Studies on the Mechanism of Phagocytosis

Phagocytic leukocytes have on their plasma membranes receptors for the Fc portion of immunoglobulin G (IgG) (1-9) and for a cleavage product of the third component of complement (C3) (3-5, 8, 10-15). Particles coated with IgG or C3 attach to the corresponding receptors on the plasma membranes of phagocytic cells. We have been studying the roles of these ligands (IgG and C3) and of their receptors in the ingestion phase of phagocytosis. We reported previously (16) that removal of ligands or blockade of receptors lying outside the zone of attachment of immunologically coated erythrocytes to the plasma membranes of mouse peritoneal macrophages prevented the ingestion of these erythrocytes. These findings led us to propose that the ingestion of a particle requires the sequential, circumferential interaction of phagocytic receptors with particlebound ligands not involved in the initial attachment of the particle to the phagocytic cell. We termed this process the ~'zipper" mechanism of phagocytosis (16). In our previous experiments, we altered ligands on the erythrocytes or blocked receptors on the macrophages. Thus, it was conceivable that our experimental procedures reduced the number of ligand-receptor bonds in the zone of attachment of the erythrocytes to the macrophages below some critical level necessary to trigger ingestion of the erythrocytes. Had this occurred, our interpretation of those experiments would be open to serious doubt. Several lines of evidence suggested that this possibility was unlikely; nevertheless, it could not be excluded. The experiments described in the present report were designed to eliminate these quantitative ambiguities and thereby to test rigorously the validity of the zipper mechanism. In the present study we have used as phagocytic test particles bone marrow derived lymphocytes. These cells bear immunoglobulin molecules on their plasma membranes. Incubation of these lymphocytes at 25°C with anti-immunoglobulin IgG promotes capping; that is, the redistribution of nearly all surface immunoglobulin molecules from their random distribution on the lymphocyte's plasma membrane to only one arc of its circumference. We found that when