Modulation of classical C3 convertase of complement by tear lactoferrin.

Lactoferrin isolated fom normal human tears was shown to inhibit the complement-mediated lysis of antibody-coated red cells. The anti-complementary effect of lactoferrin on serum complement could be reversed by adding Fe3+ but not by Mg++ or Ca++. Lactoferrin did not inhibit the formation of EAC14 but markedly blocked the assembly of the EAC142 enzyme. Once the C3 convertase was formed lactoferrin did not affect the function of the enzyme and only had a minor effect on the intrinsic decay of C2 from the convertase. Inhibition of the C3 convertase formation was not seen by preincubating EAC14 intermediates with lactoferrin, but only occurred when lactoferrin and C2 were incubated together with EAC14 cells. Our findings suggest that lactoferrin may play an anti-inflammatory role by modulating activation of the complement system.