Granulocyte
Encyclopedia
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five 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...
s characterized by the presence of granule
Granule (cell biology)
In cell biology, a granule is a small particle. It can be any structure barely visible by light microscopy. The term is most often used to describe a secretory vesicle.-Leukocytes:...
s in their cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
. They are also called polymorphonuclear leukocytes (PMN or PML) because of the varying shapes of the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, which is usually lobed into three segments. In common parlance, the term polymorphonuclear leukocyte often refers specifically to neutrophil granulocyte
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
s, the most abundant of the granulocytes. Granulocytes or PMN are released from the bone marrow by the regulatory complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
proteins.
Types of granulocytes
There are three types of granulocytes, distinguished by their appearance under Wright's stainWright's stain
Wright's stain is a histologic stain that facilitates the differentiation of blood cell types. It is used primarily to stain peripheral blood smears and bone marrow aspirates which are examined under a light microscope...
:
- Neutrophil granulocyteNeutrophil granulocyteNeutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
s - Eosinophil granulocyteEosinophil granulocyteEosinophil granulocytes, usually called eosinophils or eosinophiles , are white blood cells that are one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells, they also control mechanisms associated with...
s - Basophil granulocyteBasophil granulocyteBasophil granulocytes, sometimes referred to as basophils, are the least common of the granulocytes, representing about 0.01% to 0.3% of circulating white blood cells....
s
Their names are derived from their staining
Staining (biology)
Staining is an auxiliary technique used in microscopy to enhance contrast in the microscopic image. Stains and dyes are frequently used in biology and medicine to highlight structures in biological tissues for viewing, often with the aid of different microscopes...
characteristics; for example, the most abundant granulocyte is the neutrophil granulocyte
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
, which has neutrally staining cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
ic granules.
Other white blood cells which are not granulocytes ("agranulocyte
Agranulocyte
Agranulocytes are a category of white blood cells characterised by the absence of granules in their cytoplasm.There are two types of agranulocytes:* Lymphocytes* Monocytes....
s") are mainly lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s and monocyte
Monocyte
Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s.
Neutrophils
Circulatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
and are the most abundant type of phagocyte, constituting 50% to 60% of the total circulating white blood cells. One litre of human blood contains about five billion neutrophils 5x109, which are about 12-15 micrometer
Micrometer
A micrometer , sometimes known as a micrometer screw gauge, is a device incorporating a calibrated screw used widely for precise measurement of small distances in mechanical engineering and machining as well as most mechanical trades, along with other metrological instruments such as dial, vernier,...
s in diameter, and live approximately 6 hours. Once neutrophils have received the appropriate signals, it takes them about thirty minutes to leave the blood and reach the site of an infection. Neutrophils do not return to the blood; they turn into pus
Pus
Pus is a viscous exudate, typically whitish-yellow, yellow, or yellow-brown, formed at the site of inflammatory during infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collection of pus within or beneath the epidermis is known as a pustule or...
cells and die. Mature neutrophils are smaller than monocytes, and have a segmented nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
with several sections(two to five segments); each section is connected by chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
filaments. Neutrophils do not normally exit the bone marrow until maturity but during an infection neutrophil precursors called myelocyte
Myelocyte
A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow, but not in circulating blood .-Histology:...
s and promyelocyte
Promyelocyte
A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte.-External links: - "18. Bone Marrow and Hemopoiesis: bone marrow smear, promyelocyte and erythroblasts " "Bone marrow" "Bone marrow"* - "Bone marrow smear"...
s are released.
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
Neutrophil extracellular traps
Neutrophil extracellular traps are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens....
(NETs).
Neutrophils are professional phagocytes: they are ferocious eaters and rapidly engulf invaders coated with antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
and complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
, and damaged cells or cellular debris. The intra-cellular granules of the human neutrophil have long been recognized for their protein-destroying and bactericidal properties. Neutrophils can secrete products that stimulate monocytes and macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s; these secretions increase phagocytosis and the formation of reactive oxygen compounds involved in intracellular killing. Neutrophils have two types of granules; primary (azurophilic) granules (found in young cells) and specific granules
Specific granules
Specific granules are secretory vesicles found exclusively in cells of the immune system called granulocytes. They are also known as secondary granules....
