Reduced activity of DAF on complement enzymes bound to alternative pathway activators. Similarity with Factor H.
Attachment of C3b to activators of the alternative pathway of complement results in a decrease in regulatory activity expressed by Factor H. Decay-accelerating factor (DAF) and Factor H were found to exhibit quantitatively similar decreases in regulatory activity toward the C3 convertase (C3b,Bb) bound to activators, such as zymosan (Zym) and rabbit erythrocytes (ER), compared to non-activators, such as sheep (ES) and bovine (EB) erythrocytes. Purified DAF and Factor H, in 0.1% NP-40, were assayed by measuring the amount required to release 50% of the radiolabelled Bb in 10 min from C3b,Bb on Zym or cross-linked erythrocytes. The relative effectiveness (i.e. the restriction index, RI) of DAF for accelerating the decay of C3b,Bb on the various particles was: ES (1.0), ER (0.04) and Zym (0.03). The RI for Factor H was: ES (1.0), ER (0.04) and Zym (0.07). The rate of decay of C3b,Bb induced by DAF and Factor H showed similar restriction. The results suggest that the regulatory properties of DAF are reduced if the cells on which it resides become activators of the alternative pathway as a result of transformation, virus infection or surface alteration. These findings may explain reports of dysfunctional DAF on alternative pathway-activating cells.
Pangburn
M K
MK
Department of Biochemistry, University of Texas Health Science Center, Tyler 75710.
D000818:Animals; D018958:CD55 Antigens; D050577:Complement C3-C5 Convertases / Q000378:metabolism*; D003180:Complement C3b Inactivator Proteins / Q000502:physiology*; D017242:Complement Factor H; D003169:Complement Inactivator Proteins / Q000502:physiology*; D003170:Complement Pathway, Alternative / Q000502:physiology*; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D011817:Rabbits; D015054:Zymosan / Q000378:metabolism
D018958:CD55 Antigens; C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D003169:Complement Inactivator Proteins; D008565:Membrane Proteins; D017242:Complement Factor H; D015054:Zymosan; D050577:Complement C3-C5 Convertases