Granulocyte

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Granulocyte
1907 Granular Leukocytes.jpg
Types of granulocytes
Details
System Immune system
Identifiers
MeSH D006098
FMA 62854
Anatomical terms of microanatomy

Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. [1] Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that is, they have varying shapes (morphology) of the nucleus (segmented, irregular; often lobed into three segments); and are referred to as polymorphonuclear leukocytes (PMN, PML, or PMNL). In common terms, polymorphonuclear granulocyte refers specifically to "neutrophil granulocytes", [2] the most abundant of the granulocytes; the other types (eosinophils, basophils, and mast cells) have varying morphology. Granulocytes are produced via granulopoiesis in the bone marrow.

Contents

Types

There are four types of granulocytes (full name polymorphonuclear granulocytes): [3]

Except for the mast cells, their names are derived from their staining characteristics; for example, the most abundant granulocyte is the neutrophil granulocyte, which has neutrally staining cytoplasmic granules. [4]

Neutrophils

A neutrophil with a segmented nucleus (center and surrounded by erythrocytes), the intra-cellular granules are visible in the cytoplasm (Giemsa-stained high magnification) Neutrophil2.jpg
A neutrophil with a segmented nucleus (center and surrounded by erythrocytes), the intra-cellular granules are visible in the cytoplasm (Giemsa-stained high magnification)

Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, constituting 60% to 65% of the total circulating white blood cells, [5] and consisting of two subpopulations: neutrophil-killers and neutrophil-cagers. One litre of human blood contains about five billion (5x109) neutrophils, [6] which are about 12–15 micrometres in diameter. [7] Once neutrophils have received the appropriate signals, it takes them about thirty minutes to leave the blood and reach the site of an infection. [8] Neutrophils do not return to the blood; they turn into pus cells and die. [8] Mature neutrophils are smaller than monocytes, and have a segmented nucleus with several sections(two to five segments); each section is connected by chromatin filaments. Neutrophils do not normally exit the bone marrow until maturity, but during an infection neutrophil precursors called myelocytes and promyelocytes are released. [9]

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). [10] Neutrophils are professional phagocytes: [11] they are ferocious eaters and rapidly engulf invaders coated with antibodies and complement, as well as damaged cells or cellular debris. The intracellular granules of the human neutrophil have long been recognized for their protein-destroying and bactericidal properties. [12] Neutrophils can secrete products that stimulate monocytes and macrophages; these secretions increase phagocytosis and the formation of reactive oxygen compounds involved in intracellular killing. [13]

Neutrophils have two types of granules; primary (azurophilic) granules (found in young cells) and secondary (specific) 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 (used to generate toxic bacteria-killing substances). [14] In addition, secretions from the primary granules of neutrophils stimulate the phagocytosis of IgG antibody-coated bacteria. [15] The secondary granules contain compounds that are involved in the formation of toxic oxygen compounds, lysozyme, and lactoferrin (used to take essential iron from bacteria). [14] Neutrophil extracellular traps (NETs) comprise a web of fibers composed of chromatin and serine proteases 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. [16]

Eosinophils

Eosinophils also have kidney-shaped lobed nuclei (two to four lobes). The number of granules in an eosinophil can vary because they have a tendency to degranulate while in the blood stream. [17] 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 [14] ); [18] receptors that bind to IgG and IgA are used to help with this task. [19] These cells also have a limited ability to participate in phagocytosis, [20] they are professional antigen-presenting cells, they regulate other immune cell functions (e.g., CD4+ T cell, dendritic cell, B cell, mast cell, neutrophil, and basophil functions), [21] they are involved in the destruction of tumor cells, [17] and they promote the repair of damaged tissue. [22] A polypeptide called interleukin-5 interacts with eosinophils and causes them to grow and differentiate; this polypeptide is produced by basophils and by T-helper 2 cells (TH2). [18]

