NEUTROPHILS: CHARACTERISTICS, MORPHOLOGY, FUNCTIONS, TYPES - BIOLOGY - 2025

The neutrophils are the leukocyte cell type and granulocyte subtype involved in the immune response engulfing bacteria, fungi and other potentially pathogenic entities for the organism.

Among the granular leukocytes, neutrophils are the most abundant cells, found in proportions between 65 and 75% of the total leukocyte count. This amount can increase if the body suffers from an infection.

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To fulfill its protective role, this cell exhibits a marked ability to move through tissues. They correspond to the first line of defense in the presence of an infection and are also related to inflammation events.

The nucleus of neutrophils is variable in terms of its morphology, which is why the cell is said to be polymorphonuclear. Generally, this nucleus has three to five irregular protrusions or lobes. The cytoplasm presents a series of granules that give it the characteristic pink color of this cell lineage.

characteristics

Generalities and classification of granulocytes

Blood is made up of various cellular elements. One of them are leukocytes or white blood cells, so called because of their lack of color when compared to erythrocytes or red blood cells.

Within the white blood cells there are several types, and one of them are granulocytes. They are so named since they present a large amount of granules in the cytoplasm. In turn, we have different types of granulocytes that differ from each other in response to different laboratory stains.

Granulocytes are eosinophils, with granules rich in basic proteins that are colored with acid dyes such as eosin; basophils, which present acidic granules and stain with basic dyes such as methylene blue; and neutrophils, which present both acidic and basic granules and present pink or lavender tones.

Neutrophil overview and classification

Within granulocytes, neutrophils are the most abundant cells. They are cells with a capacity for movement that are involved in the immune response and in the destruction of different pathogens and agents external to the body.

Mature neutrophils are characterized by a segmented nucleus. That is why some authors call these leukocytes polymorphonuclear cells, abbreviated PMNs, for their acronym in English.

Within the peripheral blood, we find two forms of neutrophils: one with a segmented nucleus and others with a band-shaped nucleus. In the circulation, most of these cells have a segmented nucleus.

Morphology

Dimensions

In the blood smears analyzed in the laboratory, it has been observed that the dimensions of the neutrophils are between 10 to 12 micrometers (µm), being slightly larger than the erythrocytes.

Core

One of the most prominent characteristics of neutrophils is the shape of their nucleus, with multiple lobes. Although granulocytes are classified according to their response to staining, they can be easily identified by this characteristic.

Young neutrophils exhibit a nucleus with a shape that resembles a band and does not yet present any type of lobes, it may be incipient.

When neutrophils have reached maturity, the nucleus can have several lobes - usually two to four. These lobes are linked by delicate strands of a nuclear nature.

The position of the lobes, and of the nucleus in general, is quite dynamic. Therefore, the lobes can vary in their position and also in number.

Chromatin

Relatively, the chromatin of neutrophils is quite condensed. The distribution of chromatin in neutrophils is characteristic of this cell lineage: heterochromatin (condensed chromatin with a low transcription rate) is located in large quantities at the edges of the nucleus, coming into contact with the nuclear envelope.

Euchromatin (relatively looser chromatin, with a generally high transcription rate) is located in the central region of the nucleus and there is very little of this chromatin that is in direct contact with the envelope.

In women, one of the sex X chromosomes is compacted and inactivated in a structure called Barr's corpuscle - this phenomenon occurs to compensate for genetic load. This is visualized as an appendix in one of the nuclear lobes.

Cytoplasm

Organelles and granules are found in the cytoplasm of neutrophils. Thanks to the immense number of granules, the neutrophil's cytoplasm acquires a pink or lilac coloration. In addition, there are significant amounts of glycogen. Below we will describe in detail each of the subcompartments of the cytoplasm:

Granules

As we mentioned, neutrophils are a type of granulocyte because their cytoplasm has different granules. In these leukocytes there are three types of granules: specific, azurophilic and tertiary.

Specific granules

The specific granules or secondary granules are small in size and quite abundant. Due to their small size they are difficult to visualize in the light microscope. However, in the light of electron microscopy the granules appear as ellipsoid structures. The density of the bodies is moderate.

