General Description
The production of neutrophils takes place
in the bone marrow. Once the release of these cells into the blood
stream is concrete, they are destined for the sector of the body where
their intervention would be necessary.
It is important to
mention that neutrophils are the white blood cells (also called
leukocytes) of greater presence in the blood of people. Indeed, 70% of
an individual's white blood cells can be neutrophils.
White
blood cells or leukocytes are a type of blood cell whose function is to
defend the body against infections, pathogens and tumor cells.
There are several types of leukocytes: lymphocytes, monocytes, eosinophils, basophils and neutrophils.
What are neutrophils?
Neutrophils are the most abundant type of leukocytes or white blood cells.
They
are characterized by the multilobulated form of their nucleus and for
helping in the first place to the points of acute inflammation in
response to the signals that produce damaged cells and cells of the
immune system. In this way, neutrophils constitute a large proportion of
the early cellular infiltrate in tissues with inflammation, being the
largest component of the purulent exudate.
Neutrophils
constitute the first line of defense against invading microorganisms.
They use strategies such as phagocytosis of pathogens and the release of
antimicrobial factors.
It is also a type of cell capable of stimulating the response of other immune cells.
The
participation of neutrophils makes it possible to create an
antimicrobial environment in the place where inflammation has occurred,
which contributes to the death of pathogens.
Valuation of neutrophils
From
a blood analysis or complete blood count, it is possible to estimate
the number of different cells that make up the blood. It is a very
useful test in case of clinical situations of infection and chronic
illnesses.
Functions and types
Among the actions
carried out by neutrophils is the segregation of enzymes that allow the
destruction of pathogenic microorganisms. Neutrophils can even
phagocytose the microbes that are causing the infection.
If the
organism needs a very high quantity of neutrophils before a bacterial
infection, numerous immature neutrophils are generated that receive the
name of cayados. These neutrophils, which are also called en band,
remain in the bone marrow as a reserve.
On the other hand,
segmented neutrophils are found, and the mature ones are the ones that
are most abundant in the blood. Its function consists of transferring to
the fabrics to fight against the action of the germs.
Particular features
The
nucleus of neutrophils presents segmented chromatin in different lobes,
although this segmentation does not appear in stray neutrophils. The
cytoplasm, on the other hand, has many lytic enzymes.
It should
be noted that neutrophils cannot be stained with basic or acidic dyes:
this property derives its name. Under a microscope these leukocytes
appear with a pale pinkish hue.
Normal and abnormal values
Normal
neutrophil values are around 2,000-7,500/mL, representing 45-75% of
total leukocytes. Aunque in analytical studies we can study their
absolute number, it is frequent to study their relative number in
relation to the rest of blood cell count.
Age is the determining
factor for the number of neutrophils that must be found in the blood.
Note that these two values are not directly proportional; for example:
understood as quantity per microliter of blood, babies have between
4000 and 14 000, 10-year-old children have between 1400 and 6000 and
adults between 1500 and 7000.
If the count gives a value that exceeds the normal maximum, if there is neutrophilia, it will take place in cases of:
*
infections: in particular caused by bacteria, although they can also be
the cause of parasites and viruses, such as pneumonia or appendicitis;
* non-infectious chronic inflammations: rheumatic fever or arthritis, among others;
* emotional and physical origin: excessive exercise, stress, smoking, strokes or embarrassment;
* drugs: generally corticosteroids;
* blood cancer: chronic granulocytic (or myelogenous) leukemia, which causes an increase in white blood cells in the medulla.
When
a low count of neutrophils is obtained in a laboratory analysis, the
patient suffers from neutropenia. This disorder is due to one of the
following causes:
* infections: among the most common ones are
infantile viral infections (chickenpox, rubeola, measles), viral
hepatitis and bacterial infections (tuberculosis, brucellosis);
*
congenital diseases: Kostmann syndrome, cyclic neutropenia, Schwachman
Diamond syndrome, benign chronic neutropenia, Chediak Higashi syndrome;
* chemotherapy: chlorambucil, cyclophosphamide;
* blood problems: aplastic anemia.
Determining factors
The
number of neutrophils in the blood can be affected by different
factors, as well as we have seen until now. With regard to drugs, in
addition to the already mentioned corticosteroids, we must add
antipsychotics and lithium, all with the same consequence: an increase
in normal values.
With regard to the decrease, we have talked
about chemotherapy, but clozapine, methimazole, rituximab and
procainamide can also be produced. Of course, these medications are not
indicated arbitrarily, but they have very specific functions: we are
talking about antipsychotics, antibiotics, antithyroids and
antiarrhythmics, products that many times save the life of the patient.
