THE FAST AND THE FURIOUS

Considering a title THE FAST AND THE FURIOUS reveals my interest towards movies but this one is not about movies but this one is about the first line of defense mechanism of our body THE NEUTROPHILS.
 They are fast enough in response to defend from initial infections and furious enough to be effective and hence my title.

WHAT IS THE ORIGIN OF THE TERM, NEUTROPHIL?

Neutrophil comes from the Latin word "neuter" meaning "neither," and the Greek word "philein" meaning "to love." Put the two words together and you have "love neither." This is a reference to the fact that neutrophils stain easy with neutral dyes. Dyes are colored stains that are used in laboratories, often to tell cells apart from one another. Neutral dyes are made up of salts that do not have an electric charge. This lack of an electric charge is why these dyes are called neutral.

WHAT ARE THESE CELLS:Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. In general, they are referred to as either neutrophils or polymorphonuclear neutrophils (or PMNs), and are subdivided into segmented neutrophils (or segs) and banded neutrophils (or bands). They form part of the polymorphonuclear cell family (PMNs) together with basophils and eosinophils.The name neutrophil derives from staining characteristics on hematoxylin and eosin (H&E) histological or cytological preparations.

STRUCTURE:A main characteristic of neutrophils is that they have three to five round sections within them called lobes that are connected by thin threads known as chromatin.Another characteristic of neutrophils is that their cytoplasm (a gel-like substance that fills up a cell) is light pink and mostly made of thin, difficult to see, pink or purplish-pink grain-like particles. The light pink cytoplasm provides a strong contrast with the dark colored nucleus.

WHERE ARE NEUTROPHILS MADE?

Neutrophils are made by the bone marrow (a tissue that fills the openings inside of bones). Neutrophils are sometimes made outside of the marrow as well. After the neutrophils are formed, they are released into the circulating blood.

WHAT PERCENT OF WHITE BLOOD CELLS ARE NEUTROPHILS?

Approximately 50% to 70% of white blood cells are neutrophils. Neutrophils are the most common type of white blood cell. The amount of neutrophils on blood work tests is known as the ANC (absolute neutrophil count). On most blood work tests, the ANC will be presented in terms of the amount of neutrophils per mm3 (cubic millimeters) of blood. See the next section for a description of cubic millimeters. The normal range for the neutrophil count is 1500 to 8000. It is important to keep in mind that the ranges mentioned above will be different depending on the machine used to do the blood test. Always use the normal range printed on the lab report to decide what range is normal.

Anti-microbial function

Being highly motile, neutrophils quickly congregate at a focus of infection, attracted by cytokines expressed by activated endothelium, mast cells, and macrophages. Neutrophils express  and release cytokines, which in turn amplify inflammatory reactions by several other cell types.

In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defence against invading pathogens. Neutrophils have three strategies for directly attacking micro-organisms: phagocytosis (ingestion), release of soluble anti-microbials (including granule proteins), and generation of neutrophil extracellular traps (NETs)

Phagocytosis

Neutrophils are phagocytes, capable of ingesting microorganisms or particles. For targets to be recognised, they must be coated in opsonins—a process known as antibody opsonization. They can internalize and kill many microbes, each phagocytic event resulting in the formation of a phagosome into which reactive oxygen species and hydrolytic enzymes are secreted. The consumption of oxygen during the generation of reactive oxygen species has been termed the "respiratory burst", although unrelated to respiration or energy production.

The respiratory burst involves the activation of the enzyme NADPH oxidase, which produces large quantities of superoxide, a reactive oxygen species. Superoxide dismutates, spontaneously or through catalysis via enzymes known as superoxide dismutases (Cu/ZnSOD and MnSOD), to hydrogen peroxide, which is then converted to hypochlorous acid HClO, by the green heme enzyme myeloperoxidase. It is thought that the bactericidal properties of HClO are enough to kill bacteria phagocytosed by the neutrophil, but this may instead be a step necessary for the activation of proteases.

DEGRANULATION: Four kinds of granules exist in neutrophils that display differences in content and regulation. Secretory vesicles are the most likely to release their contents by degranulation, followed by gelatinase granules, specific granules, and azurophil granules.

WHAT CAN CAUSE THE LEVEL OF NEUTROPHILS TO BE TOO HIGH?

There are many possible causes for an abnormally high neutrophil count. A neutrophil level that is more than 8000 is considered to be abnormally high. One basic cause of a high neutrophil count is when a high level of stress is placed on the body. The stress can due to many factors such as nervousness, exercise, or seizures (involuntary muscle movements due to overexcitement of nerve cells in the brain). Another cause is a sudden infection from bacteria. Damage or inflammation of tissues can also lead to a high neutrophil count. Examples would be burn injuries and a heart attack.

Sudden kidney failure can cause a high neutrophil count. The kidneys are two organs located on each side of the spine, behind the stomach. The kidneys filter (remove) wastes from the blood. A condition known as ketoacidosis can also cause a high neutrophil count. Ketoacidosis is a condition in which acids and poisonous chemical substances known as ketones are produced by the body. Ketones are produced when the body has a difficult time breaking down fats.

Another cause of a high neutrophil count is eclampsia. Eclampsia is a rare, but serious complication of pregnancy characterized by an attack of convulsions (abnormal, severe, involuntary muscle movements) . 

