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Title: Studies on alpha2-macroglobulin and cytokine interactions
Author: Elliott, Sarah-Francess
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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The aim of the present study was to establish if α2M bound a number of previously unstudied cytokines of immunological importance, and if so, did this influence their immuno- and bio-reactivity. It was apparent that IL2, TNFα and IFNγ bound to α2M. For all three cytokines the binding was stronger with α2M-methylamine (α2Mm), a chemically altered form of α2M that has a physiological equivalent. Subsequent biochemical studies were carried out using α2Mm. To analyse the quantitative interaction of cytokines with α2Mm, a novel radioimmunoassay system was developed using anti-human α2M polyclonal reagent as the capture antibody. In addition, the zinc affinity Sephacryl system that had been used in earlier qualitative studies was adapted to a tube system to permit batch analysis of α2Mm-cytokine interactions. These techniques revealed a binding affinity for IL2 with α2Mm of kd = 2.1-2.5 x 10-5M, while that of TNFα with α2Mm was Kd = 0.97-1.35 x 10-5M. Furthermore, IL2 bound non-specifically whereas TNFα showed a specific interaction with the serum protein. The relevance of such interactions was studied by determining the effect of α2M on commercial cytokine immunoassays. It was found that α2M and its derivatives may mask or enhance the detection of a number of cytokines, the effect being dependent on the cytokine and on the source of the kit. The influence of α2Mm on the bioactivity of IL2 and TNFα was examined in lymphoproliferative and antiproliferative assays respectively. These studies revealed that the complexing of TNFα with α2Mm ablated its bioactivity, whilst that of IL2 was maintained when complexed with the protein. In conclusion, the results presented corroborate previous work in the literature and extend our knowledge of α2M-cytokine interactions and its effects.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available