Neutrophils – What Are The Functions Of Neutrophils?
A disease causing microbe first meets the neutrophil. Neutrophil granulocytes are commonly called neutrophils. These are found in most abundance in the blood stream and are considered as very important in the immune system. The staining characteristics of the neutrophils on eosin and hematoxylin (H&E) is the reason behind the name ‘ Neutrophil’. A neutral pink neutrophils stain usually occurs after staining. The neutrophil nucleus is divided into two-five lobes.
More About Neutrophils
The lifetime of a neutrophil is shorter than the monocyte/macrophage phagocytes that live longer. Experts consider it as an evolutionary adaptation. Shorter lifetime of neutrophils help in minimizing the propagation of the phagocytes that are paracitized by pathogens. The more time those cells spend outside the host body, their destruction by the body defence system gets faster and easier. After digesting pathogens, the neutrophils are phagocytosed themselves by the macrophages. During this process PECAM-1 and phosphatidylserine are present on the surface of the cell.
Neutrophils are the first cells that move to the site of the inflammation during the beginning of the infection. They first move with the help of blood vessels, and then through the interstitial tissue. They follow the chemical signals from Interleukin-8 (IL-8) and C5a by the process called chemotaxis. The neutrophils appear to be the most dominant cells found in the pus. This is why the pus appears whitish/yellowish in their appearance.
The process of chemotaxis is responsible for the migration of the neutrophils towards the infection or inflammation site. The receptors present at the surface of the cell, help them detect the presence of chemical gradients of interferon gamma (IFN-gamma), interleukin-8 (IL-8) and C5a. These molecules are responsible for directing the path of migration.
How Are Neutrophils Measured?
- The average diameter of a neutrophil granulocyte is about 12-15 micrometers (µm).
- In humans, approximately 10^11 neutrophil granulocytes are produced each day. Hence they account for about 70% of the total white blood cells.
- The normal count has been found to be around 2.5-7.5 x 109/l. Neutrophils in a male can vary from those in a female.
- There is a minor difference, including the nucleus structure. The nucleus of the female cell would posses an extra X chromosome structure, known as a “neutrophil drumstick”.
Neutrophils are highly mobile, so then can aggregate quickly at the site of the infection. They get attracted by the cytokines. The cytokines are expressed with the help of activated endothelium, macrophages and mast cells. The neutrophils release cytokines to amplify the reactions in various other cell types. This is not the only role. It also is very important as a front-line defence system. Attacking the invading pathogens requires the presence of neutrophils. They follow three different kinds of strategies:
- phagocytosis (ingestion)
- generation of neutrophil extracellular traps (NETs)
- release of soluble anti-microbials (including granule proteins)
Phagocytes are nothing but neutrophils. They can ingest particles and microorganisms and kill them. Each event of the phagocytic attack results in the forming a phagosome. The reactive oxygen species is trapped within the phagosome along with the secreted hydrolytic enzymes. “Respiratory burst” occurs. When the oxygen is consumed during the process of generating reactive oxygen species, it is termed as “respiratory burst”.
Activation of the NADPH oxidase enzyme is involved. The NADPH oxidase can produce superoxide in large quantities, reactive oxygen species. The Superoxide gets dismutated by the catalytic reaction of the superoxide dismutases (MnSOD and Cu/ZnSOD) enzymes. Superoxide is converted into hydrogen peroxide due to the dismutation reaction, this is again converted to hypochlorous acid HClO with the help of green heme myeloperoxidase enzyme.
Neutrophils release a set of proteins with the help of Degranulation process. The release results in three different types of granules:
|1.||Specific Granules (Secondary Granules)||Cathelicidn and Lactoferrin|
|2.||Azurophilic Granules (Primary Granules)||Permeability increasing protein /bactericidal(BPI), myeloperoxidase, Defensins,cathepsin G and neutrophil elastase and serine proteases and|
|3.||Tertiary Granules||Gelatinase and Cathepsin|
NETs (Neutrophil Extracellular Traps)
Activation of neutrophils results in releasing DNA in the form of structures that look like a web. This can be a third mechanism of the defence system against the bacteria. These are named as the neutrophil extracellular traps. These are webs of fibers, composed of serine proteases and chromatin. These fiber traps help in killing and trapping microbes extracellularly.
The NETs provides antimicrobial components in high local concentration and they disarm, bind and kill the microbes without any dependence on the phagocytic uptake. NETs tend to serve as physical barriers that help in preventing the further spread of the pathogens.
Functions Of Neutrophils In Disease
Read the following functions of neutrophils in different diseases:
- Neutropenia denotes low neutrophil counts. This is more often a genetic disorder, but in few cases have been found to develop in later stages.
- For example, in case of some leukemic conditions or aplastic anemia. Sometimes medications, Chemotherapy, can also cause neutropenia.
- Sometimes, intracellular neutrophilic parasites cause colonization can also cause low neutrophil counts. After you suffer from Neutropenia, you get highly vulnerable to infections.
- Functional congenital disorders of neutrophils include chronic granulomatous disease which is a rare myeloperoxidase deficiency and a immune deficiency. These include the disorders of phagocytosis, deficiencies in the respiratory burst.
- When the neutrophil enzyme ‘elastase’ is not inhibited properly by the alpha 1-antitrypsin, it can lead to tissue damage due to inflammation. This condition is named as the alpha 1-antitrypsin deficiency.
- The pyrin gene or the marenstrin gene is expressed in the neutrophil granulocyte. Any mutation in this gene can lead to fever attacks, peritonitis, arthraligia eventually leading to amyloidosis. This causes the Familial Mediterranean fever (FMF).