Role of human factor I and C3b receptor in the cleavage of surface‐bound C3bi molecules

Abstract

Control of functions mediated by the third component of complement (C3) depends on the rate of generation and degradation of biologically active C3 fragments. To evaluate the mechanisms of degradation of active C3 fragments, the role of the control protein C3b/C4b inactivator (factor I) was investigated under conditions approximating those found in vivo, i.e. in the presence of plasma. The breakdown of human erythrocyte-bound C3bi molecules in serum or plasma was mediated only by factor I, since factor I-deficient or -depleted plasma was inactive until reconstituted with highly purified factor I. The rate of cleavage of C3bi bound to human erythrocytes by purified factor I was not affected by the presence or absence of beta 1H (factor H). The released breakdown product of C3bi has been shown to be C3c antigenically and on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Two different monospecific antibodies to the human C3b receptor totally abrogated factor I-mediated cleavage of cell-bound C3bi, suggesting that the C3b receptor (but not factor H) is required as an obligate cofactor. The rate of this C3b receptor-dependent, factor I-mediated cleavage of bound C3bi is strongly regulated by the surface to which C3bi is bound. Whereas C3bi bound to particulate nonactivators of the alternative complement pathway such as human erythrocytes is rapidly degraded by this mechanism, the rate of cleavage of C3bi bound to activators is significantly slower. These data suggest a physiologic role of C3b receptors in the degradation of biologically active C3 fragments deposited on host tissues. They also suggest that C3bi molecules on restricted surfaces are relatively stable and can thereby interact with complement C3 receptors in vivo.

Deficiency of a surface membrane glycoprotein (Mo1) in man.

“…3), in agreement with in vitro studies in which pretreating PBL with anti-Mac-l (27) On normal cells, anti-Mo 1, anti-Mac-I or anti-OKM10 effectively blocked C3bi receptor-depedent rosette formation suggesting that Mol/Mac-l/OKMl are closely associated (3,4) or identical (28) with the C3bi receptor. It has also been suggested that EAC43bi can bind to the C3b receptor (29,30,31 Structural studies revealed that the patient's cells were deficient in the two subunits of Mol antigen (Fig. 1).…”

Demonstration of Factor H-Like Protein 1 Binding toTreponema denticola, a Pathogen Associated with Periodontal Disease in Humans

“…Factor I is a serine protease that cleaves C3b at its serine residues, yielding a specific cleavage pattern (14,26). The C3b cleavage assay employed here was previously employed by McDowell and colleagues to demonstrate the complement regulatory activity of factor H bound to the relapsing fever spirochetes B. hermsii and Borrelia parkeri and the Lyme disease spirochete, B. burgdorferi (23).…”

Altered erythrocyte C3b receptor expression, immune complexes, and complement activation in homosexual men in varying risk groups for acquired immune deficiency syndrome.

“…CR1 appears to endow these cells with the capacity to clear circulating immune complexes (CIC)' by transporting them to the liver where they are removed by local macrophages (8,9). In addition, CR1 acts as cofactor of factor I in the inactivation of C3b and C4b (2,(10)(11)(12).…”