Functional correlates of nicotine administration: similarity with drugs of abuse.

i.f. (2001) 3.49

Anti-beta 2-glycoprotein I antibodies bind to central nervous system.

Anti-beta 2-GPI antibodies (a beta 2-GPI) were found in serum from patients with anti-phospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). Since a beta 2-GPI are often found in patients with anti-cardiolipin antibodies (aCL), their role in thrombosis as well as other central nervous system (CNS) manifestations in APS is unclear. We, therefore, investigated whether affinity-purified a beta 2-GPI bind the CNS. Astrocyte and neuron cell lines and histological sections were used as CNS substrates. Indirect immunofluorescence and/or streptavidin-biotin-peroxidase techniques revealed that astrocytes, neurons and vascular endothelium were bound by purified a beta 2-GPI (mouse monoclonal, rabbit polyclonal, human serum Ig a beta 2-GPI). This suggests a potential role for a beta 2-GPI in the CNS damage, as a beta 2-GPI might contribute to CNS pathology by either a direct interaction with astrocytes and neurons or an interaction with cerebral vascular endothelial cells. CNS immunoreaction was also demonstrated using six a beta 2-GPI-positive sera from patients (four with neurological manifestations). No binding to CNS was seen using a beta 2-GPI-negative sera, i.e. five from SLE patients (two with CNS involvement) and six healthy donors, or a monoclonal aCL without a beta 2-GPI immunoreactivity. Thus, the CNS reactivity by the a beta 2-GPI-positive sera appears specifically due to a beta 2-GPI and independent from aCL. Because of the presence of aCL in all patient sera, and the CNS involvement in three control patients, it is not possible to attribute a direct role for a beta 2-GPI in neurological diseases in this study

Effect of human T lymphotropic retrovirus-I exposure on cultured human glioma cell lines

Four different human tumor cell lines of glial origin have been exposed to a human T lymphotropic retrovirus (HTLV-I). All these cell lines were positive for the glial marker glial fibrillary acidic protein (GFAP). The presence of virus RNA was demonstrated by in situ hybridization using an HTLV-I, SStI-SStI viral insert as probe. Virus expression has been monitored through an indirect immunofluorescence assay using a monoclonal antibody against virus core protein p19. All the four glioma cell lines tested became positive for p19 after 2 weeks of co-cultivation and showed a clear alteration of GFAP expression

Effect of human T lymphotropic retrovirus-I exposure on cultured human glioma cell lines

Four different human tumor cell lines of glial origin have been exposed to a human T lymphotropic retrovirus (HTLV-I). All these cell lines were positive for the glial marker glial fibrillary acidic protein (GFAP). The presence of virus RNA was demonstrated by in situ hybridization using an HTLV-I, SStI-SStI viral insert as probe. Virus expression has been monitored through an indirect immunofluorescence assay using a monoclonal antibody against virus core protein p19. All the four glioma cell lines tested became positive for p19 after 2 weeks of co-cultivation and showed a clear alteration of GFAP expression

Transient HTLV-I infection of a human glioma cell line following cell-free exposure

The human T-lymphotropic virus type I (HTLV-I) has been recently associated with cases of tropical spastic paraparesis and human myelopathy. In order to study whether cells of neuroectodermic origin were susceptible to HTLV-I infection, a human glioma cell line T67 was exposed in vitro to HTLV-I by a cell-free method of virus transmission. The presence of HTLV-I proviral DNA was analyzed by polymerase chain reaction 3, 7, and 14 days after infection. The results showed the presence of LTR, pol, and tax sequences within glioma cell line 3 days after the infection. However after 7 and 14 days, detection of HTLV-I sequences remarkably decreased. P19 expression peaked 7 days after infection and decreased in the following week. These data provide evidence that cell-free transmission of HTLV-I results in transient infection of cells of glial origin

CORRELATION BETWEEN P19-PRESENCE AND MHC CLASS-II EXPRESSION IN HUMAN FETAL ASTROGLIAL CELLS COCULTURED WITH HTLV-I DONOR CELLS

The possibility of a direct infection of human brain by HTLV-I, has been studied using an in vitro model. Human fetal astroglial cells were cocultivated with irradiated HTLV-I donor cell line MT-2, and assayed for the presence of HTLV-I core protein p19 after 1 week. Fifty-six per cent of GFAP positive astrocytes showed the viral core protein p19 and increased expression of Class II MHC antigens. Electron microscopy of astroglial cells exposed to HTLV-I revealed the presence of vacuoli-like structures containing viral core protein p19. Cell intermediate filament cytoskeleton was also disorganized. Even if this study does not provide direct evidence for virus replication inside astroglial cells, all these findings suggest that HTLV-I can indeed enter the cell and exert a cytopathic effect. Therefore the results of the present study are consistent with the hypothesis that astroglial cells could be involved in demyelination processes occurring in the HTLV-I associated neurological disorders, such as human associated myelopathy and tropical spastic paraparesis