The role of lipid laden macrophages in airways disease

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 bronchoalveolarlavage (BAL) samples from patients with a variety of respiratory disorders, todetermine 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.

Name dc:type.qualificationname

PhD

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Hull

Year dc:date.issued

2012

Author dc:creator

• Hayman, Yvette A.

Advisors dc:contributor.advisor

• Morice, Alyn H.
• Hart, Simon P.

• Medicine

Language dc:language

en

Identifier

oai:hull-repository.worktribe.com:4214940

OAI identifier oai:identifier

oai:hull-repository.worktribe.com:4214940