(which are found in more mature cells). Primary granules contain cationic proteins and defensins that are used to kill bacteria, proteolytic enzymes and cathepsin G to break down (bacterial) proteins, lysozyme to break down bacterial cell walls, and myeloperoxidase
Myeloperoxidase
Myeloperoxidase is a peroxidase enzyme that in humans is encoded by the MPO gene. Myeloperoxidase is most abundantly expressed in neutrophil granulocytes . It is a lysosomal protein stored in azurophilic granules of the neutrophil...
(use to generate toxic bacteria-killing substances). In addition, secretions from the primary granules of neutrophils stimulate the phagocytosis of IgG antibody-coated bacteria. The secondary granules contain compounds that are involved in the formation of toxic oxygen compounds, lysozyme, and lactoferrin
Lactoferrin
Lactoferrin , also known as lactotransferrin , is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions...
(used to take essential iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
from bacteria). Neutrophil extracellular traps
Neutrophil extracellular traps
Neutrophil extracellular traps are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens....
(NETs) comprise a web of fibers composed of chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
and serine protease
Serine protease
Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
s that trap and kill microbes extracellularly. Trapping of bacteria is a particularly important role for NETs in sepsis, where NET are formed within blood vessels.
Eosinophils
Degranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
while in the blood stream. Eosinophils play a crucial part in the killing of parasites (e.g. enteric nematodes) because their granules contain a unique, toxic basic protein and cationic protein (e.g. cathepsin
Cathepsin
Cathepsins are proteases: proteins that break apart other proteins, found in many types of cells including those in all animals. There are approximately a dozen members of this family, which are distinguished by their structure, catalytic mechanism, and which proteins they cleave...
); receptors that bind to IgE
IGE
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...
are used to help with this task. These cells also have a limited ability to participate in phagocytosis, they are professional antigen presenting cells, they regulate other immune cell functions (e.g. CD4+ T cell, dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
, B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
, mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
, neutrophil, and basophil functions), they are involved in the destruction of tumor cells, and they promote the repair of damaged tissue. A polypeptide called interleukin-5 interacts with eosinophils and causes them to grow and differentiate; this polypeptide is produced by basophils.
Basophils
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
and blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
(occurring at less than two percent of all cells). Like neutrophils and eosinophils they have lobed nuclei
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
; however they only have two lobes and the chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
filaments that connect them are not very visible. Basophils have receptors that can bind to IgE
IGE
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...
, IgG, complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
, and histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
. The cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
of basophils contains a varied amount of granules; these granules are usually numerous enough to partially conceal the nucleus. Granule
Granule
Granule is a generic term used for a small particle or grain. The generic term is employed in a variety of specific contexts.* Granule , visible structures in the photosphere of the Sun arising from activity in the Sun's convective zone...
contents of basophils are abundant with histamine, heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
, chondroitin sulfate
Chondroitin sulfate
Chondroitin sulfate is a sulfated glycosaminoglycan composed of a chain of alternating sugars . It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities...
, peroxidase
Peroxidase
Peroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...
, platelet activating factor, and other substances.
When an infection occurs mature basophils will be released from the bone marrow and travel to the site of infection. When basophils are injured they will release histamine; this contributes to the inflammatory response that helps fight invading organisms. Histamine causes dilation and increased permeability of capillaries close to the basophil. Injured basophils and other leukocytes will release another substance called prostaglandins that contributes to an increased blood flow to the site of infection. Both of these mechanisms allow blood clotting elements to be delivered to the infected area (this begins the recovery process and blocks the travel of microbes to other parts of the body). Increased permeability of the inflamed tissue also allows for more phagocyte
Phagocyte
Phagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...
migration to the site of infection so that they can consume microbes.
