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[General pathology](https://durgical.com/en/general-pathology/) · [Inflammation](https://durgical.com/en/general-pathology/#a-inflammation)

# When leukocytes injure tissue: proteases, oxidants and NETs

- Mechanism

The weapons neutrophils use to kill microbes (enzymes, oxidants and DNA nets) can leak out and damage the body's own tissue.

Updated 2026-11-01

## Key points

- Neutrophil weapons: NADPH oxidase (superoxide), myeloperoxidase (hypochlorous acid), elastase and other proteases, NETs.
- Frustrated phagocytosis at large targets (immune complexes, crystals) releases enzymes outward.
- ARDS and immune-complex glomerulonephritis are neutrophil-mediated injuries.
- Alpha-1 antitrypsin deficiency: unopposed elastase → panacinar emphysema.
- NETs trap microbes but also favour thrombosis and expose nuclear autoantigens (lupus).

## What it is

Neutrophils and macrophages kill microbes inside phagolysosomes with reactive oxygen species and enzymes, and can expel sticky webs of DNA (neutrophil extracellular traps, NETs). These products are not perfectly contained: they leak during phagocytosis, are released onto targets too large to swallow, or spill when the cell dies. This collateral damage is the main way tissue is injured in ARDS, immune-complex disease, gout and some vasculitides.

## Key facts

- Antiproteases (alpha-1 antitrypsin, alpha-2 macroglobulin) and antioxidants (superoxide dismutase, catalase, glutathione peroxidase) normally limit the damage.
- Tobacco smoke recruits neutrophils and its oxidants inactivate alpha-1 antitrypsin, which speeds up emphysema.
- Chronic granulomatous disease is the opposite problem: without NADPH oxidase, neutrophils cannot kill catalase-positive microbes.

## Step by step

- Activated neutrophils assemble NADPH oxidase (respiratory burst), making superoxide and then hydrogen peroxide.
- Myeloperoxidase turns hydrogen peroxide and chloride into hypochlorous acid, a powerful oxidant.
- Granules release elastase, collagenases (matrix metalloproteinases) and cathepsins into phagosomes; some leak out.
- Frustrated phagocytosis: at targets too large to engulf (immune complexes on basement membranes, crystals) the cell releases its contents outward.
- In NETosis the neutrophil decondenses its chromatin (PAD4 citrullinates histones) and expels a web of DNA, histones and enzymes.
- Unopposed proteases and oxidants damage endothelium, matrix and epithelium; NETs also promote thrombosis.

## Leukocyte-mediated injury in disease

| Disease | Main mechanism |
| --- | --- |
| [Acute respiratory distress syndrome](https://durgical.com/en/conditions/acute-respiratory-distress-syndrome/) | Neutrophils in alveolar capillaries release proteases and oxidants that damage alveolar walls; protein-rich fluid floods the alveoli |
| [Gout](https://durgical.com/en/conditions/gout/) | Urate crystals activate the NLRP3 inflammasome (IL-1β) and cause frustrated phagocytosis by neutrophils |
| [Rheumatoid arthritis](https://durgical.com/en/conditions/rheumatoid-arthritis/) | Neutrophils in synovial fluid and macrophages in the pannus release enzymes that erode cartilage and bone |
| [Post-streptococcal glomerulonephritis](https://durgical.com/en/conditions/post-streptococcal-glomerulonephritis/) | Immune complexes in glomeruli activate complement and attract neutrophils |
| [Granulomatosis with polyangiitis](https://durgical.com/en/conditions/granulomatosis-with-polyangiitis/) | ANCA activate neutrophils that injure small vessel walls |
| [Systemic lupus erythematosus](https://durgical.com/en/conditions/systemic-lupus-erythematosus/) | Poorly cleared NETs and dead cells supply nuclear autoantigens |
| [Alpha-1 antitrypsin deficiency](https://durgical.com/en/conditions/1-antitrypsin-deficiency/) | Neutrophil elastase is unopposed and destroys alveolar walls (panacinar emphysema) |

## Memory aid

Friendly fire: the neutrophil's bleach (hypochlorous acid), scissors (elastase) and fishing net (NETs) do not check uniforms.