Inside the specific granules we find type IV collagenase, phospholipidase, lactoferrin, vitamin B12 binding proteins, NADPH-oxidase, histaminase, receptors for the sheet, among others. There are also complement activators and other molecules with bactericidal properties.

Azurophilic granules

The azurophilic or primary granules are larger than the previous ones, but they are found in less quantity. They originate at the beginning of granulopoiesis and are present in all types of granulocytes. When the azure dye is applied to them, they acquire a purplish color. They are very dense bodies.

These bodies are analogous to lysosomes and contain hydrolases, elastases, cationic proteins, bactericidal proteins, and myeloperoxidase. The latter has the appearance of a substance with fine granules. This molecule contributes to the formation of hypochlorite and chloramines, substances that contribute to the elimination of bacteria.

An important component of azurophilic granules within the category of cationic proteins are the so-called defensins, which act in a similar way to an antibody.

Tertiary granules

In the last category we have tertiary granules. These are in turn divided into two types of granules, depending on the content: some are rich in phosphatases and the others in metalloproteins, such as gelatinases and collagenases. It is speculated that these proteins are able to contribute to the migration of the neutrophil through the connective tissue.

Organelles

In addition to the granules that are clearly visible in the cytoplasm of neutrophils, additional subcellular compartments are quite rare. However, in the center of the cell there is a nascent Golgi apparatus and a small number of mitochondria.

Features

Living in a world teeming with pathogenic single-celled organisms is a major challenge for multicellular organisms. In the course of evolution, cellular elements developed with the ability to engulf and destroy these potential threats. One of the main (and most primitive) barriers is formed by the innate immune system.

Neutrophils are part of this innate system. In the body, this system is responsible for the destruction of pathogens or molecules that are foreign to the body that are not specific to any antigen, relying on the barriers made up of the skin and mucous membranes.

In humans, the neutrophil count can exceed 70% of circulating leukocytes, being the first line of defense against a wide range of pathogens: from bacteria to parasites and fungi. Thus, among the functions of neutrophils we have:

Destruction of pathogenic entities

The main function of neutrophils is to destroy foreign molecules or materials that enter the body through phagocytosis - including microorganisms that could cause disease.

The process by which neutrophils destroy foreign entities consists of two steps: search through chemotaxis, cell motility, and diapédesis, followed by destruction thereof, through phagocytosis and digestion. This occurs as follows:

Step 1: chemotaxis

The recruitment of neutrophils generates an inflammatory process in the area where the binding with the leukocyte receptor occurred. Chemotactic agents can be produced by microorganisms, by cell damage, or by other types of leukocytes.

The first response of neutrophils is to reach the endothelial cells of the blood vessels through the use of adhesive-type molecules. Once the cells reach the site of infection or inflation, neutrophils begin the process of phagocytosis.

Step 2: phagocytosis

On the cell surface, neutrophils possess a wide variety of receptors with diverse functions: they can directly recognize the pathogenic organism, the apoptotic cell or any other particle, or they can recognize some opsonic molecule anchored to the foreign particle.

When a microorganism is "opsonized" it means that it is coated by antibodies, by complement or by both.

During the phagocytosis process, pseudopodia emerge from the neutrophil that begin to surround the particle to be digested. In this event, the phagosome formation occurs within the cytoplasm of the neutrophil.

Phagosome formation

The formation of the phagosome allows the NADH oxidase complex that is located inside this body to generate reactive oxygen species (such as hydrogen peroxide, for example) that end in the conversion to hypochlorite. Similarly, the different types of granules release bactericidal substances.

The combination of reactive oxygen species and bactericides allows the elimination of the pathogen.

Neutrophil death

After digestion of the pathogen takes place, the degradation product material can be stored in residual bodies or it can be disposed of by means of exocytosis. During this phenomenon, most of the participating neutrophils suffer from cell death.

What we know as “pus” is a thick whitish or yellowish exudate of dead bacteria mixed with neutrophils.

Recruitment of other cells

In addition to emptying the contents of the granules to attack pathogens, neutrophils are also responsible for secreting molecules into the extracellular matrix.

The molecules that are secreted to the outside act as chemotactic agents. That is, they are responsible for "calling" or "attracting" other cells, such as additional neutrophils, macrophages, and other inflammatory agents.