A high neutrophil count can be caused by cancer spreading in the body. Cancer is a group of diseases in which symptoms are due to an abnormal and excessive growth of cells in one of the body organs or tissues.

Hemolytic anemia can cause a high neutrophil count. Hemolytic anemia is a condition in which the red blood cells are destroyed earlier than they should be. Red blood cells help carry oxygen to the blood. Another cause of a high neutrophil count is polycythemia vera. Polycythemia vera is a condition of unknown cause in which there is a long-term increase in red blood cells and other types of cells. Myeloid metaplasia can cause a high neutrophil count. Myeloid metaplasia is a condition in which bone marrow (a tissue that fills the openings of bones) grows in abnormal places in the body.

Certain medications can also lead to a high neutrophil count. One such medication is corticosteroids. Corticosteroids are a group of drugs that act similarly to a natural chemical in the body known as corticosteroid hormone. Corticosteroid hormones control the body's use of nutrients and the amount of water and salts in the urine (pee). Another such medication that can raise the neutrophil count is lithium carbonate. Lithium carbonate is a type of salt that is used as a drug to reduces mania (an abnormal, overly excited state).

WHAT CAN CAUSE THE LEVEL OF NEUTROPHILS TO BE TOO LOW?

There are many possible causes for an abnormally low neutrophil count. When the number of neutrophils are abnormally low (less than 1500), this condition is known as neutropenia. Neutropenia can be caused by a decreased production of neutrophils. A decreased production of neutrophils can be caused by leukemia. Leukemia is a type of cancer in the blood in which bone marrow (a tissue that fills the openings of bones) is replaced by early forms of white blood cells. See the previous section for a description of cancer.

In leukemia, the level of neutrophil production decreases because they are crowded out of the bone marrow by the early forms of white blood cells. A condition that occurs before leukemia, known as preleukemia, can also cause an abnormal decrease in neutrophils. Another cause of a decreased neutrophil count is myelofibrosis, in which the normal bone marrow is replaced by fibrous tissue (the connective tissue of the body).

Another cause of decreased neutrophil production is damage to the bone marrow. Such damage can be caused by infections, medications, and radiation (a type of energy often used to treat cancer). Bone marrow destruction occurs in aplastic anemia. Aplastic anemia is a condition in which the there is an abnormal decrease in the cells that make up blood (such as white blood cells) because the bone marrow is not working properly to make these cells.

Besides decreased neutrophil production, another cause of a decreased neutrophil count is an increase in the destruction of neutrophils. Such destruction can be caused by a severe bacterial infection that causes the formation of pus or leads to bacteria increasing in the blood. Pus is a yellow or green creamy substance sometimes found at the site of infections.

The body can actually produce proteins known as antineutrophil antibodies that destroy neutrophils. These proteins are produced in autoimmune diseases in which the body mistakenly attacks itself. An example of an autoimmune disorder that can cause an abnormal decrease in neutrophils is systemic lupus erythematosus (abbreviated SLE). SLE is a long-term disease in which the connective tissues throughout the body are inflamed because the body's defense system attacks these tissues as if they were foreign substances.

Another condition that can cause a decrease in neutrophils is hypersplenism. Hypersplenism is a condition in which there is an abnormal enlargement of the spleen and an abnormal decrease in white blood cells. The spleen is an organ near the stomach that helps fight infection and removes and destroys worn-out red blood cells. In a condition known as Felty's syndrome, an abnormal decrease in neutrophils is found. Felty's syndrome is a group of abnormal changes (such as an enlarged spleen, frequent infections, and a decreased white blood cell count) that accompanies rheumatoid arthritis. Rheumatoid arthritis is another example of an immune disorder (see last paragraph) in which the body's defense system attacks its own tissues, causing inflammation of bone joints.

Certain medications can cause an abnormal decrease in the neutrophil account. One such type of medication are phenothiazines drugs, which are used to treat psychosis, allergies, and vomiting. Psychosis is a mental disorder characterize by an impairment in the ability to understand reality. Another type of drug that can cause an abnormally low neutrophil count is phenylbutazone, which is a drug used to reduce inflammation in conditions such as arthritis (inflammation of bone joints).

Another cause of a low neutrophil count is too little vitamin B12 or folic acid (a type of vitamin) in the body. A vitamin is one of a group of substances made up partly of carbon (an element) that are essential in small amounts for normal bodily functioning and chemical processes in the body to take place.

Cardipolumonary bypass can lead to low neutrophil count. Cardiopulmonary bypass is a procedure used during heart surgery in which the flow of blood is moved away from the heart and the lungs with a pump and returned to the aorta. The aorta is the largest artery of the body. An artery is a blood vessel that carries blood away from the heart.

Dialysis can cause a low neutrophil count as well. Dialysis is a technique in which one is hooked up to a machine that performs the functions of the kidneys, removing wastes and extra water from the blood. The kidneys are two organs located on each side of the spine, behind the stomach. The kidneys filter (remove) wastes from the blood.

A rare cause of a decreased neutrophil count is Chediak-Higashi syndrome. This is a disorder found at birth characterized by a massive decrease in white blood cells, movement abnormalities, pale skin, a pale appearance in the back of the eye, an abnormal sensitivity to light, reoccurring infections, and early death.