Morphological features and biosynthesis
Mature neutrophils have an average diameter of 9 to 12 µm. Their main distinguishing feature is a segmented nucleus, which most commonly consists of three segments. The chromatin inside the nucleus is very densely packed as inactive heterochromatin. The cytoplasm is rich in specific neutral granules, which gave this cell type its name.
Due to the tight packing of nuclear material, the promoter regions required for the binding of differentiation factors become inaccessible. This severely limits gene expression and the synthesis of new macromolecules de novo. Nevertheless, despite such pronounced structural limitations of chromatin, the cells still retain the capacity for biosynthesis, albeit on a very limited scale.
Life span and migration into tissues
During migration, neutrophils are distributed unevenly. The bulk of the cells settle in the liver and bone marrow. A significant portion (about 20%) is sequestered in the pulmonary microvasculature, and another approximately 15% heads to the spleen.
The direction of their movement is set by specific chemotactic factors, primarily leukotriene B4 and interleukin-8 (IL-8), which are produced in small quantities in tissues. The migration process itself across the vascular wall requires adhesion molecules (such as β2-integrins, P-selectins, and E-selectins), as well as the enzyme elastase, which is secreted by the migrating cells themselves.
In tissues, neutrophils function for a short time—only 3–5 days. After this, they die via spontaneous apoptosis (programmed cell death). To prevent the release of toxic enzymes and damage to surrounding healthy tissues, the dead cells are rapidly phagocytosed by resident macrophages. Modern immunology also suggests that a small fraction of tissue neutrophils may transform into long-lived forms or even differentiate into macrophages, although the exact function of such tissue cells remains fully unclear so far.
Membrane phenotype
Surface markers of neutrophils are studied using flow cytometry. The membrane of these cells displays a rich arsenal of molecules:
- CD13 (aminopeptidase N) functions as a receptor for a number of viruses.
- CD14 is a receptor for binding bacterial lipopolysaccharide (LPS), although it is present on neutrophils in significantly lower amounts than on monocytes.
- β2-integrins (LFA-1, Mac-1, p150/95) mediate adhesion processes.
- Fc receptors are represented by FcγRII (CD32) and FcγRIII (CD16) forms.
- Complement receptors—CR1, CR3, and CR4 are present on the surface.
Of particular importance are receptors responsible for perceiving chemotactic signals: C3aR, C5aR, the leukotriene B4 receptor, as well as CXCR1 and CXCR2 (receptors for the main chemoattractant IL-8). In addition, CXCR4 is expressed, which is a receptor for the SDF-1 factor that is responsible for cell retention and binding to tissues. Development and activation are regulated by receptors for G-CSF, IL-17, and IL-23.
Molecules of the major histocompatibility complex class I (MHC-I) are present on the membrane constitutively, i.e., continuously. At the same time, MHC-II molecules appear only upon stimulation by specific cytokines, primarily under the action of GM-CSF.
Toll-like receptors
Neutrophils possess a wide spectrum of Toll-like receptors (TLRs), which distinguishes them from other myeloid lineage cells.
| Molecule group | Neutrophils | Eosinophils | Monocytes |
|---|---|---|---|
| Toll-like receptors (TLRs) | TLR-1, 2, 4, 5, 6, 7, 8, 9, 10 | TLR-1, 4, 7, 10 | TLR-1, 2, 3, 4, 5, 6, 7, 8, 9, 10 |
As can be seen from the table, neutrophils express almost all types of TLRs, with the exception of TLR-3, which is characteristic only of monocytes.
Briefly: answers to topical questions
What enzymes and proteins are contained in specific (secondary) granules of neutrophils?
Specific (secondary) granules of neutrophils contain enzymes and proteins that are active at neutral and slightly alkaline pH values. These include:
- Lactoferrin is a competitive protein that binds substances vital for pathogens.
- Alkaline phosphatase is an enzyme involved in the early stages of degranulation.
- Lysozyme is a cationic protein with enzymatic activity.
- BPI protein is a vitamin B12-binding factor.
- NADPH oxidase—a key enzyme catalyzing the "respiratory burst" and the generation of reactive oxygen species.
What CD markers are characteristic of the neutrophil membrane phenotype?
The neutrophil membrane phenotype is characterized by the expression of a number of surface CD markers. The main molecules include:
- CD13 (aminopeptidase N) is a receptor for a number of viruses.
- CD14 is a receptor for lipopolysaccharide, present in smaller amounts than on monocytes.
- CD16 (FcγRIII) is an Fc receptor.
- CD32 (FcγRII) is an Fc receptor.
What morphological stages of maturation does a neutrophil pass through in the bone marrow?
During maturation in the bone marrow, a neutrophil sequentially passes through six main morphological stages. The traditional myeloid maturation series includes:
- Myeloblasts
- Promyelocytes
- Myelocytes
- Metamyelocytes (juvenile forms)
- Band cells (stab cells)
- Segmented neutrophils (mature forms)
Normally, only the last two stages of maturation are present in the bloodstream, whereas the appearance of earlier forms (metamyelocytes, myelocytes, promyelocytes) indicates the stimulation of leukopoiesis in pathology.
What mechanisms of intracellular bacterial killing do neutrophils use?
For intracellular bacterial killing within phagolysosomes, neutrophils use a complex of bactericidal factors. The main mechanisms include:
- Oxygen-dependent factors—generation of reactive oxygen species as a result of the "respiratory burst" involving NADPH oxidase.
- Myeloperoxidase microbicidal system—participation of myeloperoxidase, hydrogen peroxide, and halide ions with the formation of microbicidal compounds, including hypochlorous acid.
- Oxygen- and nitric oxide-independent factors—local acidification of the phagolysosomal environment down to pH 4.5–5.0 due to V-ATPase.
- Enzymatic cleavage—action of acid hydrolases and neutral proteases (serprocidins).
- Cationic proteins and bactericidal peptides—lysozyme, lactoferrin, BPI proteins, defensins, and cathelicidins.
Class and exam questions
How long do neutrophils live in tissues?
Their duration of stay in tissues ranges from 3 to 5 days, after which they undergo spontaneous apoptosis.
Why do neutrophils synthesize virtually no new proteins?
Due to the high chromatin (heterochromatin) density, promoter regions of genes become inaccessible to transcription factors, which sharply reduces the scale of de novo biosynthesis.
Do neutrophils always express MHC-II molecules?
No, MHC-II molecules are not permanently present on their surface. Their expression is induced only under the influence of specific cytokines, primarily GM-CSF.
What else to study on this topic
- Mechanisms of IL-8 receptor binding via CXCR1 and CXCR2
- The role of elastase in migration across the endothelium
- Differences in Toll-like receptor expression among myeloid cells
- The process of phagocytosis of apoptotic neutrophils by macrophages
- Effect of GM-CSF on neutrophil phenotype changes
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