Submitted April 6, 2007
Accepted June 1, 2007
Factor H-mediated cell surface protection from complement is critical for the survival of PNH erythrocytes
Viviana P Ferreira* and Michael K Pangburn
Dept of Biochemistry, Center for Biomedical Research, University of Texas Health Science Center, Tyler, TX, United States
* Corresponding author; email: viviana.ferreira{at}uthct.edu.
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 6-60 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 non-acidified 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.
