Analysis of the effects of activation of the alternative pathway of complement on erythrocytes with an isolated deficiency of decay accelerating factor.
E from individuals with the Inab blood group phenotype have an isolated deficiency of decay accelerating factor (DAF, CD55). DAF is a glycosyl phosphatidylinositol anchored membrane protein that inhibits activation of both the classical and alternative pathways of complement. Deficiency of DAF from the E of paroxysmal nocturnal hemoglobinuria (PNH) is thought to contribute to their greater sensitivity to complement-mediated lysis. Unlike PNH E, however, Inab cells are not susceptible to acidified serum lysis, a process that is mediated through activation of the alternative pathway. This observation led us to hypothesize that membrane constituents other than DAF control susceptibility to acidified serum lysis. To investigate this hypothesis, Inab E were incubated in acidified serum, and hemolysis and C3 deposition (as a measure of alternative pathway activation) were quantitated. C3 deposition of Inab cells was approximately 20 times greater than normal, however, hemolysis was not observed. Inab E expressed a normal amount of membrane inhibitor of reactive lysis (MIRL, CD59), a glycosyl phosphatidylinositol anchored protein that is also deficient in PNH. When MIRL function was blocked with antibody, C3 deposition markedly increased, and 100% of the Inab cells hemolyzed in acidified serum. These studies demonstrate that susceptibility to acidified serum lysis is controlled primarily by MIRL, and that in addition to its regulatory affect on the membrane attack complex, MIRL also modulates the activity of the C3 convertase of the alternative pathway by a mechanism that remains to be determined.
Department of Medicine, University of Utah School of Medicine, Salt Lake City.
M H
MH
Holguin
C B
CB
Martin
N J
NJ
Bernshaw
C J
CJ
Parker
D000818:Animals; D015703:Antigens, CD / Q000097:blood; D001790:Blood Physiological Phenomena; D018958:CD55 Antigens; D018957:CD59 Antigens; D050577:Complement C3-C5 Convertases / Q000032:analysis; D003170:Complement Pathway, Alternative; D004912:Erythrocytes / Q000276:immunology*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood; D006461:Hemolysis; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood; D008565:Membrane Proteins / Q000032:analysis / Q000172:deficiency*; D011817:Rabbits; D011951:Receptors, Complement / Q000032:analysis; D017463:Receptors, Complement 3b
D015703:Antigens, CD; D018958:CD55 Antigens; D018957:CD59 Antigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D050577:Complement C3-C5 Convertases