White blood cells (WBCs)/Neutrophils and Neupogen

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White Blood Cells - Normal levels:

The normal range for WBC count is 4,300 to 10,800 cells per cubic millimeter (cmm) or 4.3 to 10.8 x 109 cells per liter. A range of 11 to 17 x 109/L may be considered mild to moderate leukocytosis, and a range of 3.0 to 5.0x109/L may be considered mild leukopenia.

http://ibdcrohns.about.com/od/diagnostictesting/p/testwbc.htm

Normal Results

4,500-10,000 white blood cells per microliter (mcL). (4.5-10.0)

Note: Normal value ranges may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results.

http://www.nlm.nih.gov/medlineplus/ency/article/003643.htm

Normal values for total WBC and differential in adult males and females are:

Total WBC: 4,500 - 10,000

Bands or stabs: 3 - 5 %

Granulocytes (or polymorphonuclears)

Neutrophils (or segs): 50 - 70% relative value (2500-7000 absolute value)

Eosinophils: 1 - 3% relative value (100-300 absolute value)

Basophils: 0.4% - 1% relative value (40-100 absolute value)

Agranulocytes (or mononuclears)

Lymphocytes: 25 - 35% relative value (1700-3500 absolute value)

Moncytes: 4 - 6% relative value (200-600 absolute value)

Each differential always adds up to 100%. To make an accurate assessment, consider both relative and absolute values. For example a relative value of 70% neutrophils may seem within normal limits; however, if the total WBC is 20,000, the absolute value (70% x 20,000) would be an abnormally high count of 14,000.

http://www.rnceus.com/cbc/cbcwbc.html

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Neupogen can sometimes be RX'd if your white blood cells get low on treatment. You can read about Neupogen at this link:

http://www.rxlist.com/neupogen-drug.htm

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http://en.wikipedia.org/wiki/White_blood_cell (Click on link for pictures)

White blood cells (WBCs), or leukocytes (also spelled "leucocytes"), are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five[1] different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a hematopoietic stem cell. Leukocytes are found throughout the body, including the blood and lymphatic system.[2]

The number of WBCs in the blood is often an indicator of disease. There are normally between 4×109 and 1.1×1010 white blood cells in a litre of blood, making up approximately 1% of blood in a healthy adult.[3] An increase in the number of leukocytes over the upper limits is called leukocytosis, and a decrease below the lower limit is called leukopenia. The physical properties of leukocytes, such as volume, conductivity, and granularity, may change due to activation, the presence of immature cells, or the presence of malignant leukocytes in leukemia.

The name "white blood cell" derives from the fact that after centrifugation of a blood sample, the white cells are found in the buffy coat, a thin, typically white layer of nucleated cells between the sedimented red blood cells and the blood plasma. The scientific term leukocyte directly reflects this description, derived from Greek leukos (white), and kytos (cell). Blood plasma may sometimes be green if there are large amounts of neutrophils in the sample, due to the heme-containing enzyme myeloperoxidase that they produce.

There are several different types of white blood cells. They all have many things in common, but are all distinct in form and function. A major distinguishing feature of some leukocytes is the presence of granules; white blood cells are often characterized as granulocytes or agranulocytes:

Granulocytes (polymorphonuclear leukocytes): leukocytes characterised by the presence of differently staining granules in their cytoplasm when viewed under light microscopy. These granules are membrane-bound enzymes which primarily act in the digestion of endocytosed particles. There are three types of granulocytes: neutrophils, basophils, and eosinophils, which are named according to their staining properties. Agranulocytes (mononuclear leucocytes): leukocytes characterized by the apparent absence of granules in their cytoplasm. Although the name implies a lack of granules these cells do contain non-specific azurophilic granules, which are lysosomes[4]. The cells include lymphocytes, monocytes, and macrophages.[5]

Neutrophil

Main article: Neutrophil granulocyte

Neutrophils defend against bacterial or fungal infection and other very small inflammatory processes that are usually first responders to microbial infection; their activity and death in large numbers forms pus. They are commonly referred to as polymorphonuclear (PMN) leukocytes, although technically PMN refers to all granulocytes. They have a multilobed nucleus which may appear like multiple nuclei, hence the name polymorphonuclear leukocyte. The cytoplasm may look transparent because of fine granules that are pale lilac. Neutrophils are very active in phagocytosing bacteria and are present in large amount in the pus of wounds. These cells are not able to renew their lysosomes used in digesting microbes and die after having phagocytosed a few pathogens. [citation needed] Most common cell seen in acute inflammation, come in and kill foreign substance.

