Phagocytosis is important in most animals for purposes other than nutrition, and it is carried out mainly by specialized cells—so-called professional phagocytes. In mammals, two important classes of white blood cells that act as professional phagocytes are macrophages and neutrophils (Movie 13.5). These cells develop from hemopoietic stem cells (discussed in Chapter 22), and they ingest invading microorganisms to defend us against infection. Macrophages also have an important role in scavenging senescent cells and cells that have died by apoptosis (discussed in Chapter 18). In quantitative terms, the clearance of senescent and dead cells is by far the most important: our macrophages, for example, phagocytose more than 1011 senescent red blood cells in each of us every day.
The diameter of a phagosome is determined by the size of its ingested particles, and those particles can be almost as large as the phagocytic cell itself (Figure 13–60). Phagosomes fuse with lysosomes, and the ingested material is then degraded. Indigestible substances remain in the lysosomes, forming residual bodies that can be excreted from cells by exocytosis, as mentioned earlier. Some of the internalized plasma membrane components never reach the lysosome, because they are retrieved from the phagosome in transport vesicles and returned to the plasma membrane.
Some pathogenic bacteria have evolved elaborate mechanisms to prevent phagosome–lysosome fusion. The bacterium Legionella pneumophila, for example, which causes Legionnaires’ disease (discussed in Chapter 23), injects into its unfortunate host a Rab-modifying enzyme that causes certain Rab proteins to misdirect membrane traffic, thereby preventing phagosome–lysosome fusion. The bacterium, thus spared from lysosomal degradation, remains in the modified phagosome, growing and dividing as an intracellular pathogen, protected from the host’s adaptive immune system.
Phagocytosis is a cargo-triggered process. That is, it requires the activation of cell-surface receptors that transmit signals to the cell interior. Thus, to be phagocytosed, particles must first bind to the surface of the phagocyte (although not all particles that bind are ingested). Phagocytes have a variety of cell surface receptors that are functionally linked to the phagocytic machinery of the cell. The best-characterized triggers of phagocytosis are antibodies, which protect us by binding to the surface of infectious microorganisms (pathogens) and initiating a series of events that culminate in the invader being phagocytosed. When antibodies initially attack a pathogen, they coat it with antibody molecules that bind to Fc receptors on the surface of macrophages and neutrophils, activating the receptors to induce the phagocytic cell to extend pseudopods, which engulf the particle and fuse at their tips to form a phagosome (Figure 13–61A). Localized actin polymerization, initiated by Rho family GTPases and their activating Rho-GEFs (discussed in Chapters 15 and 16), shapes the pseudopods. The activated Rho GTPases switch on the kinase activity of local PI kinases to produce PI(4,5)P2 in the membrane (see Figure 13–11), which stimulates actin polymerization. To seal off the phagosome and complete the engulfment, actin is depolymerized by a PI 3-kinase that converts the PI(4,5)P2 to PI(3,4,5)P3, which is required for closure
Figure 13–60 Phagocytosis by a macrophage. a scanning electron micrograph of a mouse macrophage phagocytosing two chemically altered red blood cells. The red arrows point to edges of thin processes (pseudopods) of the macrophage that are extending as collars to engulf the red cells. (courtesy of Jean paul revel.)