Generation of NETs

Neutrophils are cells that can generate what are known as extracellular neutrophil traps, abbreviated as NETs, ​​for its acronym in English.

These structures are generated after neutrophil death, as a result of antimicrobial activity. These extracellular structures are speculated to represent chains of nucleosomes.

In fact, the use of the term NETosis has been proposed to describe this particular form of cell death - which results in the release of NETs.

These structures have enzymes that we also find inside the granules of neutrophils, being capable of leading the destruction of bacterial agents, both gram negative and gram positive, or fungal agents.

Secretory function

Neutrophils have been associated with the secretion of substances of biological relevance. These cells are an important source of transcobalamin I, which is essential for the correct absorption of vitamin B12 in the body.

In addition, they are the source of an important variety of cytokines. Among these molecules, the production of interleukin-1, a substance that is known as a pyrogen, stands out. That is, a molecule capable of inducing fever processes.

Interleukin-1 is responsible for inducing the synthesis of other molecules called prostaglandins that act on the hypothalamus and cause the increase in temperature. Understanding it from this perspective, fever is a consequence of acute inflation resulting from the massive neutrophilic response.

Origin and development

How many neutrophils are produced?

Neutrophil production is estimated to be on the order of 10 ¹¹ cells per day, which can go up an order of magnitude when the body is experiencing a bacterial infection.

Where are neutrophils made?

Neutrophil development occurs in the bone marrow. Due to the importance of these cells and the significant number that must be produced, the bone marrow dedicates almost 60% of its total production to the origin of neutrophils.

How are neutrophils made?

The cell that originates them is called the granulocyte-monocyte progenitor, and as its name indicates, it is the cell that gives rise to both granulocytes and monocytes.

There are different molecules involved in the generation of neutrophils, but the main one is called granulocyte colony stimulating factor, and it is a cytokine.

In the bone marrow, there are three types of developing neutrophils: the stem cell group, the proliferating group, and the maturing group. The first group is made up of hematopoietic cells that are capable of renewal and differentiation.

The proliferation group is made up of cells in mitotic states (ie, in cell division) and includes myeloid progenitors, or colonies that form granulocytes, erythrocytes, monocytes, and megakaryocytes, granulocyte-macrophage progenitors, myeloblasts, promyelocytes, and myelocytes. The maturation stages occur in the order mentioned.

The last group consists of cells that are undergoing nuclear maturation and is made up of metamyelocytes and neutrophils - both banded and segmented.

How long do neutrophils last?

Compared to other cells of the immune system, neutrophils are considered to have a short half-life. Traditional estimates suggest that neutrophils last about 12 hours in circulation and a little over a day in tissues.

Today, methodologies and techniques that involve deuterium labeling are used. According to this approach, the half-life of neutrophils is increased up to 5 days. In the literature this discrepancy remains a matter of controversy.

Neutrophil migration

Within the three groups of neutrophils a cellular movement (of the neutrophils and their precursors) between the bone marrow, the peripheral blood and the tissues. In fact, one of the most relevant properties of this type of leukocyte is its ability to migrate.

As these are the most abundant white blood cells, they form the first wave of cells to reach the lesion. The presence of neutrophils (and also monocytes) implies a significant inflammatory reaction. Migration is under the control of certain adhesion molecules located on the cell surface that interact with endothelial cells.

Diseases

Neutrophilia

When the absolute neutrophil count exceeds 8.6.10 ⁹ the patient is considered to be experiencing neutrophilia. This condition is accompanied by granulocytic hyperplasia of the bone marrow, with the absence of eosinophilia, basophils, and erythrocytes with nuclei in the peripheral blood.

There are multiple causes that can lead to a benign increase in neutrophils, such as stress conditions, tachycardia events, fever, labor, excessive cardiovascular exercise, among others.

Causes associated with pathologies or conditions of medical relevance include inflammation, poisoning, hemorrhage, hemolysis and neoplasms.

Neutropenia

The opposite condition to neutrophilia is neutropenia. Causes associated with a drop in neutrophil levels include infections, physical agents such as X-rays, vitamin B12 deficiency, ingestion of medications, and the syndrome known as lazy white blood cell. The latter consists of random and directionless movements on the part of cells.

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