Objectif i) To determine the molecular mechanisms of interaction between environment-polluting metals and the cells of the immune system;ii) To determine the role of the genes (e.g. human leukocyte antigen (HLA) genes) which regulate the response of the cells of the immune system (e.g. T-lymphocytes) to foreign agents;iii) To assess the predictive value of HLA-associated DNA markers for the prevention of environment-induced lung disorders by the screening of exposed populations for susceptibility to allergy to metals.Epidemiologic, clinical and immunologic studies have demonstrated that metals are capable of inducing lung allergy, including asthma, pneumonitis and chronic interstitial lung diseases. Allergy to metals such as gold, nickel and beryllium is maintained by specialized immune cells, i.e. the T-lymphocytes, which specifically recognize these foreign agents and drive the lung reaction against them.The molecular basis of allergy to metals will be investigated as follows:i) The mechanisms of recognition of metals by T-lymphocytes will be characterized using permanent T-lymphocyte lines derived from individuals with allergy to metals.ii) The molecular mechanisms by which HLA-genes dictate the recognition of metals by T-lymphocytes, will be determined using purified HLA molecules and genetically engineered HLA molecule-expressing cells, to identify genetic markers useful in predicting and preventing metal allergy in susceptible individuals.iii) HLA gene association with the allergy to metals will be determined by analysis of gene frequencies in populations of individuals affected by allergy to metals.iv) Based upon data obtained from population studies and in vitro experiments, the ability of the HLA-related DNA markers to predict the risk of susceptibility to metal-induced allergy will be evaluated in a pilot study on metal-exposed individuals.The study is expected to identify the mechanisms of interaction between environmental factors and genetic factors involved in susceptibility to metal-induced allergy. Consequently, it will permit to design new genetic testing protocols for:i) The identification of risk factors involved in environment-related lung disorders;ii) The screening of exposed populations to identify susceptible individuals. Champ scientifique medical and health sciencesclinical medicinepneumologyasthmanatural sciencesbiological sciencesgeneticsDNAnatural scienceschemical sciencesinorganic chemistryalkaline earth metalsmedical and health sciencesbasic medicineimmunologymedical and health sciencesclinical medicineallergology Programme(s) FP3-ENV 1C - Specific research and technological development programme (EEC) in the field of the environment, 1990-1994 Thème(s) 040203 - Environment and human health Appel à propositions Data not available Régime de financement CSC - Cost-sharing contracts Coordinateur Università degli Studi di Modena Contribution de l’UE Aucune donnée Adresse Via del Pozzo 71 41100 Modena Italie Voir sur la carte Coût total Aucune donnée Participants (3) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire MRC Clinical Sciences Centre Royaume-Uni Contribution de l’UE Aucune donnée Adresse Hammersmith Hospital Du Cane Road W12 0NN London Voir sur la carte Coût total Aucune donnée UNIVERSITY OF ROME "LA SAPIENZA" Italie Contribution de l’UE Aucune donnée Adresse Piazzale Aldo Moro 5 00185 ROMA Voir sur la carte Coût total Aucune donnée Università degli Studi di Bari Italie Contribution de l’UE Aucune donnée Adresse Piazza Giulio Cesare 70124 Bari Voir sur la carte Coût total Aucune donnée
