RESUMO
A transmissible cytotoxic agent thought to be associated with one or more misfolded protein(s) was found in several cerebrospinal fluid (CSF) samples from neurological patients. Since some experiments carried out to identify this unusual infectious factor showed the block of its propagation by rabbit gammaglobulins (IgGs), the search for such an activity by human IgGs was programmed. Neutralizing assays carried out using human sera as IgGs source showed a blocking property displayed by: twenty serum samples from as many patients with a diagnosis of acute infection, two of ten sera from healthy subjects and four serum samples from patients with lupus erythematous (SLE). When neutralizing sera were tested on cell cultures in immunofluorescence assays for the serum ability to label specific protein( s), similar fluorescent pictures resulted in treated and control cells. On the other hand, the SLE serum samples disclosed a granulosity of the nuclear material of cytotoxic cells in accordance with the DNA apoptotic laddering reported in previous papers. Oxidative disorders, as suggested by the immunoblotting analysis of the antioxidant enzymes Mn-superoxide dismutase (SOD2) and heme-oxygenase 1 (HO-1), point to an alteration of the oxidative pathway among the causes of the DNA damage induced by the cytotoxic transmissible agent under study.
Assuntos
Isquemia Encefálica/líquido cefalorraquidiano , Isquemia Encefálica/imunologia , Proteínas do Líquido Cefalorraquidiano/imunologia , Testes de Neutralização/métodos , Deficiências na Proteostase/líquido cefalorraquidiano , Deficiências na Proteostase/imunologia , Animais , Isquemia Encefálica/sangue , Células Cultivadas , Proteínas do Líquido Cefalorraquidiano/sangue , Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano , Citotoxinas/sangue , Citotoxinas/líquido cefalorraquidiano , Citotoxinas/imunologia , Fibroblastos/citologia , Fibroblastos/imunologia , Heme Oxigenase-1/sangue , Heme Oxigenase-1/líquido cefalorraquidiano , Humanos , Imunoglobulina G/farmacologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/líquido cefalorraquidiano , Lúpus Eritematoso Sistêmico/imunologia , Neuroglia/citologia , Neuroglia/imunologia , Estresse Oxidativo/fisiologia , Deficiências na Proteostase/sangue , Coelhos , Superóxido Dismutase/sangue , Superóxido Dismutase/líquido cefalorraquidianoRESUMO
When inoculated into cell cultures to search for cytopathic viruses, six out of 384 cerebrospinal fluid (CSF) samples from patients with different neurological disorders proved to have a transmissible cytotoxic activity (TCA) not correlated to a conventional infectious agents. Properties shown by a TCA previously detected in the CSF sample of a patient with brain ischemia (Portolani et al., 2005) were shared by each of the newly isolated TCAs. We conclude that independently of the neurological clinical picture shown by the patient, the TCA detected in the CSF samples under study could have the same origin.