C-reactive protein (CRP) is a member of the pentraxin family which opsonises S. pneumoniae through its binding to phosphorylcholine. In addition, CRP binds to Fcγ receptors: FcγRI with high affinity and, probably, FcγRIIA with lower affinity. Binding to FcγRIIA was suggested to depend on a polymorphism at residue 131 of the receptor, HH individuals being poorer binders compared to RR. To clarify the role of CRP binding to FcγRIIA and functional activities upon interaction, neutrophils from HH and RR individuals were incubated with CRP in the presence or absence of pneumococci type 3. No difference in activation as determined by IL-8 synthesis, respiratory burst and phagocytosis were seen between HH and RR donors. Since CRP increases its serum concentration up to 1000 fold above the normal level, we also compared acute-phase concentrations of CRP with normal levels for neutrophil functions. Normal (≤10 μg/ml) and acute-phase (10 - 100 μg/ml) levels increased IL-8 production in the presence or absence of pneumococci. A similar pattern was seen for extracellular reactive oxygen. There was a five-fold increase in DHR oxidation in neutrophils when CRP at 10 μg/ml was used, although this was reduced when CRP at 50 and 100 μg/ml was used in both HH and RR donors. Recombinant CRP also gave a similar pattern in which higher MFIs for DHR oxidation were obtained for CRP at 10 μg/ml. On average a two-fold increase in phagocytosis of pneumococci serotype 3 was obtained for both type of donors for CRP at 10 μg/ml. This effect was also reduced at acute-phase levels of CRP. The down-regulatory effects of CRP are thus selective for certain responses but do not require phagocytosis since CRP at 50 - 100 μg/ml could also inhibit PMA activation. The ability of CRP to bind to Fcγ-receptors using surface plasmon resonance was evaluated, but there was no evidence of CRP binding to FcγRIIA, RIIB or RIII Serum amyloid P component showed strong binding to FcγRIII and weak binding to FcγRIIA and RIIB. A glycosylated form of the Fc receptor may be required for binding
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:406710 |
| Date | January 2004 |
| Creators | Rodriguez, Jairo Antonio |
| Publisher | London School of Hygiene and Tropical Medicine (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://researchonline.lshtm.ac.uk/682313/ |
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