Factor H mediated cell surface protection from complement is critical for the survival of PNH erythrocytes.
Paroxysmal nocturnal hemoglobinuria (PNH) cells are partially (type II) or completely (type III) deficient in GPI-linked complement regulatory proteins CD59 and CD55. PNH III erythrocytes circulate 6 to 60 days in vivo. Why these cells are not lysed as rapidly by complement as unprotected foreign cells, which normally lyse within minutes, remains undetermined. Factor H plays a key role in the homeostasis of complement in fluid phase and on cell surfaces. We have recently shown that a recombinant protein encompassing the C-terminus of factor H (rH19-20) specifically blocks cell-surface complement regulatory functions of factor H without affecting fluid-phase control of complement. Here we show that PNH II and III cells become highly susceptible to complement-mediated lysis by nonacidified normal human serum in vitro, when the cell surface complement-regulatory functions of factor H are blocked. The results indicate that cells deficient in surface-bound regulators are protected for extended periods of time by factor H.
Ferreira
Viviana P
VP
Department of Biochemistry, Center for Biomedical Research, University of Texas Health Science Center, Tyler, TX 75708, USA. viviana.ferrreira@uthct.edu
Pangburn
Michael K
MK
D000328:Adult; D001798:Blood Proteins / Q000502:physiology*; D018958:CD55 Antigens / Q000378:metabolism; D018957:CD59 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D002470:Cell Survival; D017242:Complement Factor H / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003165:Complement System Proteins / Q000378:metabolism*; D004905:Erythrocyte Aging; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000502:physiology*; D005434:Flow Cytometry; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood*; D006461:Hemolysis; D006801:Humans
D001798:Blood Proteins; D018958:CD55 Antigens; D018957:CD59 Antigens; D017242:Complement Factor H; D003165:Complement System Proteins