The complement system (C) present in circulating blood is an effective mechanism
of host defense, responsible for the killing of pathogens and the production of potent
anaphylatoxins. Inhibitors of the C have been described in the saliva of hematophagous
arthropods that are involved in the protection of digestive tissues against C-mediated
damage. Here we describe albicin, a novel inhibitor of the alternative pathway of
complement from the salivary glands of the malaria vector, Anopheles
albimanus. The inhibitor was purified from salivary gland homogenates by
reverse phase HPLC, and identified by mass spectrometry as a small (13.4 kDa) protein
related to the gSG7 protein of An. gambiae and An.
stephensi. Recombinant albicin was produced in Escherichia
coli and found to potently inhibit lysis of rabbit erythrocytes in assays of
the alternative pathway while having no inhibitory effect on the classical or lectin
pathways. Albicin also inhibited the deposition of complement components on agarose-coated
plates, although it could not remove previously bound components. Antisera produced
against recombinant albicin recognized both the native and recombinant inhibitors and also
blocked their activities in in vitro assays. Using surface plasmon
resonance and enzymatic assays, we found that albicin binds and stabilizes the
C3-convertase complex (C3bBb) formed on a properdin surface, and inhibits the convertase
activity of a reconstituted C3bBb complex in solution. The data indicate that albicin
specifically recognizes the activated form of the complex allowing more efficient
inhibition by an inhibitor whose quantity is limited.