Toxicological, histopathological and proteomic analysis of a polymer-induced lung injury model

Hicks, Martina. 2006. Toxicological, histopathological and proteomic analysis of a polymer-induced lung injury model. PhD Thesis, Cardiff University.

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Abstract

The inhalation of poorly soluble particles such as synthetic resin polymers is characterised by a series of biochemical and histopathological responses in the lung. These responses can be characterised as acute and chronic pathologies that include pulmonary oedema, inflammation and fibrosis. The ability correctly to identify patients that manifest early signs of lung injury could significantly reduce the morbidity from these types of pathologies. Consequently, this study was undertaken to identify protein markers of early oedema and inflammation. Models of pulmonary injury were induced in the rat lung via intratracheal instillation of a synthetic resin polymer. Conventional quantitative analysis of broncho-alveolar lavage (BAL) fluid was used to indicate the severity of the oedematous response, whilst morphological changes were identified by histological examination. Two dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (2D SDS PAGE) was then employed to separate the proteins in the BAL fluid collected from the mild and persistent models of lung injury. The complete toxicological and histological characterisation of the polymer- induced model of pulmonary injury successfully identified specific endpoints of injury. This model was used to study the protein profiles in response to polymer-induced lung injury. 2D SDS PAGE was optimised for use with BAL fluid and identified two interesting proteins, prosaposin and calgranulin A, which have the potential to act as biomarkers for lung injury. Furthermore, immunohistochemistry can provide an insight into co-localization and quantitative analysis of proteins identified by proteomics with cellular organisation/structure, which in turn, may be reflective of their function. This was demonstrated using two proteins, cocoacrisp and surfactant protein A that were found to have elevated levels in tissue sections from the polymer treated lungs. Finally, in addition to all these proteins being potential biomarkers of lung injury, they are also prospective targets for clinical treatment.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
ISBN:	9781303204111
Funders:	Unilever, BBSRC
Date of First Compliant Deposit:	30 March 2016
Last Modified:	10 Aug 2024 10:54
URI:	https://orca.cardiff.ac.uk/id/eprint/56036

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