Granulopoiesis: the Genesis of Granulocytes
Granulocytes are derived from stem cells residing in the bone marrow. The differentiation of these stem cells from pluripotent hematopoietic stem cell into granulocytes is termed granulopoiesisGranulopoiesis
Granulopoiesis is hematopoiesis of granulocytes.It occurs primarily within bone marrow and involves the following stages:* Pluripotential hemopoietic stem cell* Myeloblast* Promyelocyte* Eosino/neutro/basophilic myelocyte...
. Multiple intermediate cell types exist in this differentiation process, and these include myeloblasts and promyelocyte
Promyelocyte
A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte.-External links: - "18. Bone Marrow and Hemopoiesis: bone marrow smear, promyelocyte and erythroblasts " "Bone marrow" "Bone marrow"* - "Bone marrow smear"...
s.
Toxic materials produced or released
Examples of toxic materials produced or released by degranulationDegranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
by granulocytes on the ingestion of microorganism includes:
- Low pH vesiclesVesicle (biology)A vesicle is a bubble of liquid within another liquid, a supramolecular assembly made up of many different molecules. More technically, a vesicle is a small membrane-enclosed sack that can store or transport substances. Vesicles can form naturally because of the properties of lipid membranes , or...
(3.5-4.0) - Toxic oxygenOxygenOxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
-derived products (e.g. superoxideSuperoxideA superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...
, hydrogen peroxideHydrogen peroxideHydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
, hydroxyHydroxylA hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
radicals, singlet oxygen, hypohaliteHypohaliteA hypohalite is an oxyanion containing a halogen in oxidation state +1.This includes hypoiodite, hypobromite, hypochlorite, and hypofluorite....
) - Toxic nitrogenNitrogenNitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
oxides (nitric oxideNitric oxideNitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
) - AntimicrobialAntimicrobialAn anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...
agents (DefensinDefensinDefensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates. They have also been reported in plants. They are, and function as, host defense peptides. They are active against bacteria, fungi and many enveloped and nonenveloped viruses. They consist of 18-45 amino...
s and Eosinophil cationic proteinEosinophil cationic proteinEosinophil Cationic Protein also known as ribonuclease 3 is a basic protein located in the eosinophil primary matrix. In humans, the eosinophil cationic protein is encoded by the RNASE3 gene.ECP is released during degranulation of eosinophils...
) - EnzymeEnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s- LysozymeLysozymeLysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases, enzymes that damage bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between...
: dissolves cell walls of some gram positive bacteria - Acid hydrolaseAcid hydrolaseAn acid hydrolase is an enzyme that works best at acidic pHs. It is commonly located in lysosomes, which are acidic on the inside. Acid hydrolases may be nucleases, proteases, glycosidases, lipases, phosphatases, sulfatases and phospholipases and make up the approximately 50 degradative enzymes of...
s: further digest bacteria
- Lysozyme
Pathology
Granulocytopenia is an abnormally low concentration of granulocytes in the blood. This condition reduces the body's resistance to many infections. Closely related terms include agranulocytosisAgranulocytosis
Granulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
(no granulocytes at all) and neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
(deficiency of neutrophil granulocyte
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
s). Granulocytes live only ~10 hours in circulation (for days in spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
or other tissue), so transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
of granulocytes as a therapeutic strategy would confer a very short-lasting benefit. In addition, there are many complications associated with such a procedure.
There is usually a granulocyte chemotactic defect in individuals who suffer from insulin dependent diabetes mellitus.
See also
- Blood countBlood Count"Blood Count" is a 1967 jazz composition by Billy Strayhorn. It was originally meant for a three-piece work Strayhorn was writing for Duke Ellington and initially titled "Blue Cloud". However, Strayhorn was hospitalized in 1967 due to cancer and finished the composition while in the hospital. He...
- White blood cellWhite blood cellWhite blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five 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...
- Immune systemImmune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
- Innate immune systemInnate immune systemThe innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
- HaematopoiesisHaematopoiesisHaematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells...
- TrogocytosisTrogocytosisTrogocytosis is a process whereby lymphocytes conjugated to antigen-presenting cells extract surface molecules from these cells and express them on their own surface...