Basophils

Basophils are one of the least abundant cells in bone marrow and blood (occurring at less than two percent of all cells). Like neutrophils and eosinophils, they have lobed nuclei; however, they have only two lobes, and the chromatin filaments that connect them are not very visible. Basophils have receptors that can bind to IgE, IgG, complement, and histamine. The cytoplasm of basophils contains a varied amount of granules; these granules are usually numerous enough to partially conceal the nucleus. Granule contents of basophils are abundant with histamine, heparin, chondroitin sulfate, peroxidase, platelet-activating factor, and other substances. [23]

When an infection occurs, mature basophils will be released from the bone marrow and travel to the site of infection. [24] When basophils are injured, they will release histamine, which 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 migration to the site of infection so that they can consume microbes. [20]

Mast cells

Mast cells are a type of granulocyte that are present in tissues; [3] they mediate host defense against pathogens (e.g., parasites) and allergic reactions, particularly anaphylaxis. [3] Mast cells are also involved in mediating inflammation and autoimmunity as well as mediating and regulating neuroimmune system responses, [3] [25] [26] it release histamine

Development

Granulocytes are derived from stem cells residing in the bone marrow. The differentiation of these stem cells from multipotent hematopoietic stem cell into granulocytes is termed granulopoiesis. Multiple intermediate cell types exist in this differentiation process, including myeloblasts and promyelocytes. [27]

Function

Granule contents

Examples of toxic materials produced or released by degranulation by granulocytes on the ingestion of microorganisms are:

Clinical significance

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 agranulocytosis (etymologically, "no granulocytes at all"; clinically, granulocyte levels less than 5% of normal) and neutropenia (deficiency of neutrophil granulocytes). Granulocytes live only one to two days in circulation (four days in spleen or other tissue), so transfusion 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 suffering from type 1 diabetes mellitus.

Research suggests giving granulocyte transfusions to prevent infections decreased the number of people who had a bacterial or fungal infection in the blood. [28] Further research suggests participants receiving therapeutic granulocyte transfusions show no difference in clinical reversal of concurrent infection. [29]

Additional images

See also

Related Research Articles

<span class="mw-page-title-main">Phagocytosis</span> Cell membrane engulfing a large particle

Phagocytosis is the process by which a cell uses its plasma membrane to engulf a large particle, giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is called a phagocyte.

<span class="mw-page-title-main">Eosinophil</span> Variety of white blood cells

Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells and basophils, they also control mechanisms associated with allergy and asthma. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply.

<span class="mw-page-title-main">CD32</span> Surface receptor glycoprotein

CD32, also known as FcγRII or FCGR2, is a surface receptor glycoprotein belonging to the Ig gene superfamily. CD32 can be found on the surface of a variety of immune cells. CD32 has a low-affinity for the Fc region of IgG antibodies in monomeric form, but high affinity for IgG immune complexes. CD32 has two major functions: cellular response regulation, and the uptake of immune complexes. Cellular responses regulated by CD32 include phagocytosis, cytokine stimulation, and endocytic transport. Dysregulated CD32 is associated with different forms of autoimmunity, including systemic lupus erythematosus. In humans, there are three major CD32 subtypes: CD32A, CD32B, and CD32C. While CD32A and CD32C are involved in activating cellular responses, CD32B is inhibitory.

<span class="mw-page-title-main">Mast cell</span> Cell found in connective tissue

A mast cell is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems. Mast cells were discovered by Paul Ehrlich in 1877. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and vascular permeability in brain tumors.

<span class="mw-page-title-main">Neutrophil</span> Type of white blood cell

Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different animals. They are also known as neutrocytes, heterophils or polymorphonuclear leukocytes.

<span class="mw-page-title-main">Basophil</span> Type of white blood cell

Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. They are the largest type of granulocyte. They are responsible for inflammatory reactions during immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. They also produce compounds that coordinate immune responses, including histamine and serotonin that induce inflammation, and heparin that prevents blood clotting, although there are less than that found in mast cell granules. Mast cells were once thought to be basophils that migrated from the blood into their resident tissues, but they are now known to be different types of cells.

