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Title: Macrophage subpopulations in COPD
Author: Dewhurst, Jennifer
ISNI:       0000 0004 5364 1979
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2015
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Lung macrophage numbers are increased in Chronic Obstructive Pulmonary Disease (COPD). Macrophage subpopulations with differences in cell surface marker expression and function have been identified in sputum. The aim of this thesis was to investigate the role of lower airway macrophage subpopulations in COPD, focussing on their phenotype and function. Alveolar and interstitial cells from human lung resection tissue were isolated by perfusing the airways with saline. Interstitial cells were isolated by mechanically and enzymatically digesting perfused lung tissue. Alveolar and interstitial macrophages were negatively selected using a monocyte enrichment kit. Flow cytometry and PCR were used to identify and phenotype macrophage subpopulations. A flow cytometry based phagocytosis assay was used to characterise the function of macrophage subpopulations. Subpopulations of alveolar macrophages and interstitial macrophages were identified as “small macrophages” and “large macrophages” based on size and granularity. Small macrophages were further characterised as HLA-DRhigh, CD14high, CD38high, CD36high, CD206low. Large macrophages were characterised as HLA-DRlow, CD14low, CD38low, CD36low, CD206high. The percentage of large macrophages was reduced in the interstitium compared to alveolar macrophages, while the opposite pattern was observed for small macrophages (increased percentage in interstitium). No significant differences between the proportion of macrophage subpopulation from COPD patients and smokers have been observed. Large interstitial macrophages were 66% apoptotic. Small interstitial macrophages had high inflammatory potential but low phagocytic ability; small alveolar macrophages had intermediate inflammatory potential but high phagocytic ability; large alveolar macrophages had low inflammatory potential and low phagocytic ability. In addition the phenotype and function of large macrophages from COPD patients was sensitive to current smoking. I have shown phenotypically different subpopulations of alveolar and interstitial macrophages exist. The proportion of small and large macrophages varies between the interstitium and alveolar space. Small macrophages appear to polarised towards an inflammatory phenotype compared to large macrophages. Therefore targeting macrophages for COPD therapy should be tailored towards specific subpopulations.
Supervisor: Not available Sponsor: Novartis Institutes for BioMedical Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available