Phagocytosis and intracellular destruction of microbes
THE CONTEXT
Recruited neutrophils and monocytes are activated by microbial products, necrotic cells, and local cytokines to destroy microbes and clear dead tissue.
Principal phagocytes
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Phagocytosis is the ingestion of particulate material by cells. Neutrophils and macrophages are the body's most important phagocytes.
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Neutrophils respond rapidly but are relatively short lived. Macrophage responses are slower and more persistent.
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Macrophages in inflammatory reactions arise from blood monocytes and may survive for days or months. Some tissue-resident macrophages originate from embryonic precursors and remain for years.
Recognition and opsonization
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Phagocyte receptors recognize microbes directly. The mannose receptor recognizes terminal mannose residues in microbial glycoproteins; scavenger receptors also participate in recognition.
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Opsonization coats microbes with molecules recognized by specific phagocyte receptors and greatly increases the efficiency of ingestion.
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Opsonins include antibodies, the C3b cleavage product of complement, and certain plasma lectins.
Ingestion and killing
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After receptor binding, the particle enters a membrane-bound phagosome. Fusion with lysosomes delivers lysosomal contents into the resulting phagolysosome.
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Neutrophils may also release granule contents into the extracellular space during this process.
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Reactive oxygen species, reactive nitrogen species mainly derived from nitric oxide, and lysosomal enzymes destroy microbes and ingested debris.
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Compartmentalization of harmful substances away from the cytoplasm helps protect the phagocyte during its normal function.