Comparison of surface recognition and C3b binding properties of mouse and human complement factor H

Factor H (FH) is a central complement regulator both in plasma and on certain cellular and acellular surfaces that are in contact with plasma. Although FH deficiency has been shown to lead to similar diseases in man and mice (membranoproliferative glomerulonephritis or dense deposit disease) little is known about the similarity between the human and murine FH functions. We here characterize the interactions of murine FH (mFH) with C3b, glycosaminoglycans, and endothelial cells and compare these interactions with those of human FH (hFH). To achieve this we purified mFH and murine 0 from plasma, prepared murine Ob, and expressed recombinant mFH constructs containing domains 1-5 and 18-20 (mFH1-5 and mFH18-20). For comparisons, hFH, human Ob, and recombinant hFH1-5 and hFH18-20 were used. We demonstrate that mFH and mFH 1-5 do act as cofactors for factor I-mediated cleavage of human Ob. Surface plasmon resonance analysis showed binding of mFH 18-20 to murine Ob and weak binding to human Ob. The mFH 18-20 construct bound to heparin in a manner comparable to hFH 18-20. It was demonstrated by flow cytometry that mFH and mFH 18-20 bind to human endothelial cells in a similar manner to hFH and hFH 18-20. Taken together, locations of the key functions of mFH, i.e. complement regulation and surface recognition, are comparable to hFH. Recently, mutations in the carboxy-terminal end of hFH have been found to be associated with atypical hemolytic uremic syndrome (aHUS). Based on the results in this report it is conceptually attractive to establish a murine model for aHUS. (C) 2005 Elsevier Ltd. All rights reserved.