Description:

Cytolysins inflict cell damage by forming pores in the plasma membrane. The Na+ conductivity of these pores results in an ion influx that exceeds the capacity of the Na+/K+-pump to extrude Na+. This net load of intracellular osmolytes results in swelling and eventual lysis of the attacked cell. Many nucleated cells have the capacity to reduce the potential damage of pore-forming proteins, whereas erythrocytes have been regarded as essentially defenceless against cytolysin-induced cell damage. This review addresses how autocrine/paracrine signalling and the cells intrinsic volume regulation markedly influence the fate of the cell after membrane insertion of cytolysins. Moreover, it regards the various steps that may explain the relative large degree of diversity between cell types and species as well as highlights some of the current gaps in the mechanistic understanding of cytolysin-induced cell injury. Cell therapy strategies that use adult peripheral blood-derived CD34+ progenitor cells are hampered by low cell numbers and the infrequent cellular incorporation into the neovasculature. Hence, the use of CD34+ cells to treat ischaemic diseases is under debate. Interaction between CD34+ cells and CD14+ cells results in superior endothelial differentiation of CD14+ cells in vitro, indicating that cell therapy approaches utilizing both CD34+ and CD14+ cells may be advantageous in therapeutic neovascularization. Here, human CD34+ and CD14+ cells were isolated from adult peripheral blood and implanted subcutaneously into nude mice, using matrigel as the carrier. Combined implantation of human CD34+ and CD14+ cells resulted in superior neovascularization, compared to either cell type alone, albeit incorporation of human cells into the murine vasculature was not observed. Human CD34+ and CD14+ cells produced and secreted a pentad of pro-angiogenic mediators, such as HGF, MCP-1 and IL-8, bFGF and VEGFa in monoculture. The production and secretion of pro-angiogenic mediators by CD14+ cells was highly amplified upon incubation with conditioned medium from CD34+ cells. In vivo, neovascularization of matrigel implants did not rely on the endothelial differentiation and incorporation of CD34+ or CD14+ cells, but depended on the paracrine effects of IL-8, MCP-1, HGF, bFGF and VEGFa secreted by implanted cells. Administration of this growth factor/cytokine pentad using matrigel as a carrier results in cell recruitment and microvessel formation equal to progenitor cell-induced neovascularization. These data provide new insights on neovascularization by cell therapy and may contribute to new strategies for the treatment of ischaemic diseases.

The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal circadian pacemaker in the brain, co-ordinating the vast array of physiological, behavioural and metabolic daily rhythms that adapt us to the challenges and opportunities presented by our 24 hour world. Advances over the last ca. 15 years have shown that within individual SCN neurons, circadian pacemaking revolves around a cell-autonomous transcriptional/post-translational feedback loop in which period (Per) and cryptochrome (Cry) genes are negatively regulated by their protein products. More recent evidence has indicated, however, that inter-neuronal, cell-cell interactions are just as important as this intra-neuronal molecular cycle. These interactions are poorly understood but they are essential not only for synchronising cellular pacemaking across SCN circuits, but also for maintaining the activity of these core feedback loops within SCN cells. This presentation will review evidence that a hierarchy of paracrine, neuropeptidergic inter-neuronal signals plays an essential role in maintaining the SCN pacemaker. Malignant mesothelioma (MM) cells enhanced proliferation of endothelial cells (ECs) as well as their angiogenesis in vitro by secretion of fibroblast growth factor-2 (FGF2). This effect was suppressed by pre-treating MM cells with α-tocopheryl succinate (α-TOS), which inhibited FGF2 secretion by inducing mitochondria-dependent generation of reactive oxygen species. The role of FGF2 was confirmed by its down-regulation by treating MM cells with siRNA, abolishing EC proliferation and wound healing enhancement afforded by MM cells. We conclude that α-TOS disrupts angiogenesis mediated by MM cells by inhibiting FGF2 paracrine signalling.

With Regards
Sofia
Journal Coordinator
Global Journal of Research and Review