CD8-positive T cells are thought to play an important role in the control of infection by human immunodeficiency virus (HIV) as a result of their cytotoxic activity and by releasing soluble factors. In AIDS patients, the absolute number of CD8+ T lymphocytes is decreased in peripheral blood and their turnover rate is increased, suggesting that there is more cell renewal and cell death occurring. Anti-retroviral therapy raises CD8+ T-cell counts in HIV-infected patients. Here we report that the death rate of CD8+ T cells by apoptosis increased markedly during HIV infection of peripheral blood mononuclear cells in vitro. Apoptosis is induced in a dose-dependent manner by recombinant envelope glycoprotein gp120 from HIV strain X4, or by stromal-derived factor-1 (SDF-1), the physiological ligand of the chemokine receptor CXCR4. Apoptosis is mediated by the interaction between tumour-necrosis factor-alpha bound to the membrane of macrophages (mbTNF) and a receptor on CD8+ T cells (TNF-receptor II, or TNFRII). The expression of both of these cell-surface proteins is upregulated by HIV infection or by treatment with recombinant gp120 or SDF-1. Apoptosis of CD8+ T cells isolated from HIV-infected patients is also mediated by macrophages through the interaction between mbTNF and TNFRII. These results indicate that the increased turnover of CD8+ T cells in HIV-infected subjects is mediated by the HIV envelope protein through the CXCR4 chemokine receptor.
GH3/B6 rat pituitary tumor cells exhibit rapid prolactin release (within 5 min) when treated with nanomolar amounts of estrogen. However, the putative protein mediator of this nongenomic action has not been described. Using antibodies directed against a peptide representing the hinge region of the intracellular estrogen receptor (iER), we have demonstrated that these cells contain a membrane ER (mER). We now report that confocal scanning laser microscopy of cells labeled live with the anti-peptide antibody further supports a membrane localization of ER. The monoclonal antibodies H226 and H222 and a polyclonal antibody, ER21, each recognizing a unique epitope on iER (NH2 terminal to the DNA-binding region, within the steroid binding region, and the NH2-terminal end, respectively), also immunohistochemically label membrane proteins of immuno-selected GH3/B6 cells. These cells also specifically bind a fluorescent estrogen-BSA conjugate. Coincubation of cells with anti-ER antibody and the fluorescent estrogen-BSA conjugate reveals that these labels colocalize on cells. These results suggest that mER may be structurally similar to iER.
The remarkable optical and electrical properties of nanostructured materials are considered now as a source for a variety of biomaterials, biosensing, and cell interface applications. In this study, we report the first example of hybrid bionanodevice where absorption of light by thin films of quantum confined semiconductor nanoparticles of HgTe produced by the layer-by-layer assembly stimulate adherent neural cells via a sequence of photochemical and charge-transfer reactions. We also demonstrate an example of nanoscale engineering of the material driven by biological functionalities.
Single-walled carbon nanotubes (SWNTs) have a set of unique mechanical and electrical properties that has stimulated tremendous interest in them. Significant efforts have been directed towards utilizing these materials as building blocks of composites for a variety of technological contexts, such as nanoelectronic devices, [1][2][3][4][5][6] sensors, [7][8][9][10][11][12] and field emission electron displays and lighting elements. [13,14] We strongly believe that one of the most prolific areas of their applications will be in biomedicine, where compact, strong, and high-performance devices can be engineered. These devices will exploit the properties of SWNTs and will compete with existing products. The novel technologies of diagnostics and therapeutics can be based on SWNT composites and individual tubes. Along these lines, SWNTs have been demonstrated as potential sensing materials of biological systems, [15][16][17][18][19] which are typically considered for the use in ex vivo modality. The potential use of SWNT-based structures for the purpose of healing neurological and brain-related injuries represents one of the major scientific and practical interests. The high mechanical strength and electrical properties possessed by SWNTs makes these materials perfect candidates for various prosthetic devices, including bone and joint repair. It is important to realize, however, that successful utilization of SWNT-based devices in biomedicine is hinged on the ability of such materials to interface with living cells, support their growth, and at the same time preserve their viability. [20][21][22][23][24] These factors are not well understood for any SWNT structures, which limits the development of in vivo, that is, implantable devices from such materials. The actual processes and techniques used for the preparation of macroscopic objects from SWNTs will play a significant role in determining cellular effects of SWNT composites. Substrates prepared from multi-walled carbon nanotubes (MWNTs) as well as SWNTs have been reported to be biocompatible platforms for neuronal growth and differentiation. [25][26][27] The use of carbon nanofiber composites as devices for neural-and bone-tissue-implant integration has also been described.[28] Molecular engineering of any SWNT-based composite should have a great effect on how the material performs during long-term contact with tissue. The layer-by-layer (LBL) approach to prepare SWNT structures can be particularly useful in this respect because it allows one to exert control over the structure of the SWNT/polymer systems from angstrom to nanometer and micrometer scale, which is necessity for the engineering of the cell/SWNT interface. [29] Recently, we demonstrated that SWNT LBL films can support the growth, viability, and differentiation of neuronal NG108-15 neuroblastoma/glioma hybrid cells. [30] The first example of free-standing SWNT/polymer thin-film membranes that can be mechanically compatible with tissues and can be used as implants and repair devices for neurological-or bra...
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