Proinflammatory Phenotype and Increased Caveolin-1 in Alveolar Macrophages with Silenced CFTR mRNA

The inflammatory milieu in the respiratory tract in cystic fibrosis (CF) has been linked to the defective expression of the cystic transmembrane regulator (CFTR) in epithelial cells. Alveolar macrophages (AM), important contibutors to inflammatory responses in the lung, also express CFTR. The present study analyzes the phenotype of human AM with silenced CFTR. Expression of CFTR mRNA and the immature form of the CFTR protein decreased 100-fold and 5.2-fold, respectively, in AM transfected with a CFTR specific siRNA (CFTR-siRNA) compared to controls. Reduction of CFTR expression in AM resulted in increased secretion of IL-8, increased phosphorylation of NF-κB, a positive regulator of IL-8 expression, and decreased expression of IκB-α, the inhibitory protein of NF-κB activation. AM with silenced CFTR expression also showed increased apoptosis. We hypothesized that caveolin-1 (Cav1), a membrane protein that is co-localized with CFTR in lipid rafts and that is related to inflammation and apoptosis in macrophages, may be affected by decreased CFTR expression. Messenger RNA and protein levels of Cav1 were increased in AM with silenced CFTR. Expression and transcriptional activity of sterol regulatory element binding protein (SREBP), a negative transcriptional regulator of Cav1, was decreased in AM with silenced CFTR, but total and free cholesterol mass did not change. These findings indicate that silencing of CFTR in human AM results in an inflammatory phenotype and apoptosis, which is associated to SREBP-mediated regulation of Cav1

Image de la réglementation de la vitesse et position sociale dans le système de circulation routière

Between 1970 and 1973, road safety in France took on a new political and social importance with the creation of Inter-ministerial Organisms (an interdepartmental government body consisting of a commission and a special safety delegation) and the adoption of three broad measures: setting of a maximum legal blood alcohol content, compulsory wearing of seat belts, speed limit throughout the road network. This last measure is perhaps a kind of borderline case which bears directly on one of the most basic characteristics of the automobile - that is, its "performance" - and will in all probability give rise to very important changes in the use and image of the private automobile. The different aspects of this problem are dealt with in this article, first from the point of view of the methods used, then with respect to the role of social attitudes and hierarchy in road traffic. This last aspect is concerned with social attitudes to speed regulation, the causes of road accidents, road hazards and lack of safety - in other words, the consensus of opinion on automobile use.Au cours des années 1970-1973, la sécurité routière en France prend une dimension politique et sociale de premier plan avec la création d'organismes Interministériels (Mission puis Délégation à la sécurité routière) et l'adoption de 3 grandes mesures : taux légal d'alcoolémie, port obligatoire de la ceinture de sécurité, limitation de vitesse sur tout le réseau routier. Cette dernière mesure apparaît comme une sorte de cas limite ayant une incidence directe sur l'une des caractéristiques fondamentales de l'automobile, ses "performances", et devrait logiquement entraîner des modifications profondes de l'usage et de l'image de l'automobile individuelle. Les différents aspects de ce problème sont abordés dans cet article au niveau des principes méthodologiques puis sur celui des représentations sociales et positions dans le système de la circulation routière. Ce dernier aspect implique les problèmes de l'attitude à l'égard de la réglementation de la vitesse, l'image des causes de l'accident de la route, le risque et l'insécurité, enfin le consensus quant à l'usage de d'automobile

Effects of EDCs in a wild gudgeon population (Gobio gobio L.) in Luxembourg

For many decades human activities have dispersed toxic chemical substances in the environment. Over the last years new xenobiotics such as endocrine disrupting chemicals (EDCs), antibiotics or nano-particles have appeared. In order to assess the health of river ecosystems in relation to this increasing pressure, twenty sites contaminated at different levels were sampled by electrofishing across the Luxembourg hydrographical network. The status of fish communities was characterized according to an index of biotic integrity (IBI). Furthermore, on six sites, population structure, reproductive parameters and biochemical assays were performed on gudgeon (Gobio gobio) as sentinel species. Stress factor responses were observed at different levels of biological organization: from molecule up to fish communities. At one site, male gudgeons exhibited high levels of plasmatic VTG. Histological examinations revealed high alterations of the gonads: feminization of the testes and high incidence of atresia in ovary. No significant difference in the level of plasmatic VTG was noticed between intersex and non-intersex fish. Conversely, the incidence of atresia seems to be linked with VTG synthesis in female gudgeons. Weight index of the liver also highlighted an exposure to EDCs. More surprisingly, no impairment of the gudgeon population was pointed out. This study provides interesting data concerning endocrine disruption and their higher-level effects of the biological organisation in a wild fish population inhabiting Luxembourg's rivers. Factors potentially leading to alterations of the reproductive tract and more generally to a reduced fertility seem to be diverse and varied, and not exclusively VTG-dependent. By using a multiparametric and multiscale approach, a better understanding of response mechanisms to pollution in fish may be achieved and help improving the ecological status of river ecosystems

Histiocytosis X arising in Hodgkin's disease: immunophenotypic characterization with a panel of monoclonal antibodies

This report describes the antigenic profile of the proliferating cells of pulmonary histiocytosis X (HX) in a patient treated with chemotherapy for Hodgkin's lymphoma; the association of pulmonary HX and Hodgkin's disease has rarely been described in the literature. The histopathological diagnosis of HX was confirmed with the aid of monoclonal antibodies (mAbs) to CD4, CD1a, and polyclonal serum anti S-100 protein. The phenotype of HX cells has been analysed using a panel of mAbs against HLA class I A, B, C monomorphic determinants, locus A and B, beta 2-microglobulin, HLA class II distinct monomorphic determinants, DP, DQ, DR, intercellular adhesion molecule-1 (ICAM-1) and vitronectin receptors. Our results indicate that HX cells express HLA class I and II, including locus A, locus B and DP, DQ, DR, like their normal counterpart (represented by Langerhans cells) and detectable levels of ICAM-1 but not vitronectin receptors. We would like to stress the possibility of the association of HX and Hodgkin's lymphoma extending the immunophenotypic profile of HX cells