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phagocytosis

Friday 23 April 2004

Definition: Phagocytosis is a specific form of endocytosis involving the vesicular internalization of solid particles, such as bacteria. It is therefore distinct from other forms of endocytosis such as pinocytosis, the vesicular internalization of various liquids, and recptor-dependent endocytosis.

Phagocytosis (literally, cell-eating) is the process by which cells ingest large objects, such as cells which have undergone apoptosis, bacteria, or viruses. The membrane folds around the object, and the object is sealed off into a large vacuole known as a phagosome.

Phagocytosis is the cellular process of engulfing solid particles by the cell membrane to form an internal phagosome, or "food vacuole." The phagosome is usually delivered to the lysosome, an organelle involved in the breakdown of cellular components, which fuses with the phagosome. The contents are subsequently degraded and either released extracellularly via exocytosis, or released intracellularly to undergo further processing.

Phagocytosis is involved in the acquisition of nutrients for some cells, and in the immune system it is a major mechanism used to remove pathogens and cell debris. Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytosed.

Phagocytosis and the release of enzymes by neutrophils and macrophages are responsible for eliminating the injurious agents and thus constitute two of the major benefits derived from the accumulation of leukocytes at the inflammatory focus.

Recognition and Attachment

Although neutrophils and macrophages can engulf bacteria or extraneous matter (e.g., latex beads) without attachment to specific receptors, typically the phagocytosis of microbes and dead cells is initiated by recognition of the particles by receptors expressed on the leukocyte surface.

Mannose receptors and scavenger receptors are two important receptors that function to bind and ingest microbes. The mannose receptor is a macrophage lectin that binds terminal mannose and fucose residues of glycoproteins and glycolipids.

These sugars are typically part of molecules found on microbial cell walls, whereas mammalian glycoproteins and glycolipids contain terminal sialic acid or N-acetylgalactosamine.

Therefore, the macrophage mannose receptor recognizes microbes and not host cells. Scavenger receptors were originally defined as molecules that bind and mediate endocytosis of oxidized or acetylated low-density lipoprotein (LDL) particles that can no longer interact with the conventional LDL receptor.

Macrophage scavenger receptors bind a variety of microbes in addition to modified LDL particles. Macrophage integrins, notably Mac-1 (CD11b/CD18), may also bind microbes for phagocytosis.

The efficiency of phagocytosis is greatly enhanced when microbes are opsonized by specific proteins (opsonins) for which the phagocytes express high-affinity receptors.

As described above, the major opsonins are IgG antibodies, the C3b breakdown product of complement, and certain plasma lectins, notably MBL, all of which are recognized by specific receptors on leukocytes.

Engulfment

Binding of a particle to phagocytic leukocyte receptors initiates the process of active phagocytosis of the particle. During engulfment, extensions of the cytoplasm (pseudopods) flow around the particle to be engulfed, eventually resulting in complete enclosure of the particle within a phagosome created by the plasma membrane of the cell.

The limiting membrane of this phagocytic vacuole then fuses with the limiting membrane of a lysosomal granule, resulting in discharge of the granule’s contents into the phagolysosome. During this process, the neutrophil and the monocyte become progressively degranulated.

The process of phagocytosis is complex and involves the integration of many receptor-initiated signals with the coordinated orchestration of membrane remodeling and cytoskeletal changes.

Phagocytosis is dependent on polymerization of actin filaments; it is, therefore, not surprising that the signals that trigger phagocytosis are many of the same that are involved in chemotaxis. (In contrast, fluid phase pinocytosis and receptor-mediated endocytosis of small particles involve internalization into clathrin-coated pits and vesicles and are not dependent on the actin cytoskeleton.)

Killing and Degradation

The ultimate step of bacterial phagocytosis in the elimination of infectious agents and necrotic cells is their killing and degradation within neutrophils and macrophages, which occur most efficiently after activation of the phagocytes.

Microbial killing is accomplished largely by oxygen-dependent mechanisms. Phagocytosis stimulates a burst in oxygen consumption, glycogenolysis, increased glucose oxidation via the hexose-monophosphate shunt, and production of reactive oxygen intermediates (ROS, also called reactive oxygen species).

Phagocytosis involves three distinct but interrelated steps:

  • (1) recognition and attachment of the particle to be ingested by the leukocyte;
  • (2) its engulfment, with subsequent formation of a phagocytic vacuole;
  • (3) killing or degradation of the ingested material.

- Bacteria phagocytosed by leukocytes are killed and degraded by toxic oxygen metabolites produced in the phagosome via an NADPH oxidase. NADPH oxidase activity is regulated by small GTP-binding proteins in response to phagocytic stimuli.

Pathology

- phagocytes defects

  • phagocyte respiratory burst defects

See also

- phagosomes

  • phagosome membrane

- ER-mediated phagocytosis
- phagocyte respiratory burst

References

- Hallett MB, Dewitt S. Ironing out the wrinkles of neutrophil phagocytosis. Trends Cell Biol. 2007 Mar 9; PMID: #17350842#

- Desjardins M, Griffiths G. Phagocytosis: latex leads the way. Curr Opin Cell Biol. 2003 Aug;15(4):498-503. PMID: #12892792#

- Isberg RR, Van Nhieu GT. The mechanism of phagocytic uptake promoted by invasin-integrin interaction. Trends Cell Biol. 1995 Mar;5(3):120-4. PMID: #14732167#

- Bokoch GM. Regulation of the phagocyte respiratory burst by small GTP-binding proteins. Trends Cell Biol. 1995 Mar;5(3):109-13. PMID: #14732165#

- Beron W, Alvarez-Dominguez C, Mayorga L, Stahl PD. Membrane trafficking along the phagocytic pathway. Trends Cell Biol. 1995 Mar;5(3):100-4. PMID: #14732163#

- Greenberg S. Signal transduction of phagocytosis. Trends Cell Biol. 1995 Mar;5(3):93-9. PMID: #14732162#

- Swanson JA, Baer SC. Phagocytosis by zippers and triggers. Trends Cell Biol. 1995 Mar;5(3):89-93. PMID: #14732161#