The REACTION MECHANISM OF SS1C-Globulin (C'3) IN IMMUNE HEMOLYSIS

Abstract

In addition to being part of the classical third component of complement, /31c-globulin (1) has been shown to play a key role in the mechanism of immune adherence (2), conglutination, immune conglutination (3), and erythrophagocytosis in vitro (4) and in vivo (5).Since the various functions of/3m-globtflin appear to depend upon attachment of the protein to the erythrocyte surface, a study was carried out with the aim (a) to delineate the mechanism of transfer of file-globulin from the fluid phase to cell membrane receptor sites, and (b) to evaluate quantitatively the functional significance of cell-bound/3it-globulin. This work became feasible through the development of an improved method of isolation of file-globulin (6) and the use of a radioactive label which permitted detection and quantitation of minute amounts of this protein on cell membranes and in free solution.Evidence will be presented indicating (a) that uptake of/3at-globulin by cells is effected by an enzymatic process in which flat-globulin behaves like substrate and the activated second component of complement like an enzyme moiety, and (b) that immune hemolysis and immune adherence necessitate binding of a multiplicity of fl~c-molecules per cell.Work in this laboratory (6, 7), and in others (8-11), has revealed that the classical third component of complement consists of a number of different serum factors and that/3~c-globulin represents only one of the factors of this group. According to a recently proposed nomenclature (7, 12), these factors are called components three (C'3), five (C'5), six (C'6), etc., C'3 being synonymous with tic-globulin and no longer with the classical third component. Henceforth, the term C'3 will be used exclusively to denote file-globulin and its hemolytic activity.

Studies of the In Vivo Behavior of Human C′3 in Normal Subjects and Patients*

“…This finding confirms the observation that labeling with radioactive iodine does not alter the complement activity of C'3 (21). Preparation of labeled C'3,.…”

Evidence for In Vivo Breakdown of β1C-Globulin in Hypocomplementemic Glomerulonephritis *

“…The roles of P1c deposition and of diminished synthesis in keeping concentrations low cannot be defined by the present study. 1 The present observations coincide with the investigations of Muller-Eberhard and associates (6), who used radiolabeled /81c in detailed studies 1 In vivo breakdown of jic and persistence of breakdown products in the circulation could introduce error in the isotopic measurement of pic disappearance. If the portion of the molecule that yielded alpha2D were isotopically labeled, the breakdown product would contribute counts and the half-life calculated for jc would be erroneously long.…”

Breakdown products of C′3 in human synovial fluids

“…In vitro studies of the reaction mechanism of C'3 in immune hemolysis have shown that only 5-10% of the available C'3 attaches to red blood cells or antigen-antibody complexes. The remainder (90-95%) of whole serum C'3 is converted to C'3i (21). It appears likely that during in vivo complement activation C'3 is converted to C'3i in the plasma or extravascular spaces, and only a small proportion of the C'3 is fixed to tissues.…”