Neutrophil extracellular traps and leukocyte-mediated tissue injury
THE CONTEXT
Activated leukocytes destroy microbes but can also injure normal tissues through extracellular release of antimicrobial substances.
Neutrophil extracellular traps
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Activated neutrophils release chromatin components, including histones, which form fibrillar networks called neutrophil extracellular traps (NETs).
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NETs bind and concentrate antimicrobial peptides and granule enzymes, creating extracellular sites for microbial destruction.
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During NET formation, neutrophils lose their nuclei and die.
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NETs can be detected in blood during sepsis because of widespread neutrophil activation.
Settings of tissue injury
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Leukocytes may injure normal tissues during defense against microbes, especially organisms resistant to eradication, such as mycobacteria.
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Responses directed against self antigens cause tissue injury in autoimmune diseases; responses against normally harmless environmental antigens cause injury in allergic diseases.
Mechanism and control
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Release of granule and lysosomal contents is the mechanism of leukocyte-mediated tissue injury.
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Release is exaggerated when phagocytes encounter material that cannot be readily ingested, such as antibodies deposited on indigestible flat surfaces.
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Ingested urate and silica crystals can damage phagolysosomal membranes and exaggerate the release of damaging contents.
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Antiproteases in blood and tissue fluids normally control harmful leukocyte proteases. Alpha-1 antitrypsin is the major inhibitor of neutrophil elastase; deficiency can permit sustained protease activity.