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Title: Calprotectin in the host response to infection
Author: Clohessy, Paul
ISNI:       0000 0001 3559 1697
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1996
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The S100 zinc-binding protein, calprotectin, is a noncovalently associated anionic complex which incorporates two immunologically distinct polypeptides in a molecule of Mr 36.5 kDa. Calprotectin's abundance in neutrophils, where it constitutes 60% of cytosolic protein, suggests an innate host defence function. In vitroit is microbiostatic. The trace metals, iron and zinc, are essential to the growth of most microorganisms. During the acute phase response to infection in man, the marked decrease in plasma iron is associated with a reduction in microbial growth. The similar, though smaller decrease in plasma zinc during this response to infection, may also act as a protective measure. As most microorganisms appear not to have zinc retrieval agents analogous to siderophores for iron retrieval, pathogenic microorganisms may be more susceptible to zinc deprivation than to iron deprivation. Thus, we hypothesized that calprotectin's in vitro candidastatic activity may be mediated by zinc chelation and that this phenomenon may also occur, in vivo, in plasma. In Sabouraud's culture medium, we demonstrated that calprotectin, at concentrations as low as 10ml, has potent, pH dependent candidastatic activity associated with zinc chelation. In plasma from children with cystic fibrosis (CF) & infected children, we demonstrated increased plasma calprotectin concentrations (median: 1832 & 4753 g/l respectively) compared to controls (median: 685 g/l). Plasma calprotectin concentration correlated positively with serum C- reactive protein in infected children, reflecting an association with the acute phase response. In CF children, there were positive correlations between plasma calprotectin and plasma copper and between plasma calprotectin and the Northern score, reflecting associations with the acute phase response and the extent of lung involvement respectively.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Cystic fibrosis