Human and rodent decay-accelerating factors (CD55) are not species restricted in their complement-inhibiting activities

Homologous complement activation is restricted on cells by the complement r egulators, decay-accelerating factor (DAF), membrane cofactor protein (MCP) and CD59. These proteins act in concert with other membrane structures to protect cells from homologous complement attack. In contrast, cells are usu ally sensitive to heterologous complement attack. It has been suggested tha t species-specific restriction of complement activation can be attributed t o the inability of regulators to inhibit across species. We have investigat ed the capacities of human, rat and mouse analogues of DAF to regulate homo logous and heterologous complement. Cells transfected with cDNA encoding th ese analogues were protected from heterologous complement attack. C3b-depos ition experiments indicated that whilst cells were best protected by DAF fr om the same species, ail three analogues inhibited human, rat and mouse com plement. Comparable results were obtained in haemolysis assays using solubl e, recombinant forms of the proteins. Inhibition of the classical pathway ( CP) was best achieved with homologous DAF, although human DAF also inhibite d rat complement, rat DAF also inhibited human complement and mouse DAF inh ibited complement from all species. Human DAF was the best inhibitor of alt ernative pathway (AP)-mediated attack, inhibiting complement from all speci es. Mouse DBF inhibited mouse and rat AP, whilst rat DAF inhibited only rat AP. These data indicate that human and rodent analogues of DAF are not spe cies restricted and highlights interesting differences in the capacity to r egulate AP and CP. This has implications in broader fields of research, suc h as xenotransplantation, where cross-species regulation of complement is o f paramount importance.