[edit] Eosinophil

Main article: Eosinophil granulocyte

Eosinophils primarily deal with parasitic infections and an increase in them may indicate such. Eosinophils are also the predominant inflammatory cells in allergic reactions. The most important causes of eosinophilia include allergies such as asthma, hay fever, and hives; and also parasitic infections. Generally their nucleus is bi-lobed. The cytoplasm is full of granules which assume a characteristic pink-orange color with eosin stain.

[edit] Basophil

Main article: Basophil granulocyte

Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing inflammation. The nucleus is bi- or tri-lobed, but it is hard to see because of the number of coarse granules which hide it. They are characterized by their large blue granules.

[edit] Lymphocyte

Main article: Lymphocyte

Lymphocytes are much more common in the lymphatic system. Lymphocytes are distinguished by having a deeply staining nucleus which may be eccentric in location, and a relatively small amount of cytoplasm. The blood has three types of lymphocytes:

B cells: B cells make antibodies that bind to pathogens to enable their destruction. (B cells not only make antibodies that bind to pathogens, but after an attack, some B cells will retain the ability to produce an antibody to serve as a 'memory' system.) T cells:

CD4+ (helper) T cells co-ordinate the immune response and are important in the defense against intracellular bacteria. In acute HIV infection, these T cells are the main index to identify the individual's immune system activity. Research has shown [9] that CD8+ cells are also another index to identify human's immune activity. CD8+ cytotoxic T cells are able to kill virus-infected and tumor cells. γδ T cells possess an alternative T cell receptor as opposed to CD4+ and CD8+ αβ T cells and share characteristics of helper T cells, cytotoxic T cells and natural killer cells.

Natural killer cells: Natural killer cells are able to kill cells of the body which are displaying a signal to kill them, as they have been infected by a virus or have become cancerous.

[edit] Monocyte

Main article: Monocyte

Monocytes share the "vacuum cleaner" (phagocytosis) function of neutrophils, but are much longer lived as they have an additional role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed, or so that an antibody response may be mounted. Monocytes eventually leave the bloodstream to become tissue macrophages which remove dead cell debris as well as attacking microorganisms. Neither of these can be dealt with effectively by the neutrophils. Unlike neutrophils, monocytes are able to replace their lysosomal contents and are thought to have a much longer active life. They have the kidney shaped nucleus and are typically agranulated. They also possess abundant cytoplasm.

Once monocytes move from the bloodstream out into the body tissues, they undergo changes (differentiate) allowing phagocytosis and are then known as macrophages.

[edit] Medication causing leukopenia

Some medications can have an impact on the number and function of white blood cells. Leukopenia is the reduction in the number of white blood cells, which may affect the overall white cell count or one of the specific populations of white blood cells. For example, if the number of neutrophils is low, the condition is known as neutropenia. Likewise, low lymphocyte levels are termed lymphopenia. Medications which can cause leukopenia include clozapine, an antipsychotic medication with a rare adverse effect leading to the total absence of all granulocytes (neutrophils, basophils, eosinophils). Other medications include immunosuppressive drugs, such as sirolimus, mycophenolate mofetil, tacrolimus, and cyclosporine. Interferons used to treat multiple sclerosis, like Rebif, Avonex, and Betaseron, can also cause leukopenia.

[edit] Fixed leukocytes

Some leukocytes migrate into the tissues of the body to take up a permanent residence at that location rather than remaining in the blood. Often these cells have specific names depending upon which tissue they settle in, such as fixed macrophages in the liver which become known as Kupffer cells. These cells still serve a role in the immune system.

Histiocytes Dendritic cells (Although these will often migrate to local lymph nodes upon ingesting antigens) Mast cells Microglia

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http://en.wikipedia.org/wiki/Neutrophil_granulocyte

Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They form part of the polymorphonuclear cell family (PMNs) together with basophils and eosinophils [1] [2].[3])

The name, neutrophil, derives from staining characteristics on hematoxylin and eosin (H & E) histological or cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinophilic white blood cells stain bright red, neutrophils stain a neutral pink. Normally neutrophils contain a nucleus divided into 2-5 lobes.

Neutrophils are normally found in the blood stream. However, during the beginning (acute) phase of inflammation, particularly as a result of bacterial infection and some cancers[4][5], neutrophils are one of the first-responders of inflammatory cells to migrate toward the site of inflammation, firstly through the blood vessels, then through interstitial tissue, following chemical signals (such as Interleukin-8 (IL-8) and C5a) in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance.

Neutrophils are recruited to the site of injury within minutes following trauma and are the hallmark of acute inflammation.[6]

Neutrophil granulocytes have an average diameter of 12-15 micrometers (µm) in peripheral blood smears.

