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Title: The role of tetraspanins in neutrophil survival and phagocytosis
Author: Ciuntu, Andreea
ISNI:       0000 0004 6421 9204
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2017
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Inflammation is a beneficial process in the body that involves immune cell migration in the tissue in response to injury or infection. Failure to resolve inflammation is seen in chronic inflammatory diseases, such as Chronic Obstructive Pulmonary Disease (COPD). Neutrophils are at the very centre of this process, where they persist in the tissue due to ongoing recruitment and delayed apoptosis. Furthermore, failure to phagocytose and kill important clinical pathogens such as the multi-antibiotic resistant Staphylococcus aureus, compounds the pathogenesis of inflammatory disease and patients succumb to life-threatening infections. The aim of this thesis was to determine whether tetraspanins, a family of transmembrane receptors that play roles in cell survival and immune functions, are involved in neutrophil lifespan and phagocytosis. Primary human neutrophils were isolated from the blood of healthy subjects and COPD patients. Anti-CD63 antibodies and Fab fragments delayed constitutive neutrophil apoptosis of both healthy and COPD neutrophils as indicated by morphology and AnnexinV staining. Donors varied in their responsiveness to anti-CD63 antibodies. All subjects expressed CD63 and survival rates did not correlate with CD63 regulation. Anti-CD151 antibodies significantly reduced neutrophil phagocytosis of heat killed and live S. aureus but not S. pneumoniae or H. influenzae. Gentamicin protection assays confirmed that anti-CD151 antibodies reduced the number of intracellular viable S. aureus. Fluorescent microscopy showed that anti-CD151 antibodies reduced the numbers of pHrodo stained S. aureus present in the acidified phagosome. The data presents novel and potential roles for tetraspanins in pathways underpinning neutrophil survival and interaction with S. aureus. Our findings suggest that CD63 may play a role in neutrophil survival while CD151 may play a key role in neutrophil interaction with S. aureus. The study provides two potential molecular targets for modulating neutrophil lifespan and S. aureus neutrophil interactions.
Supervisor: Prince, L. R. ; Partridge, L. J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available