Different Epitopes of the Macrophage Type Three Complement Receptor (CR3) Are Used to Bind Leishmania Promastigotes Harvested at Different Phases of Their Growth Cycle
A number of studies1–4 have demonstrated that monoclonal antibodies (MAbs) directed against the type three complement receptor (CR3) block the binding and ingestion of Leishmania promastigotes by host macrophages. This receptor is known to recognise the inactivated form of complement factor 3 (iC3b)5 and to mediate direct leetin-like attachment of particles such as yeast zymosan. Binding via these different sites on CR3 may have important implications for parasite survival since ligation via the leetin-binding site stimulates release of antimicrobial reactive oxygen intermediates whereas ligation of iC3b does not6. In our earlier studies1 we had demonstrated that the anti-CR3 MAb M1/70, Fab-anti-C3, and the nucleophile sodium salicyl hydroxamate (Sana), which inhibits the covalent binding of C3 to an activator surface, all inhibited the serum-independent uptake of L. donovani promastigotes to equivalent degrees. This suggested that binding of promastigotes to CR3 was complement mediated, and was supported by our subsequent demonstration of Saha-inhibitable deposition of macrophage derived C3 on the promastigote surface7.
KeywordsGrowth Cycle Complement Receptor Late Stationary Phase Host Macrophage Footpad Thickness
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