With the eosinophil and the basophil, they form the class of polymorphonuclear cells, named for the nucleus's characteristic multilobulated shape (as compared to lymphocytes and monocytes, the other types of white cells). Neutrophils are the most abundant white blood cells in humans (approximately 10^11 are produced daily) ; they account for approximately 70% of all white blood cells (leukocytes).

The stated normal range for human blood counts varies between laboratories, but a neutrophil count of 2.5-7.5 x 109/L is a standard normal range. People of African and Middle Eastern descent may have lower counts, which are still normal.

A report may divide neutrophils into segmented neutrophils and bands.

A minor difference is found between the neutrophils from a male subject and a female subject. The cell nucleus of a neutrophil from a female subject shows a small additional X chromosome structure, known as a "neutrophil drumstick".

[edit] Life Span

The average half-life of non-activated neutrophils in the circulation is about 12 hours. Upon activation, they marginate (position themselves adjacent to the blood vessel endothelium), and undergo selectin-dependent capture followed by integrin-dependent adhesion in most cases, after which they migrate into tissues, where they survive for 1–2 days.

Neutrophils are much more numerous than the longer-lived monocyte/macrophage phagocytes. A pathogen (disease-causing microorganism or virus) is likely to first encounter a neutrophil. Some experts hypothesize that the short lifetime of neutrophils is an evolutionary adaptation. The short lifetime of neutrophils minimizes propagation of those pathogens that parasitize phagocytes because the more time such parasites spend outside a host cell, the more likely they will be destroyed by some component of the body's defenses. Also, because neutrophil antimicrobial products can also damage host tissues, their short life limits damage to the host during inflammation.[citation needed]

Neutrophils will often be phagocytosed themselves by macrophages after digestion of pathogens. PECAM-1 and phosphatidylserine on the cell surface are involved in this process.

[edit] Chemotaxis

Neutrophils undergo a process called chemotaxis, which allows them to migrate toward sites of infection or inflammation. Cell surface receptors allow neutrophils to detect chemical gradients of molecules such as interleukin-8 (IL-8), interferon gamma (IFN-gamma), and C5a, which these cells use to direct the path of their migration.

[edit] 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[7] 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) [8].

[edit] Phagocytosis

Neutrophils are phagocytes, capable of ingesting microorganisms or particles. 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 step necessary for the activation of proteases.[9].

[edit] Degranulation

Neutrophils also release an assortment of proteins in three types of granules by a process called degranulation:

Granule type

Protein

specific granules (or "secondary granules")

Lactoferrin and Cathelicidin

azurophilic granules (or "primary granules")

myeloperoxidase, bactericidal/permeability increasing protein (BPI), Defensins and the serine proteases neutrophil elastase and cathepsin G

tertiary granules

cathepsin and gelatinase

[edit] Neutrophil Extracellular Traps(NETs)

Zychlinsky and colleagues recently described a new striking observation that activation of neutrophils causes the release of web-like structures of DNA; this represents a third mechanism for killing bacteria.[10] These neutrophil extracellular traps (NETs) comprise a web of fibers composed of chromatin and serine proteases that trap and kill microbes extracellularly. It is suggested that NETs provide a high local concentration of antimicrobial components and bind, disarm, and kill microbes independent of phagocytic uptake. In addition to their possible antimicrobial properties, NETs may serve as a physical barrier that prevents further spread of pathogens. Trapping of bacteria may be a particularly important role for NETs in sepsis, where NET are formed within blood vessels.[11] Recently, NETs have been shown to play a role in inflammatory diseases, as NETs could be detected in preeclampsia, a pregnancy related inflammatory disorder in which neutrophils are known to be activated.[12]

[edit] Role in disease

Low neutrophil counts are termed neutropenia. This can be congenital (genetic disorder) or it can develop later, as in the case of aplastic anemia or some kinds of leukemia. It can also be a side-effect of medication, most prominently chemotherapy. Neutropenia makes an individual highly susceptible to infections. Neutropenia can be the result of colonization by intracellular neutrophilic parasites.

Functional disorders of neutrophils are often hereditary. They are disorders of phagocytosis or deficiencies in the respiratory burst (as in chronic granulomatous disease, a rare immune deficiency, and myeloperoxidase deficiency).

In alpha 1-antitrypsin deficiency, the important neutrophil enzyme elastase is not adequately inhibited by alpha 1-antitrypsin, leading to excessive tissue damage in the presence of inflammation - most prominently pulmonary emphysema.

In Familial Mediterranean fever (FMF), a mutation in the pyrin (or marenostrin) gene, which is expressed mainly in neutrophil granulocytes, leads to a constitutively active acute phase response and causes attacks of fever, arthralgia, peritonitis, and - eventually - amyloidosis.[13]

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