This project has focused on the interaction of <I>B. cepacia</I> with neutrophils, the predominant immune cell in CF. As <I>B. cepacia</I> is resistant to neutrophil non-oxidative killing mechanisms, respiratory burst induction by <I>B. cepacia</I> was investigated using another CF pathogen, <I>Pseudomonas aeruginosa,</I> as a comparison. In general, non-opsonised CF isolates of <I>B. cepacia</I> induced little respiratory burst activity. By contrast, <I>P. aeruginosa</I> strains induced a greater range of responses, with a subset of strains inducing considerable activity. Opsonisation with specific immune sera increased neutrophil responses to both <I>B. cepacia</I> and <I>P. aeruginosa</I>. However, in view of the cleavage of opsonins and opsonin receptors within the CF lung, opsonisation may have little impact on host defences to <I>B. cepacia</I> within the respiratory tract. Lipopolysaccharide (LPS) extracted from <I>B. cepacia</I> was shown to upregulate neutrophil expression of complement receptor 3 (CR3) and to prime respiratory burst responses to fMet-Leu-Phe and to whole bacteria. Significantly LPS from the major epidemic strain of <I>B. cepacia, </I>ET12, increased neutrophil respiratory burst responses to <I>P. aeruginosa</I> but not to the ET12 strain itself. Thus it was speculated that <I>B. cepacia</I> may establish a foothold in the <I>P. aeruginosa</I>-infected lung by selectively upregulating immune responses to <I>P. aeruginosa</I>. In view of the development of environmental <I>B. cepacia</I> as biocontrol agents, environmental and clinical isolates were compared for potential virulence determinants. Few obvious differences were found between CF, non-CF clinical and environmental strains. Significantly LPS from two environmental strains of <I>B. cepacia </I>primed neutrophil responses to a similar degree as LPS from CF strains of <I>B. cepacia</I>. A surprising result was that an environmental <I>B. cepacia</I> strain was less effectively cleared in both CF and non-CF mice than the ET12 strain. This project has provided evidence to support the hypothesis that <I>B. cepacia</I> colonisation is associated with a marked and damaging immune response in CF patients.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:652696 |
| Date | January 1998 |
| Creators | Hughes, Jayne |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/21310 |
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