Date of Award

2017

Document Type

Master Thesis

Degree Name

Masters of Science (Research)

Department

Biological & Pharmaceutical Sciences

First Advisor

Dr. Joanna B. Tierney

Abstract

Inflammation is a natural protective response and is characterised by the activation of numerous immune cells, including macrophages which can release a variety of inflammatory mediators. Macrophages play a flexible role in the initiation and effector phases of the immune response and change their behaviour to respond to environmental stimuli. The main objectives in this study were to create and characterise different macrophage behaviours and employ a novel metabolic characterisation platform the Phenotype MicroarrayTM to attribute additional characteristics to the currently well recognised phenotypes. Five activated macrophage states were demonstrated and characterised. Unactivated macrophages (MO) demonstrated undetectable levels of NO, IL-12 and 11-10 production. A classic activated state (Ml) was created by inducing with IFN-y and LPS which resulted in elevated levels IL-12, NO and low levels of IL-10. Elevated expression of cell surface markers including CD86, MCP-1 and CD 150 SLAM was detected. The alternative activated state (M2) was induced with the antiinflammatory cytokine IL-4 and resulted in low IL-12 and NO and elevated IL-10 with high levels of expression of cell surface markers of CD86, MCP-, I-Ab, CD40 and SLAM. An alternative hybrid activated state created by stimulation with lL-4 and LPS showed high levels of IL-10, low levels of NO and IL-12 and elevated expression of CD40, CD86 and CD150. A regulatory activated state (M4) was prompted by Fey receptor ligating complexes of SRBC-IgG and stimulation with LPS. High production levels of IL-10 and NO with decreased levels of IL-12 evident. Elevated expression of CD40, CD80, CD86 and CD150 SLAM was observed. The metabolic response of activated macrophage cell states to substrates on the Phenotype MicroarrayTM is described.

Access Level

info:eu-repo/semantics/openAccess

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Bacteriology Commons

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