The Enhancement of Bacterial Phagocytosis by Serum

Abstract

When Metchnikoff defined the process of phagocytosis in 1884 (1, 2), he conceded to serum the minor role of an dement that merely modified the phagocyte. However, in 1903 Wright and Douglas clearly established that phagocytosis of pathogenic bacteria could not occur without serum; that this effect was achieved by modification of the microorganism rather than the phagocyte; and that immunity developed in the serum, not the leukocyte (3, 4). Whether this serum effect was accomplished by specific antibody alone or by antibody acting in conjunction with a nonspecific, heat-labile serum activity, namely complement, was not dear until the experiments of Ward and Enders in 1933. They demonstrated that ingestion of pneumococci could occur slowly in the presence of heated immune serum; however, the addition of small amounts of fresh, nonimmune serum markedly enhanced the rote of ingestion (5).The heat-labile factor or factors necessary for optimal phagocytosis of bacteria have not been precisely identified. On the basis of their own and other available experimental data, Boyden et al. found it impossible to define the role of thermolabile factors as opsonins and pointed out the need for a means of accurately measuring phagocytosis of bacteria (6). The present report describes a spectrophotometric method of measuring bacterial phagocytosis and its application to demonstrate that the first four components of human complement and two serum cofactors are necessary for the optimal phagocytosis of pneumococci by human leukocytes.

The Relationship Between Group a and Group C Meningococcal Polysaccharides and Serum Opsonins in Man

“…Phagocytosis of pneumococci in the presence of type-specific opsonins and heat-labile factors has recently been reported by Johnston, Klemperer, Alper, and Rosen (23). These authors demonstrated that optimal phagocytosis of pneumococci requires 7S antibody, the first four components of complement, a heat-labile, dialyzable cofactor and a heat-labile, 5-6S, beta pseudoglobulin.…”

The Interaction Between Human Monocytes and Red Cells

“…IgM agglutinins in the presence of complement have been observed to form mixed aggregates (12), but red cells coated only with C3 did not adhere to monocytes. Cell-bound C3 may possess peptidase activity (23), which appears to be critical for the mediation of phagocytosis (24). It is possible that C3 enhances phagocytosis not because of a specific cellular receptor but rather because of the peptidase activity of activated C3.…”

The internal thioester and the covalent binding properties of the complement proteins C3 and C4

“…This was interpreted as indicating that the interaction between activated C3 fragments and the target surface components was a very strong hydrophobic one. Another phenomenon, which was not addressed in a coherent manner, was the means by which C3b could bind to so wide a range of unrelated surfaces, including cell membranes Dalmasso & MullerEberhard, 1967), bacterial cell wall components (Johnston et al, 1969), immune aggregates (Theofilopoulos et al, 1974;Czop & Nussenzweig, 1976), zymosan (a large mannan complex from yeast cell walls) (Nicholson et al, 1974), and the artificial particle Sepharose (Goldstein et al, 1976). The key experiment, which provided the first evidence for the covalent binding of C3, was the analysis, by SDS-PAGE, of the membrane polypeptides of sheep erythrocytes after they had been treated sequentially with antibody, CI, C4, C2, and '251-labeled C3.…”