The objective of this work is to further define the physiologic mechanisms that regulate complement and immunoglobulin mediated phagocytosis. This laboratory has previously studied some of the cellular events that render a polymorphonuclear leukocyte or macrophage able to phagocytose via CR1, the receptor for the C3b fragment of the complement component C3. In resting neutrophils, this receptor does not mediate internalization or phagocytosis. However, when neutrophils are treated with phorbol esters, CR1 acquires two new activities: a) the ability to cause phagocytosis of C3b-coated particles, and b) a continuous and ligand-independent endocytic process. We have studied the fate of CR1 ligands and the receptor inside the cell following phorbol ester treatment. We have found that C3b CR1 complexes are recycled to the cell surface through a pre-lysosomal, pre-acidic compartment and that this compartment is associated with a low density membrane component. However, when CR1 is crosslinked, the recycling is slowed and diminished, and a different compartment of greater density containing the ligand is demonstrated. Future directions include the morphologic and kinetic characterization of this pathway in the cell, and its impact on phagocytosis mediated by a combination of Fc and CR1 receptors.