For this reason, the solution is not as simple as eliminating them from
the treatment.
High neutrophils
The
increase in the number of neutrophils, also known as neutrophilia, can
happen due to several situations, the main ones being:
*Infections; *Inflammatory disorders;
*Diabetes;
*Uremia;
*Eclampsia in pregnancy;
*Hepatic necrosis;
*Chronic myeloid leukemia;
*Myeloproliferative syndromes;
*Bleeding;
*Burn;
*Electric shock;
*Cancer.
Neutrophilia
can also happen due to physiological conditions, such as in newborns,
during childbirth, after episodes of repeated vomiting, fear, stress,
use of drugs with adrenaline, anxiety and after excessive physical
activity. Thus, if the neutrophil count is high, the doctor may order
other diagnostic tests to correctly identify the cause and initiate the
appropriate treatment. See more about neutrophilia.
Low neutrophils
A decrease in the number of neutrophils, also called neutropenia, can happen due to:
*Aplastic, megaloblastic or iron deficiency anemia; *Leukemia;
*Hypothyroidism;
*Use of medications;
*Autoimmune diseases such as Systemic Lupus Erythematosus;
*myelofibrosis;
*Cirrhosis.
In
addition, there may be neonatal neutropenia in case of severe viral or
bacterial infection after birth. Children with Down syndrome also tend
to have low neutrophils without any health problems.
Representation of neutrophils
Neutrophils have a characteristic multilobed nucleus. Chemotaxis agents that attract neutrophils to sites of infection include:
Protein fragments released when complement is activated (eg, C5a);
Factors derived from the fibrinolytic and kinin systems;
Products of other leukocytes and platelets;
Products of certain bacteria.
Neutrophils have a large arsenal of enzymes and antimicrobial proteins stored in two main types of granules:
The
primary granules (azurophils) are lysosomes that contain acid
hydrolases, myeloperoxidase and muramidase (lysozyme); they also contain
antimicrobial proteins, including defensins, seprocidins, cetelicidins
and bacterial permeability-inducing protein (BPI)
and Secondary granules (specific for neutrophils) contain lactoferrin and lysozyme.
During
phagocytosis, lysosomes containing antimicrobial proteins fuse with
vacuoles containing ingested microorganisms (called phagosomes), forming
phagolysosomes, where destruction of the organisms occurs.
Neutrophils
also release granules and cytotoxic substances into the extracellular
environment when they are activated by immune complexes (antibodies
linked to their specific antigens) through their Fc receptors. This is
an important example of collaboration between the natural and acquired
immune systems, being an important mechanism in immune complex diseases
(type III hypersensitivity).
Development of neutrophils
Monocytes
and neutrophils develop from a common precursor cell, the
CFU-granulocyte macrophage (CFU-GM) cell. Myelopoiesis (the development
of myeloid cells) begins in the liver of the human fetus around the 6th
week of gestation.
CFU-GMs mature under the influence of
colony-stimulating factors (CSFs) and various interleukins. These
factors, which are relevant for the upregulation of hematopoiesis, are:
Derived
primarily from stromal cells (connective tissue cells) in the bone
marrow; They are also produced by mature forms of differentiated myeloid
and lymphoid cells.
Neutrophil expression
The
undifferentiated hematopoietic stem cell marker, CD34, like other early
markers of this lineage, does not exist on neutrophils and mature
mononuclear phagocytic cells. Other markers can also be lost during
differentiation in one way, but maintained in another.
For
example, the common precursor of monocytes and neutrophils, the UFC-GM
cell, expresses major histocompatibility complex (MHC) II molecules, but
only monocytes continue to express significant levels of this marker.
It
is important to point out that CFU-GM go through different stages of
differentiation until they become neutrophils. As CFU-GM differentiates
in the neutrophil pathway, we can distinguish several distinct
morphological stages. Myeloblasts differentiate into promyelocytes and
myelocytes, which mature and are released into the circulation as
neutrophils.
The unique pathway of differentiation of CFU-GM in
mature neutrophils results from the acquisition of specific receptors
for growth and differentiation factors in progressive stages of their
development. Differentiation surface markers disappear or are expressed
in cells as they develop into granulocytes. For example, class II MHC
molecules are found in GM-CFU, but there are no mature neutrophils.
It
is difficult to assess the functional activity of the different stages
of granulocyte development, however it is most likely that only when the
cells are mature is their functional potential fulfilled.
There
is some evidence that neutrophil activity, as measured by phagocytosis
and chemotaxis, is lower in fetal life than in adult life. However, this
may be partially due to lower levels of opsonins in fetal serum and not
due to cell characteristics.