Figure 10.

Schematic for Factor H (FH)-mediated control of complement at the platelet/granulocyte interface. (A) Wild-type (WT) FH negatively regulates complement activation and platelet/granulocyte aggregate (PGA) formation. (B) The rH19–20 fragment that is used in the in vitro assays competitively inhibits the ability of full-length FH to regulate complement activation, resulting in increased C5a generation, CR3 expression, and thus increased PGA formation. (C) The rH19–20 mutants used in the assays have variable ability to inhibit full-length FH-mediated complement regulation. Compared to WT rH19–20, the mutants may bind poorly to cells and have less impact on full-length FH-mediated protection from complement, resulting in reduced complement activation and PGA formation. If the rH19–20 mutant is not affected in his ability to bind, it will effectively compete with full-length FH, similar to WT rH19–20 (depicted in B), leading to increased complement activation and PGA formation. (D) Atypical hemolytic uremic syndrome-associated mutations in the C-terminus of full-length FH may have variable ability to bind to cells and will thus result in similar or increased PLA formation as compared to WT FH. Dotted lines represent variable effect on complement activation on cell surfaces or variable ability to bind/compete.