Regulation of the amplification C3 convertase of human complement by an inhibitory protein isolated from human erythrocyte membrane

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Abstract
An activity that is inhibitory to the properdin-stabilized amplification C3 [complement component 3] convertase (C3b,Bb,P) was solubilized from human erythrocyte (Ehu) membranes by Nonidet P-40 and purified to homogeneity. The inhibitory membrane glycoprotein had an apparent MW of 1-1.2 .times. 106 on gel filtration in the presence of Nonidet P-40. On sodium dodecyl sulfate/polyacrylamide gel electrophoresis it presented a single stained band with an apparent MW of 205,000, with or without prior reduction of disulfides. The inhibitory protein of the Ehu membrane produced a dose-related, 1st-order decay of C3b,Bb,P function on sheep erythrocytes (Es) and released 125I-labeled Bb from these sites, indicating a mechanism of inhibition by decay-dissociation of the amplification C3 convertase. The 50% inhibitory dose of the Ehu membrane protein was not altered by removal of sialic acid from the Es bearing C3b,Bb,P sites. Ehu membrane protein also served as a cofactor for C3b inactivator-induced cleavage of the .alpha. polypeptide chain of C3b. The inhibitory membrane protein can abrogate activity of amplification convertase sites that have formed and also can prevent generation of such sites by augmenting irreversible inactivation of C3b. Discrimination between cells by the alternative pathway occurs after initial deposition of C3b and is related to modulation by surface constituents of the capacity of bound C3b to function as a subunit of the amplification C3 convertase. Existence in the Ehu membrane of a protein that can impair functions of membrane-bound C3b and C3b,Bb,P could represent a molecular basis for preventing inappropriate self-recognition.

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