Cell culture isolation of a transmissible cytotoxicity from a human sample of cerebrospinal fluid.
We investigated a transmissible cytotoxicity isolated in VERO cell cultures from a sample of cerebrospinal fluid (CSF) drawn from a woman with ischemic brain injury. Amorphous aggregates formed by subunities of approximately 11 nm of diameter were detected in ultracentrifugates from partially purified cytotoxic cell preparations in the absence of virion-like particles which might justify the trasmissibility of this cytotoxic activity. Results of chemico-physical studies provided indications on the presence in the CSF of two protease-resistant acidic glycoproteins of about 39 and 27 kDa, respectively. The conformational change of a proteinic molecule may associate with particular properties such as tendency to aggregation, resistance to proteolysis, cytotoxicity. Considering that these same properties are shared by proteins present in the CSF sample under study, a hypothesis to pursue is that the CSF inoculum we isolated contained misfolded proteins formed in vivo following the ischemic injury of brain tissue. As far as the in vitro transmissibility of the cytotoxic activity, this could take place following the reproduction of the alterations of those proteins, independently of the original cause(s) which have fostered their formation in vivo.
Portolani
Marinella
M
Centre for Diagnosis of Viral Diseases, Department of Laboratory Medicine, University Hospital of Modena and Reggio Emilia via del Pozzo, 71-41100 Modena, Italy. portolani.matinella@unimo.it
Beretti
Francesca
F
Cermelli
Claudio
C
Bartoletti
Anna M
AM
Pietrosemoli
Paola
P
Bargellini
Annalisa
A
De Pol
Anto
A
Rossini
Gian Paolo
GP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods*; D002458:Cell Fractionation / Q000379:methods; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D002556:Cerebrospinal Fluid Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity; D002522:Chlorocebus aethiops; D002852:Chromatography, Ion Exchange / Q000379:methods; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000633:toxicity; D053938:DNA Fragmentation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D006801:Humans; D007511:Ischemia / Q000134:cerebrospinal fluid*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D013997:Time Factors
D002556:Cerebrospinal Fluid Proteins; D003603:Cytotoxins