## Test yourself

Think of the answer, then tap the question to see it.

## What is frustrated phagocytosis?

Release of granule enzymes and oxidants outside the cell when a neutrophil tries to engulf a target too large to ingest, such as immune complexes on a basement membrane.

## Which enzyme makes hypochlorous acid in neutrophils?

Myeloperoxidase, from hydrogen peroxide and chloride ions.

## Why does alpha-1 antitrypsin deficiency cause emphysema?

Neutrophil elastase in the lung is left unopposed and digests the elastic tissue of the alveolar walls.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/when-leukocytes-injure-tissue-proteases-oxidants-and-nets/)

## Related

- [Leukocyte recruitment: rolling, adhesion, transmigration, chemotaxis](https://durgical.com/en/general-pathology/leukocyte-recruitment-rolling-adhesion-transmigration-chemotaxis/)
- [Mediators of inflammation: the table to know](https://durgical.com/en/general-pathology/mediators-of-inflammation-the-table-to-know/)
- [Oxidative stress and free-radical injury](https://durgical.com/en/general-pathology/oxidative-stress-and-free-radical-injury/)
- [Outcomes of acute inflammation: resolution, abscess, scar or chronic inflammation](https://durgical.com/en/general-pathology/outcomes-of-acute-inflammation-resolution-abscess-scar-or-chronic-inflammation/)
- [Chronic inflammation: causes, cells and features](https://durgical.com/en/general-pathology/chronic-inflammation-causes-cells-and-features/)

## Related conditions

- [Acute respiratory distress syndrome (ARDS)](https://durgical.com/en/conditions/acute-respiratory-distress-syndrome/)
- [Rheumatoid arthritis](https://durgical.com/en/conditions/rheumatoid-arthritis/)
- [Gout](https://durgical.com/en/conditions/gout/)
- [Systemic lupus erythematosus](https://durgical.com/en/conditions/systemic-lupus-erythematosus/)
- [α1-antitrypsin deficiency](https://durgical.com/en/conditions/1-antitrypsin-deficiency/)
- [Chronic obstructive pulmonary disease (COPD)](https://durgical.com/en/conditions/chronic-obstructive-pulmonary-disease/)
- [Granulomatosis with polyangiitis](https://durgical.com/en/conditions/granulomatosis-with-polyangiitis/)
- [Post-streptococcal glomerulonephritis](https://durgical.com/en/conditions/post-streptococcal-glomerulonephritis/)
- [Chronic granulomatous disease](https://durgical.com/en/conditions/chronic-granulomatous-disease/)

## Elsewhere in DurgiPedia

- [Phagocytosis and the respiratory burst](https://durgical.com/en/immunology/phagocytosis-and-the-respiratory-burst/)
- [Neutrophil](https://durgical.com/en/immunology/neutrophil/)
- [Type III hypersensitivity (immune complexes)](https://durgical.com/en/immunology/type-iii-hypersensitivity/)
- [Reactive oxygen species and antioxidants](https://durgical.com/en/biochemistry/topics/reactive-oxygen-species-and-antioxidants/)
- [Superoxide dismutase (SOD)](https://durgical.com/en/biochemistry/enzymes/superoxide-dismutase/)
- [Phagocyte defects: CGD, LAD, Chédiak–Higashi](https://durgical.com/en/immunology/phagocyte-defects-cgd-lad-chediak-higashi/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Acute Respiratory Distress Syndrome](https://www.ncbi.nlm.nih.gov/books/NBK436002/) (StatPearls (NCBI Bookshelf), 2024); [Chronic granulomatous disease: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/chronic-granulomatous-disease/) (MedlinePlus, US National Library of Medicine, 2026); [17.5 Inflammation and Fever](https://openstax.org/books/microbiology/pages/17-5-inflammation-and-fever) (OpenStax (Microbiology), 2016).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/when-leukocytes-injure-tissue-proteases-oxidants-and-nets/