Studies of the Mechanism of Phagocytosis
A central problem in modern biology is how signals initiated at the cell’s surface alter cellular behavior. Mononuclear phagocytes are superb tools for studying this question. These cells have on their surfaces receptors for the Fc fragment of immunoglobulin G (IgG) and for the third component of complement (C3). Particles coated with these immunologically determined ligands bind via these ligands to macrophage membrane receptors. Signals generated by the interaction of particle bound ligands with their corresponding membrane receptors promote pseudopod extension and particle engulfment. As a phagocytic vacuole forms, the plasma membrane must rearrange its structure to form a sphere from a relatively flat sheet. When the advancing pseudopods meet to seal the phagocytic vacuole they fuse selectively with one another and not with membrane processes of adjacent cells. The speed and magnitude of the phagocytic process is also impressive. Within a span of 10–15 min these cells can engulf sufficient particles to cause interiorization of 30–50% of the macrophage surface area. How are these processes regulated? What coordinates membrane movement and remodelling? How are signals that are initiated at the cell’s surface transmitted to the cytoskeleton? We are trying to answer these questions by studying the phagocytosis of IgG or complement coated erythrocytes. Erythrocytes coated with these serum ligands are easy to prepare. By measuring whether these ligand coated erythrocytes bind to the macrophages we can identify the presence of receptors for IgG or for complement. By measuring whether the erythrocytes are ingested by the macrophages we can test for delivery of a transmembrane signal, i.e. the signal to phagocytose a particle.
KeywordsLactate Leukemia Lysine Trypsin Calorimetry
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