<span class="mw-page-title-main">Phagocyte</span> Cells that ingest harmful matter within the body

Phagocytes are 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 essential for fighting infections and for subsequent immunity. Phagocytes are important throughout the animal kingdom and are highly developed within vertebrates. One litre of human blood contains about six billion phagocytes. They were discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae. Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery. Phagocytes occur in many species; some amoebae behave like macrophage phagocytes, which suggests that phagocytes appeared early in the evolution of life.

Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed by phagocytes. Different types of things ("targets") can be tagged by opsonins for phagocytosis, including: pathogens, cancer cells, aged cells, dead or dying cells, excess synapses, or protein aggregates. Opsonins help clear pathogens, as well as dead, dying and diseased cells.

<span class="mw-page-title-main">Agranulocyte</span> One of the two types of white blood cells

In immunology, agranulocytes are one of the two types of leukocytes, the other type being granulocytes. Agranular cells are noted by the absence of granules in their cytoplasm, which distinguishes them from granulocytes. Leukocytes are the first level of protection against disease. The two types of agranulocytes in the blood circulation are lymphocytes and monocytes. These make up about 35% of the hematologic blood values.

<span class="mw-page-title-main">Phagosome</span> Vesicle formed around a particle engulfed by a phagocyte via phagocytosis

In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs).

A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round nucleus. These cells consist of lymphocytes and monocytes, whereas erythrocytes and platelets have no nuclei, and granulocytes have multi-lobed nuclei. In humans, lymphocytes make up the majority of the PBMC population, followed by monocytes, and only a small percentage of dendritic cells.

<span class="mw-page-title-main">Innate immune system</span> Immunity strategy in living beings

The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, prokaryotes, and invertebrates.

<span class="mw-page-title-main">Fc receptor</span> Surface protein important to the immune system

In immunology, an Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.

<span class="mw-page-title-main">Promyelocyte</span> Granulocyte precursor cell

A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte. Promyelocytes measure 12–20 microns in diameter. The nucleus of a promyelocyte is approximately the same size as a myeloblast but their cytoplasm is much more abundant. They also have less prominent nucleoli than myeloblasts and their chromatin is more coarse and clumped. The cytoplasm is basophilic and contains primary red/purple granules.

<span class="mw-page-title-main">Granulopoiesis</span> Formation of granulocyte cells in the bone marrow

Granulopoiesis is a part of haematopoiesis, that leads to the production of granulocytes. A granulocyte, also referred to as a polymorphonuclear leukocyte (PMN), is a type of white blood cell that has multi lobed nuclei, usually containing three lobes, and has a significant amount of cytoplasmic granules within the cell. Granulopoiesis takes place in the bone marrow. It leads to the production of three types of mature granulocytes: neutrophils, eosinophils and basophils.

<span class="mw-page-title-main">Degranulation</span> Process by which cells lose secretory granules

Degranulation is a cellular process that releases antimicrobial, cytotoxic, or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including granulocytes. It is also used by certain lymphocytes such as natural killer (NK) cells and cytotoxic T cells, whose main purpose is to destroy invading microorganisms.

A non-specific immune cell is an immune cell that responds to many antigens, not just one antigen. Non-specific immune cells function in the first line of defense against infection or injury. The innate immune system is always present at the site of infection and ready to fight the bacteria; it can also be referred to as the "natural" immune system. The cells of the innate immune system do not have specific responses and respond to each foreign invader using the same mechanism.

In hematology, myelopoiesis in the broadest sense of the term is the production of bone marrow and of all cells that arise from it, namely, all blood cells. In a narrower sense, myelopoiesis also refers specifically to the regulated formation of myeloid leukocytes (myelocytes), including eosinophilic granulocytes, basophilic granulocytes, neutrophilic granulocytes, and monocytes.

<span class="mw-page-title-main">White blood cell</span> Type of cells of the immunological system

White blood cells, also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells include three main subtypes: granulocytes, lymphocytes and monocytes.

