The role of lipid laden macrophages in airways disease

Hayman, Yvette A.

Medicine
September 2012

Thesis or dissertation


Rights
© 2012 Yvette Arabella Hayman. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

Asthma is a chronic inflammatory disease of the airway and is often associated with Gastro-Oesophageal Reflux (GOR). Lipid laden macrophages (LLM) in the airway have previously been reported indicative of aspiration secondary to GOR. We hypothesised that lipid droplets from undigested or partially digested food may be aspirated into the airway and accumulate in scavenging macrophages thus generating an activated population that interact with other immune cells to induce an asthma-like state of disease.

Using a lipid laden alveolar macrophage index, we collected 29 bronchoalveolar
lavage (BAL) samples from patients with a variety of respiratory disorders, to
determine the use of this test in GOR diagnosis. We investigated the mode of uptake of unmodified lipid and other alternative sources of lipid. We attempted to generate polarised activated macrophages and to determine the activation status of LLM. We also characterised a new macrophage cell line, and compared these to PMA differentiated THP-1 macrophages.

We have shown that the LLAMI is incapable of diagnosing GOR. We showed that macrophages are capable of direct dietary lipid uptake, independently of actin or CD36. Lipid accumulation also results from the phagocytic clearance of apoptotic epithelial cells, which may account for the lack of LLAMI specificity for GOR. Our attempts to generate and distinguish polarised macrophages were unsuccessful and as a result, we were not able to determine the activation status of LLM. We demonstrated heterogeneity among primary macrophage cells isolated from BAL fluid collected from patients with varying pathologies. Particularly interesting was the finding that macrophages isolated from a patient with GOR showed distinctly greater CD36 expression. Daisy cells are novel cells which appear to be macrophage-like morphologically, functionally and phenotypically. Daisy cells have potential utility with the ability to spontaneously replicate and differentiate an advantage over THP-1 cells which require PMA stimulation.

Publisher
Postgraduate Medical Institute, The University of Hull
Supervisor
Morice, Alyn H.; Hart, Simon P.
Qualification level
Doctoral
Qualification name
PhD
Language
English
Extent
5 MB
Identifier
hull:8014
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