Mapping the inflammatory process in neonatal lung disease

Maxwell, Nicola Claire 2010. Mapping the inflammatory process in neonatal lung disease. PhD Thesis, Cardiff University.

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Abstract

Chronic lung disease (CLD) of prematurity is a significant complication of preterm birth in which the neutrophil appears to be the key cell of inflammation. Lack of resolution of neutrophilic inflammation, due to delayed or dysregulated neutrophil apoptosis, is thought to be an important component of the pathogenesis of CLD. In this thesis, I sought to examine the inflammatory process in the lungs of ventilated newborn infants. I have established a reliable method for the use of flow cytometry, a technique not previously reported in the study of neonatal bronchoalveolar lavage (BAL) samples, and have described both the cellular and supernatant components of BAL from term and preterm infants, paying particular attention to the role of infection. I found higher peak neutrophil counts in infants developing CLD, as well as more immature, monocyte-like, macrophages and higher rates of detection of microbial DNA when compared to term infants and infants whose respiratory distress syndrome resolved. I focused more specifically on the role of neutrophil apoptosis in CLD and sought to understand the mechanism for the delay in neutrophil apoptosis in newborn infants and how this may impact on lung disease. BAL supernatants from term infants showed more pro-apoptotic activity against adult neutrophils than BAL from preterm infants. I found a delay in apoptosis in lung neutrophils in preterm infants and confirmed this delay in blood neutrophils of term infants compared to adults. I have shown that this delay might be due to differential expression of anti-apoptotic proteins Bcl-xl and Mcl-1 between cord and adult neutrophils, which has not previously been described.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
ISBN:	9781303195426
Date of First Compliant Deposit:	30 March 2016
Last Modified:	19 Mar 2016 23:29
URI:	https://orca.cardiff.ac.uk/id/eprint/54354

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