Phagolysosomal killing and leukocyte granule contents
THE CONTEXT
Phagocytosis brings microbes into intracellular compartments where granule enzymes and reactive oxygen and nitrogen species destroy them.
Sequence of phagocytosis and destruction
•
Phagocytosis involves binding of a particle to leukocyte membrane receptors, engulfment, and fusion of phagocytic vacuoles with lysosomes.
•
Ingested particles are destroyed within phagolysosomes by lysosomal enzymes and reactive oxygen and nitrogen species.
•
In activated phagocytes, cytoplasmic components of phagocyte oxidase assemble in the phagosomal membrane to form the active enzyme, which converts oxygen into superoxide and hydrogen peroxide.
•
Myeloperoxidase in neutrophil granules converts hydrogen peroxide to hypochlorite.
•
Granule contents may also be released into extracellular tissues during phagocytosis.
Neutrophil granule types
•
Smaller specific, or secondary, granules contain lysozyme, collagenase, gelatinase, lactoferrin, plasminogen activator, histaminase, and alkaline phosphatase.
•
Larger azurophil, or primary, granules contain myeloperoxidase, bactericidal factors such as defensins, acid hydrolases, and neutral proteases.
•
The neutral proteases in primary granules include elastase, cathepsin G, nonspecific collagenases, and proteinase 3.
•
Activation of neutrophils releases the contents of both granule types. Granule enzymes can also contribute to tissue damage.
•
Phagocytic vesicles can fuse with granules and lysosomes, allowing their enzymes to destroy engulfed material within phagolysosomes.
Macrophage lysosomal enzymes
•
Macrophage lysosomes contain acid hydrolases, collagenase, elastase, and phospholipase, which can destroy ingested material and cell debris.