GD1a modulates GM-CSF-induced cell proliferation

AbstractGangliosides have been extensively described to be involved in the proliferation and differentiation of various cell types, such including hematopoietic cells. Our previous studies on murine models of stroma-mediated myelopoiesis have shown that gangliosides are required for optimal capacity of stromal cells to support proliferation of myeloid precursor cells, being shed to the supernatant and selectively incorporated into myeloid cell membranes. Here we describe the effect of gangliosides on the specific granulocyte–macrophage colony-stimulating factor (GM-CSF)-induced proliferation. For that, we used the monocytic FDC-P1 cell line, which is dependent upon GM-CSF for survival and proliferation. Cells were cultured in the presence of GM-CSF and exogenous gangliosides (GM3, GD1a or GM1) or in the absence of endogenous ganglioside synthesis by the use of a ceramide-synthase inhibitor, d-PDMP. We observed that exogenous addition of GD1a enhanced the GM-CSF-induced proliferation of the FDC-P1 cells. Also, we detected an increase in the expression of the α isoform of the GM-CSF receptor (GMRα) as well as of the transcription factor C/EBPα. On the contrary, inhibition of glucosylceramide synthesis was accompanied by a decrease in cell proliferation, which was restored upon the addition of exogenous GD1a. We also show a co-localization of GD1a and GMR by immunocytochemistry. Taken together, our results suggest for the first time that ganglioside GD1a play a role on the modulation of GM-CSF-mediated proliferative response, which might be of great interest not only in hematopoiesis, but also in other immunological processes, Alzheimer disease, alveolar proteinosis and wherever GM-CSF exerts its effects

An International Service Life Database: The grid Definition for an Actual Implementation of Factor Methods and Service Life Prediction

Service Life planning is becoming more and more important in the design step when the set of taken choices are influenced by the entire life cycle assessment of a building process: as a consequence, the need for more accurate Service Life data becomes essential, compounded by the necessity of a wider availability and an easier accessibility to this information. Due to the resulting increase in the detail and the complexity of building materials and components data, a tool for its collection, sharing and use becomes indispensable. Moreover, the attention towards the sustainable issue should consider building materials and components performance over time since such life-cycle assessment knowledge cannot be crystallized at their initial behaviour. The choice of the best building components and materials to be adopted in each design process has to consider not only their duration but also their failure rate curve over time: an effective sustainable process is based on an optimised maintenance planning and this is possible only through the knowledge of building components’ durability.Such a tool for building materials and components data collection should provide information about their service life in known reference conditions (Reference Service Life, RSL). Furthermore it could be exploited for Service Life Prediction as well: the aim is to structure this database as a collaborative tool to allow the sharing among all the different stakeholders of the building process but, at the same time, to ease development of further implementations, such as the application of methods for Service Life Estimation. This paper presents the methodological research activity employed to create a factor grids database for RSL data collection and for the application of a proposed enhanced factor method for Service Life Prediction