Neutrophils and their degranulation sequence
Neutrophils are the first to arrive at the site of inflammation. Their granular apparatus includes four types of vesicles that are released in a strict sequence upon cell stimulation:
- Secretory vesicles: released first, contain alkaline phosphatase, and are responsible for contact with the microenvironment.
- Gelatinase (tertiary) granules: secrete the enzyme gelatinase. This is necessary for collagen degradation, allowing the neutrophil to cross vascular basement membranes during migration into tissues.
- Specific (secondary) granules: fuse with the formed phagosome approximately 30 seconds after microorganism engulfment. They contain lysozyme, lactoferrin, and NADPH oxidase components, providing the rapid phase of bacteriolysis.
- Azurophilic (primary) granules: join the process after 1–3 minutes. Their markers are the enzyme myeloperoxidase and the CD63 molecule. They contain defensins, cathelicidins, acid hydrolases, and neutral proteases (cathepsin G, elastase, collagenase, azurocidin), accounting for the slow phase of bacterial destruction.
Granule contents (especially primary ones) can be released into the extracellular environment — a process known as degranulation. It is important to remember that a neutrophil uses its arsenal only once: after degranulation, new organelles are not regenerated.
Eosinophil, basophil, and NK cell granules
Different subpopulations of myeloid cells have a specific set of granules adapted to their unique biological tasks:
- Eosinophils. Contain several types of granules. Specific (large) granules contain major basic protein, cationic protein, neurotoxin, collagenase, and cytokines (GM-CSF, TNFα, IL-2, IL-4, IL-6) for extracellular cytolysis. Small granules provide bactericidal activity via arylsulfatase B and acid phosphatase. Primary granules accumulate lysophospholipase in the form of Charcot–Leyden crystals (involved in lipid metabolism). Cells also contain lipid bodies for eicosanoid production.
- Basophils and mast cells. Possess basophilic granules containing histamine, various proteases, glycosaminoglycans, peroxidase, and in mast cells, Charcot–Leyden protein. These are preformed factors that instantly trigger an immediate-type hypersensitivity reaction.
- NK cells (though belonging to the lymphoid lineage, their cytotoxic granules are mechanistically similar). Contain perforin, granzyme B, and granulysin to directly execute cytolysis.
Comparison of neutrophils and monocytes/macrophages
Although both groups of cells belong to professional phagocytes, their functional profiles differ radically. Neutrophils are optimally adapted for the early stages of an acute inflammatory response, whereas monocytes and macrophages operate on a long-term basis.
| Characteristic | Neutrophils | Monocytes and macrophages |
|---|---|---|
| Lifespan | Short (3–5 days) | Long (weeks, months) |
| Activation rate | Rapid (a matter of minutes) | Slow (takes hours) |
| Pinocytic capacity | Moderate | High |
| Membrane regeneration | Absent | Occurs |
| Phagosome reutilization | Impossible | Possible |
| Non-lysosomal secretion | Absent | Present |
In addition, the cells differ in Fc receptor expression. The FcγI receptor is present spontaneously on macrophages, whereas on neutrophils it appears only upon activation (resting cells possess only FcγII and FcγIII).
To remember the strict order of neutrophil granule activation, use the mnemonic: Secretory vesicles, Gelatinase, Specific, Azurophilic granules.
Class and exam questions
What markers distinguish azurophilic granules from others?
The main markers of primary (azurophilic) granules are the enzyme myeloperoxidase and the membrane molecule CD63.
Can neutrophils synthesize new granules to replace used ones?
No. Unlike macrophages, neutrophils are incapable of membrane regeneration, and their granular reserve is not restored following degranulation.
What is the function of gelatinase granules?
They secrete gelatinase, an enzyme that degrades extracellular matrix components. This enables neutrophils to cross basement membranes when migrating from blood into tissues.
Against which pathogens are neutrophil granule contents most effective?
Granule bactericidal factors demonstrate the highest efficacy against staphylococci, streptococci, and fungal pathogens, including species of the genus Candida.
What else to study on this topic
- Mechanism of the respiratory burst involving NADPH oxidase.
- Detailed composition of eosinophil specific granules and their role in extracellular cytolysis.
- Mechanism of action of perforin and granzyme B in NK cell cytotoxicity.
- The role of eosinophil lipid bodies in eicosanoid production and inflammation.
- Changes in the Fc receptor expression profile on the neutrophil membrane upon activation.
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