Characterization of the enhanced susceptibility of paroxysmal nocturnal hemoglobinuria erythrocytes to complement-mediated hemolysis initiated by cobra venom factor.
When whole serum C is activated by cobra venom factor complexes (CoFBb), paroxysmal nocturnal hemoglobinuria (PNH) III E (the most C-sensitive type) are hemolyzed, but normal and PNH II E (the intermediately sensitive type) are not. Previous studies have shown that after exposure to CoFBb and serum, PNH III E bind relatively large amounts of the trimolecular C complex, C5b67, whereas normal and PNH II E bind virtually none. In the studies reported herein, we have observed that when normal and PNH III E are incubated with isolated C5, C6, and 125I-C7 in the presence CoFBb, the normal E bind more C5b-7 than the PNH cells. When C7-deficient serum is included in the reaction mixture, however, the PNH E are once again observed to bind much greater amounts of C5b-7. These observations suggest that plasma and membrane factors act in concert to restrict the assembly of the trimolecular C5b-7 complex on human E. PNH III E appear to be deficient in the membrane component of this inhibitory system.
Parker
C J
CJ
Department of Medicine, University of Utah Medical Center, Salt Lake City.
Stone
O L
OL
Bernshaw
N J
NJ
D000818:Animals; D003167:Complement Activation; D003179:Complement C3b / Q000502:physiology; D003184:Complement C7 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology; D004546:Elapid Venoms / Q000378:metabolism / Q000494:pharmacology*; D004912:Erythrocytes / Q000378:metabolism; D006168:Guinea Pigs; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood*; D006461:Hemolysis; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D011817:Rabbits; D011951:Receptors, Complement / Q000032:analysis
D003184:Complement C7; D015938:Complement Membrane Attack Complex; D004546:Elapid Venoms; D007074:Immunoglobulin G; D011951:Receptors, Complement; C016310:cobra venom factor; D003179:Complement C3b; C050974:complement C5b-6 complex; D003165:Complement System Proteins