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Expression of a1-Adrenergic receptors on immune cells during inflammation

Nguyen, Harry (2015) Expression of a1-Adrenergic receptors on immune cells during inflammation. Honours thesis, Murdoch University.

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The immune system is a complex network of interacting cells and proteins that are constantly protecting the host from pathogens. Lymphoid and myeloid cells are the cellular mediators of the immune system, and the functions of these cells are partly controlled by the nervous system, however the mechanisms are not understood. The sympathetic nervous system may play a role through a family of receptors called adrenergic receptors (AR). Adrenergic receptors are G-protein coupled receptors that mediate the actions of adrenaline and noradrenaline. These receptors are spilt into the a- and b- subtypes, which can be further divided into subtypes. While b-ARs have been well-studied, less is known about a-ARs and their roles in immune regulation. The a-ARs can be divided into the a1- and a2 - subtypes: this project focussed on the a1-ARs as there is evidence to suggest that they play a role in inflammatory diseases. However, relatively little is known about which immune cell types express a1-ARs, and how they vary during inflammation.

The major Aim of this project was to examine the expression of a1-ARs on lymphoid and myeloid cells in mouse spleen and establish whether simulating an acute inflammatory response (bacterial lipopolysaccharide: LPS) in splenocytes would alter the protein expression of a1-ARs. Protocols were optimised for the multi-parameter labelling and analysis of mouse spleen lymphoid and myeloid cells by flow cytometry, and the optimisation of specific a1-AR surface protein staining using BODIPY-prazosin. Normal mouse lymphoid and myeloid populations were found to express varying levels of -ARs, and that all except plasmacytoid dendritic cells (pDC) showed an unexpected reduction in a1-AR protein expression after exposure to LPS in vitro. The results of this project provide preliminary evidence that except for pDC, lymphoid and myeloid cell populations within the spleen undergo downregulation of a1 -ARs during an acute inflammatory response.

Publication Type: Thesis (Honours)
Murdoch Affiliation: School of Veterinary and Life Sciences
Supervisor: Drummond, Peter and Stumbles, Phil
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