Isolation of Variants in Phagocytosis

Phagocytosis has long been recognized as one of the differentiated functions of the macrophage and yet many of the cellular and biochemical mechanisms underlying this process remain unclear. Rabinovitch has separated the process of phagocytosis into two phases: attachment and ingestion (1). The former is dependent both on the surface properties of the cell and on the particle and is independent of energy and divalent cations, while the ingestion phase requires energy and divalent cations. Attachment can be mediated through binding to receptors on the macrophage surface for the C3 component of complement and the Fc portion of immunoglobulins. In studies on Fc-mediated and C3-mediated phagocytosis, Griffin et al. (2) observed that a particle will be ingested only if the macrophage receptors for that particle are able to bind the entire surface of the particle. Thus, the initial necessary attachment at a single site is not sufficient for phagocytosis, but binding must occur on other sites of the particle during ingestion. In addition, these investigators found that erythrocytes attached to the macrophage surface with cross-linking antibody would not be ingested during the phagocytosis of other particles (3). Thus, phagocytosis was shown to occur not through a general activation of the membrane but rather through a localized or segmental response. In further studies, Griffin et al. demonstrated that particles bound to the macrophages by the C3 receptors were not phagocytized coincidentally during phagocytosis mediated through the Fc receptor (4). These studies have greatly extended our understanding of Fc-mediated phagocytosis by describing the selective interactions between particles and the phagocytic cell and additionally by distinguishing various types of phagocytosis: nonspecific phagocytosis, Fc-mediated phagocytosis, and C3-mediated phagocytosis, the latter being carried out exclusively by activated macrophages (5).