Unaltered apoptotic behaviour of mononuclear cells from patients with sporadic Creutzfeldt-Jakob disease

Abstract

Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible spongiform encephalopathies. It is suspected that a pathologically altered form of the prion protein (PrPSc) is the decisive trigger of the disease. Data from animal experiments suggest an involvement of the lymphatic system in the intracorporal transport of PrPSc. However, it has not so far been possible to detect PrPSc on mononuclear cells (MNCs) either in the sporadic form of CJD or in the new variant of CJD (vCJD). In order to determine a possible alteration of MNCs in CJD, we investigated the natural and induced apoptotic behaviour of these cells. MNCs from 19 patients with sporadic CJD and from 20 patients with other neurological disorders were used. The cells were analysed by fluorescence cytometry with and without apoptosis induction by xanthine oxidase and hypoxanthine. The apoptosis rate was quantified using the stain 7-amino-actinomycin D (7-AAD). In the morphological investigation of the cells before apoptosis induction, there were no significant differences between the groups with regard to cell size and granularity of the MNCs. After apoptosis induction, the typical significant decrease in cell size and increase in granularity of the cells occurred in both groups. Significant differences between the patient populations were not found. For the first time, our investigation has demonstrated that a functional impairment of MNCs with regard to their apoptotic behaviour does not occur in sporadic CJD. It remains open to question whether this mechanism plays an important role in forms of transmissible encephalopathy other than sporadic CJD, especially after oral transmission.

„Ex vivo” Replikation des pathogenen Prion Proteins

“…Infizierte Kulturen wurden auch mit Hilfe der FACS Analyse untersucht. Dabei wurden die reguliert exprimierenden Kulturen mit und ohne Tet kultiviert und mit nicht transfizierten Zellen vor und nach einer Infektion mit BSE verglichen (Ratzka et al, 2001;Simak et al, 2002;Falanga et al, 2005). Dabei wurde festgestellt, dass bei allen infizierten Klonen die Somit konnte gezeigt werden, dass BSE in der Lage ist, über die Speziesbarriere hinweg, verschiedene Arten zu infizieren.…”