrPSc Proteins