Neutrophil oxidative burst test is a measure of neutrophil oxidation and is a useful assay in the diagnosis of chronic granulomatous disease and is also a useful means to determine the overall metabolic integrity of phagocytosing neutrophils. The NADPH oxidase enzyme is missing in CGD. From total blood, neutrophils can be purified and the NADPH oxidase activity can be measured with different methods in these cells after activation. Phagocytosis by polymorphonuclear neutrophils and monocytes constitutes an essential arm of host defense against bacterial or fungal infections. The phagocytic process can be separated into several major stages: chemotaxis, attachment of particles to the cell surface of phagocytes, ingestion (phagocytosis) and intracellular killing by oxygen-dependent and oxygen-independent mechanisms.

References

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  2. ↑ WebMD (2009). "leukocyte, polymorphonuclear". Webster's New World Medical Dictionary (3rd ed.). Houghton Mifflin Harcourt. p. 244. ISBN   978-0-544-18897-6.
  3. 1 2 3 4 Breedveld A, Groot Kormelink T, van Egmond M, de Jong EC (October 2017). "Granulocytes as modulators of dendritic cell function". Journal of Leukocyte Biology. 102 (4): 1003–16. doi: 10.1189/jlb.4MR0217-048RR . PMID   28642280.
  4. ↑ Wittekind D (1979). "On the nature of Romanowsky dyes and the Romanowsky-Giemsa effect". Clin Lab Haematol. 1 (4): 247–62. doi:10.1111/j.1365-2257.1979.tb01090.x. PMID   94558.
  5. ↑ Stvrtinová, Viera; Ján Jakubovský and Ivan Hulín (1995). "Neutrophils, central cells in acute inflammation". Inflammation and Fever from Pathophysiology: Principles of Disease. Computing Centre, Slovak Academy of Sciences: Academic Electronic Press. ISBN   80-967366-1-2. Archived from the original on December 31, 2010. Retrieved March 28, 2009.
  6. ↑ Hoffbrand, Pettit & Moss 2005 , p. 331
  7. ↑ Abbas, Chapter 12, 5th Edition[ full citation needed ][ page needed ]
  8. 1 2 Sompayrac 2008 , p. 18
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  11. ↑ Robinson & Babcock 1998 , p. 187
    Ernst & Stendahl 2006 , pp. 7–10
  12. ↑ Paoletti, Notario & Ricevuti 1997 , p. 62
  13. ↑ Soehnlein O, Kenne E, Rotzius P, Eriksson EE, Lindbom L (January 2008). "Neutrophil secretion products regulate anti-bacterial activity in monocytes and macrophages". Clinical and Experimental Immunology. 151 (1): 139–45. doi:10.1111/j.1365-2249.2007.03532.x. PMC   2276935 . PMID   17991288.
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  15. ↑ Soehnlein O, Kai-Larsen Y, Frithiof R, Sorensen OE, Kenne E, Scharffetter-Kochanek K, et al. (October 2008). "Neutrophil primary granule proteins HBP and HNP1-3 boost bacterial phagocytosis by human and murine macrophages". The Journal of Clinical Investigation. 118 (10): 3491–502. doi:10.1172/JCI35740. PMC   2532980 . PMID   18787642.
  16. ↑ Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, et al. (April 2007). "Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood". Nature Medicine. 13 (4): 463–9. doi:10.1038/nm1565. PMID   17384648. S2CID   22372863.
  17. 1 2 Hess CE. "Segmented Eosinophil". University of Virginia Health System. Archived from the original on 2009-08-13. Retrieved 2009-04-10.
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  19. ↑ Kelly D. Stone; Calman Prussin; Dean D. Metcalfe (February 2010). "IgE, Mast Cells, Basophils, and Eosinophils". Allergy and Clincical Immunology. 125 (2): S73-80. doi:10.1016/j.jaci.2009.11.017. PMC   2847274 . PMID   20176269.
  20. 1 2 Campbell & Reece 2002 , p. 903
  21. ↑ Akuthota P, Wang HB, Spencer LA, Weller PF (August 2008). "Immunoregulatory roles of eosinophils: a new look at a familiar cell". Clinical and Experimental Allergy. 38 (8): 1254–63. doi:10.1111/j.1365-2222.2008.03037.x. PMC   2735457 . PMID   18727793.
  22. ↑ Kariyawasam HH, Robinson DS (April 2006). "The eosinophil: the cell and its weapons, the cytokines, its locations". Seminars in Respiratory and Critical Care Medicine. 27 (2): 117–27. doi:10.1055/s-2006-939514. PMID   16612762.
  23. ↑ Hellman L, Akula S, Fu Z, Wernersson S (2022). "Mast Cell and Basophil Granule Proteases — In Vivo Targets and Function". Front Immunol. 13: 918305. doi: 10.3389/fimmu.2022.918305 . PMC   9294451 . PMID   35865537.
  24. ↑ Hess CE. "Mature Basophil". University of Virginia Health System. Archived from the original on 2009-08-13. Retrieved 2009-04-10.
  25. ↑ Lee DM, Friend DS, Gurish MF, Benoist C, Mathis D, Brenner MB (September 2002). "Mast cells: a cellular link between autoantibodies and inflammatory arthritis". Science. 297 (5587): 1689–92. Bibcode:2002Sci...297.1689L. doi:10.1126/science.1073176. PMID   12215644. S2CID   38504601.
  26. ↑ Polyzoidis S, Koletsa T, Panagiotidou S, Ashkan K, Theoharides TC (September 2015). "Mast cells in meningiomas and brain inflammation". Journal of Neuroinflammation. 12 (1): 170. doi: 10.1186/s12974-015-0388-3 . PMC   4573939 . PMID   26377554. MCs originate from a bone marrow progenitor and subsequently develop different phenotype characteristics locally in tissues. Their range of functions is wide and includes participation in allergic reactions, innate and adaptive immunity, inflammation, and autoimmunity [34]. In the human brain, MCs can be located in various areas, such as the pituitary stalk, the pineal gland, the area postrema, the choroid plexus, thalamus, hypothalamus, and the median eminence [35]. In the meninges, they are found within the dural layer in association with vessels and terminals of meningeal nociceptors [36]. MCs have a distinct feature compared to other hematopoietic cells in that they reside in the brain [37]. MCs contain numerous granules and secrete an abundance of prestored mediators such as corticotropin-releasing hormone (CRH), neurotensin (NT), substance P (SP), tryptase, chymase, vasoactive intestinal peptide (VIP), vascular endothelial growth factor (VEGF), TNF, prostaglandins, leukotrienes, and varieties of chemokines and cytokines some of which are known to disrupt the integrity of the blood-brain barrier (BBB) [38–40].

