title: The C-terminus of complement factor H is essential for host cell protection.
abstract: Complement is a powerful self-amplifying system of innate immune defense with the capacity to eliminate microbes directly. Factor H is a central regulator in plasma which protects host tissue from complement mediated damage. Here we characterize the relevance of surface attached factor H, and study the regulatory activity of factor H on endothelial cells. Although these cells expressed membrane bound regulators, cell bound factor H contributed substantially to complement regulatory activity at the cell surface. Blockade of the C-terminus of factor H with monoclonal antibodies inhibited cell binding of this soluble regulator and resulted in enhanced complement activation on the cells. In the absence of factor H, increased deposition and slower inactivation of C3b resulted in higher amount of membrane attack complexes on the cell surface. When the membrane regulators CD55 and CD59 were removed by enzymatic treatment, complement mediated cell lysis was enhanced in the absence of factor H. Importantly, inhibition of the C-terminus did not compromise the regulatory function of factor H in fluid phase. Altogether these data point to a highly relevant, yet so far underestimated role of factor H for complement control at cellular surfaces, and reveal a decisive role of the factor H C-terminus in host cell recognition and protection.
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Beutenbergstrasse 11a, D-07745 Jena, Germany. Mihaly.Jozsi@hki-jena.de
authors.forename: Mihály
authors.initials: M
authors.lastname: Józsi
authors.forename: Martin
authors.initials: M
authors.lastname: Oppermann
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018958:CD55 Antigens / Q000032:analysis; D018957:CD59 Antigens / Q000032:analysis; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology; D003179:Complement C3b / Q000032:analysis / Q000378:metabolism; D017242:Complement Factor H / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology*; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D051916:Membrane Cofactor Protein / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; D018958:CD55 Antigens; D018957:CD59 Antigens; D051916:Membrane Cofactor Protein; D003179:Complement C3b; D017242:Complement Factor H