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Title: Characterisation of a cell-surface marker of apoptosis
Author: Chong Goh, Yaw
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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The studies undertaken in this research project characterised as fully as possible the antigen identified by the monoclonal antibody BOB78. Earlier studies have linked BOB78 to the identification of apoptotic cells. The present project extended this finding by further studies utilising various antibody-based techniques on cancer-derived cell lines in different stages of apoptosis. The BOB78 antigen was confirmed to be present in normal blood cells and to be multi-lineage. BOB78 is normally expressed within the cytosol of nucleated blood cells, but absent in anucleated red blood cells which do not undergo apoptosis. BOB78 was found to be present in platelets as they develop from the membranes of the MEG-01 megakaryocytes by flow cytometric analysis. BOB78 was also expressed on the surface of senescent platelets. These MEG-01 platelets were therefore used for purification of BOB78 through immunoprecipitation. The captured BOB78 antigen was sequenced through MALDI-TOF, which identified it as chaperonin, also known as heat shock protein 60 (hsp60). Platelets are equipped with caspases and when senescent display membrane changes typical of apoptotic cells. Like apoptotic cells, platelets are normally cleared from tissues by macrophages. Surface expression of hsp60 is probably an essential change marking cellular entities for uptake by phagocytes. It remains to be studied if engulfment of bodies displaying an endogenous moiety like hsp60 might play a key role in mediating a non-inflammatory response observed in apoptosis. It may also be speculated that hsp60 serves the function of molecular mimicry as many intracellular bacteria display surface hsp60, the expression of which has been linked to pathogenic invasiveness. The ability of these microbes to evade immune clearance may be linked to the non-inflammatory apoptotic disguise which surface hsp60 confers on them.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available