    They key role of MCs in inflammation [34] and in the disruption of the BBB [41–43] suggests areas of importance for novel therapy research. Increasing evidence also indicates that MCs participate in neuroinflammation directly [44–46] and through microglia stimulation [47], contributing to the pathogenesis of such conditions such as headaches, [48] autism [49], and chronic fatigue syndrome [50]. In fact, a recent review indicated that peripheral inflammatory stimuli can cause microglia activation [51], thus possibly involving MCs outside the brain.
  27. ↑ Calzetti F, Finotti G, Cassatella MA (March 2023). "Current knowledge on the early stages of human neutropoiesis". Immunol Rev. 314 (1): 111–124. doi:10.1111/imr.13177. PMID   36484356.
  28. ↑ Estcourt LJ, Stanworth S, Doree C, Blanco P, Hopewell S, Trivella M, Massey E (June 2015). "Granulocyte transfusions for preventing infections in people with neutropenia or neutrophil dysfunction". The Cochrane Database of Systematic Reviews. 2018 (6): CD005341. doi:10.1002/14651858.cd005341.pub3. PMC   4538863 . PMID   26118415.
  29. ↑ Estcourt LJ, Stanworth SJ, Hopewell S, Doree C, Trivella M, Massey E (April 2016). "Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction". The Cochrane Database of Systematic Reviews. 4 (7): CD005339. doi:10.1002/14651858.cd005339.pub2. PMC   4930145 . PMID   27128488.

Bibliography

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