Experimental studies on the mechanisms of particle-mediated lung disease

• Main Author: Donaldson, Kenneth
• Published: University of Edinburgh 1997
• Subjects: 616.2
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.649626

Section 1: Experimental pathology studies with rats, including lung dose determination studies. These studies, on the pathological responses of rats following inhalation of fibres or particles, were aimed at determining the types of pathological response caused and the characteristics of fibres and particles that dictate their pathogenicity. Additionally the rat peritoneal cavity was used as a model site for studying the development of mesotheliomas in response to fibre exposure. Section 2: Effects of particles on cells <I>in vitro. </I>These studies were carried out in order to dissect the cellular events that lead to pathogenic change in response to particles and utilised macrophages, epithelial cells and mesothelial cells. Studies took the general form of exposing cells in culture to fibres and particles and measuring endpoints that relate to pathogenicity, e.g. pro-inflammatory mediators. Section 3: Studies on inflammatory leukocytes elicited by particles. Study of the characteristics of the inflammatory cells elicited by pathogenic particles are the logical consequence of the studies in Section 3. The general design of these experiments was exposure of rat and mouse lung or peritoneal cavity to particles followed by harvest of the inflammatory cells for examination of various relevant end-points. Section 4: The effects of particles on the immune system. It has been suggested that particles may enhance the immune response, which could promote inflammation and pathological change. The studies in this section describe the impact of particles on the immune system. Section 5: Studies on mesothelial cells and asbestos. There is little information on the mechanism whereby asbestos and other fibres cause the unusual pleural cancer mesothelioma. Studies were therefore carried out using various models to try and understand the cellular basis of the disease.