Naturally occurring anti-band-3 antibodies and complement together mediate phagocytosis of oxidatively stressed human erythrocytes.
Treatment of erythrocytes with the thiol-specific oxidant azodicarboxylic acid bis(dimethylamide) (diamide) enhances their phagocytosis by adherent monocytes. Phagocytosis of diamide-treated erythrocytes required that the cells were opsonized with whole serum, since complement inactivation abolished phagocytosis. Opsonization with whole serum containing 20-100 times the physiological concentration of naturally occurring anti-band-3 antibodies enhanced phagocytosis of diamide-treated erythrocytes. High inputs of anti-band-3 also restored phagocytosis of erythrocytes that had been incubated with complement-inactivated serum. Elevated concentrations of anti-spectrin antibodies were ineffective in whole and complement-inactivated serum. Specific recognition of diamide-treated erythrocytes by anti-band-3 antibodies may be due to generation of anti-band-3 reactive protein oligomers on intact diamide-treated erythrocytes. Generation of such oligomers was dose-dependent with respect to diamide. Bound anti-band-3 alone was not sufficient to mediate phagocytosis. It resulted in deposition of complement component C3b on the cells through activation of the alternative complement pathway in amounts exceeding that of bound antibodies by two orders of magnitude. Thus, anti-band-3 and complement together mediate phagocytosis of oxidatively stressed erythrocytes, which stimulate senescent erythrocytes with respect to bound antibody and complement.
Lutz
H U
HU
Department of Biochemistry, Swiss Federal Institute of Technology, Zurich.
Bussolino
F
F
Flepp
R
R
Fasler
S
S
Stammler
P
P
Kazatchkine
M D
MD
Arese
P
P
D001457:Anion Exchange Protein 1, Erythrocyte / Q000276:immunology / Q000502:physiology*; D000906:Antibodies; D000936:Antigen-Antibody Complex; D003179:Complement C3b / Q000378:metabolism*; D003958:Diamide / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D016177:Macrophage-1 Antigen; D010587:Phagocytosis; D011951:Receptors, Complement / Q000378:metabolism*
D001457:Anion Exchange Protein 1, Erythrocyte; D000906:Antibodies; D000936:Antigen-Antibody Complex; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D003958:Diamide; D003179:Complement C3b