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Title: Characterisation and functional significance of the interaction between myeloperoxidase and caeruloplasmin
Author: Griffin, S.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1999
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The acute phase protein caeruloplasmin consistently co-purified with circulating anti-MPO antibodies when plasma from both patients and healthy controls underwent affinity chromatography over either native or recombinant human MPO. Caeruloplasmin inhibited MPO enzymatic activity in both a dose- and time-dependent manner, suggesting an in vivo role as a physiological inhibitor of MPO. Affinity-purified anti-MPO antibodies from patients with active renal vasculitis inhibited the binding between MPO and caeruloplasmin, correlating with a reversal of the caeruloplasmin-mediated inhibition of MPO activity. The affinity of the interaction between MPO and anti-MPO antibodies was shown to be higher than that between MPO and caeruloplasmin, indicating that binding to the autoantibody would be favoured in vivo. Studies using patient sera confirmed preferential binding of MPO to anti-MPO antibodies compared to caeruloplasmin. Compared to healthy controls and patients with active anti-MPO vasculitis, free MPO and MPO-caeruloplasmin complexes were found to be elevated in the sera of patients with an acute inflammatory response, whereas MPO-ANCA complexes were elevated only in the patients with vasculitis. There was a trend for lower relative caeruloplasmin activity in the patients with vasculitis. The results contribute to current understanding of the mechanism of inhibition of MPO activity in neutrophil-mediated inflammation, and how this might be disturbed in the presence of anti-MPO antibodies. The reduction in hydrogen peroxide-mediated cell permeabilisation in the presence of MPO suggests that the mechanism of action of MPO in host inflammation is other than by an immediate increase in cell death.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available