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Pathogenesis of pulmonary disease

Final Activity Report Summary - PULMO-NET (Pathogenesis of pulmonary disease)

The project was created with the aim to improve methodological approaches to study lung function and dysfunction on a cellular and molecular level, gaining a better understanding of normal lung function, toxicity of environmental compounds, cell and tissue damage and generation of pulmonary disease. Beyond this scientific aspect, training and transfer of knowledge aimed at offering a broad pulmonary and respiratory biology education to PhD students and post-docs, at disseminating the results to the scientific community and at establishing long-term collaborations within the network and with industrial and academic partners. PULMO-NET consisted of 5 academic institutions, one European joint research centre (JCR Ispra, Center for Validation of Alternative Methods) and one industrial partner (Across barriers GmbH, Saarbrücken). The former were the Universities of Ulm, Innsbruck, Konstanz, Paris Sud and Complutense de Madrid.

PULMO-NET was successful in all these goals. Scientifically, the network published several joint publications in high ranking, peer-reviewed scientific journals. These papers contain progress in pulmonary cell culture, in particular new cell models and culture methods suitable for the investigation and assessment of epithelial secretion and transport, several new techniques to study the function of type II alveolar cells and their secretory products, in particular surfactant, the characterization of signalling pathways and metabolites, in particular the interactions of endotoxins and inflammatory mediators with purinergic signalling, lung toxicity effects on epithelial barrier function and finally, morphological and functional analysis of cellular responses to stretch or other forms of mechanical stress. Altogether, these data yield a far better understanding than we had before about pathogenic principles that may result in hyperventilation-induced lung injury, toxicity of heavy metals, acute lung dysfunction (edema, respiratory distress) and generation of inflammatory responses, possibly long-term remodelling (fibrosis, COPD, emphysema).

Methodological progress and development of new techniques resulted not only in publications, but also in pending patents and new collaborations with industrial partners. As an example, new advanced cell culture techniques including cell growth on permeable supports at the air-liquid interface resulted in a new project involving drug testing and development with Boehringer Ingelheim, Germany. New cell stretch devices will be further used to obtain insight into cellular and molecular mechanisms of hyperventilatio-induced lung injury. A new captive bubble device (patent pending) will be used to study the surface characteristics of native and artificial surfactants, aiming at developing better therapeutic strategies against immature lungs of new-born babies (infant respiratory distress syndrome).

PULMO-NET was very active in organising workshops, meetings and congresses that were partially open to the public, partially specifically designed to improve training of researchers employed by the project. The latter consisted of five workshops organised by five of the entire seven partners institutions of PULMO-NET, and addressed the following topics:
- microscopy and live cell imaging (Ulm);
- surface biophysics and measurement of surface tension (Madrid);
- cell culture (Innsbruck);
- validation of methods (JRC, Ispra); and
- project management and leadership (Saarbrücken).
These workshops trained between 10 and 15 researchers employed by the project.

PULMO-NET organised four annual meetings, two of which were open to the public (Saarbrücken 2008 and Innsbruck 2009). The final congress in Innsbruck was entitled 'Cellular and molecular biology of the pulmonary alveolar epithelium in health and disease' (please see http://www.PULMO-NET-congress.de online) 23 invited speakers, all top experts in this field, presented new information on ion transport, fluid balance and barrier function, endocytosis, exocytosis, trafficking, surfactant processing, mechanotransduction, cellular injury, inflammation, repair, differentiation, intra- and intercellular signal transduction, air-liquid interface phenomena, defence, drug delivery, nanoparticles.