Ascorbic acid pre-treated quartz stimulates TNF-α release in RAW 264.7 murine macrophages through ROS production and membrane lipid peroxidation

<p>Abstract</p> <p>Background</p> <p>Inhalation of crystalline silica induces a pulmonary fibrotic degeneration called silicosis caused by the inability of alveolar macrophages to dissolve the crystalline structure of phagocytosed quartz particles. Ascorbic acid is capable of partially dissolving quartz crystals, leading to an increase of soluble silica concentration and to the generation of new radical sites on the quartz surface. The reaction is specific for the crystalline forms of silica. It has been already demonstrated an increased cytotoxicity and stronger induction of pro-inflammatory cyclooxygenase-2 (COX-2) by ascorbic acid pre-treated quartz (QA) compared to untreated quartz (Q) in the murine macrophage cell line RAW 264.7.</p> <p>Methods</p> <p>Taking advantage of the enhanced macrophage response to QA as compared to Q particles, we investigated the first steps of cell activation and the contribution of early signals generated directly from the plasma membrane to the production of TNF-α, a cytokine that activates both inflammatory and fibrogenic pathways.</p> <p>Results</p> <p>Here we demonstrate that TNF-α mRNA synthesis and protein secretion are significantly increased in RAW 264.7 macrophages challenged with QA as compared to Q particles, and that the enhanced response is due to an increase of intracellular ROS. Plasma membrane-particle contact, in the absence of phagocytosis, is sufficient to trigger TNF-α production through a mechanism involving membrane lipid peroxidation and this appears to be even more detrimental to macrophage survival than particle phagocytosis itself.</p> <p>Conclusion</p> <p>Taken together these data suggest that an impairment of pulmonary macrophage phagocytosis, i.e. in the case of alcoholic subjects, could potentiate lung disease in silica-exposed individuals.</p

E-procurement and its impact on supply management - evidence from industrial case studies

Many buying firms have adopted e-procurement systems, yet the impact of these applications is still being assessed by both academics and practitioners alike. This paper examines the use of e-procurement within four multinational firms, to establish the impact of these mechanisms on their approach to the supply market, using thematic parameters derived from the literature. The results indicate that these firms established a clear supply market strategy based on a segmentation model: e-procurement tools were used as tactical means to implement and extend that strategy towards the supply base. In addition, it was observed that tactics within defined segments are developing, as buying firms use e-procurement tools both to reduce supplier numbers and to leverage their volumes in price- competitive markets. Various propositions are offered on the key themes, summarising the findings in the paper and providing further indications for research

Religioni e democrazia nel processo di globalizzazione

Il contributo illustra il ruolo delle religioni nel processo di globalizzazione, con particolare riferimento alla "globalizzazione" del sistema democratico