Anaphylatoxin
Encyclopedia
Anaphylatoxins, or anaphylotoxins, are fragments ( C3a
, C4a
and C5a
) that are produced as part of the activation of the complement system
.. Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defense. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments. A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins.: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability. They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals. The proteins are highly hydrophilic, with a mainly alpha-helical structure held together by 3 disulphide bridges.
(release of substances) of endothelial cells, mast cells or phagocytes, which produce a local inflammatory response. If the degranulation is widespread, it can cause a shock-like syndrome similar to that of an allergic reaction.
Anaphylatoxins indirectly mediate:
, codeine
, synthetic ACTH) and some neurotransmitter
s (norepinephrine
, substance P
) are important mediators of degranulation of mast cells or basophils, they are generally not called anaphylatoxins. This term is reserved only for fragments of the complement.
, C4B
, C4B-1, C5
, FBLN1
, FBLN2
C3 (complement)
Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement system and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called C3.-Function:...
, C4a
C4A
Complement C4-A is a protein that in humans is encoded by the C4A gene.-Further reading:...
and C5a
C5a
C5a is a protein fragment released from complement component C5. In humans, the polypeptide contains 74 amino acids. NMR spectroscopy proved that the molecule is composed of four helices and loops connecting the helices. On the N terminus a short 1.5 turn helix is also present. The longest helix...
) that are produced as part of the activation of the complement system
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...
.. Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defense. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments. A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins.: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability. They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals. The proteins are highly hydrophilic, with a mainly alpha-helical structure held together by 3 disulphide bridges.
Function
Anaphylatoxins are able to trigger degranulationDegranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
(release of substances) of endothelial cells, mast cells or phagocytes, which produce a local inflammatory response. If the degranulation is widespread, it can cause a shock-like syndrome similar to that of an allergic reaction.
Anaphylatoxins indirectly mediate:
- smooth muscle cellsSmooth muscleSmooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
contraction, for example bronchospasmBronchospasmBronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...
s - increase in the permeability of blood capillariesCapillaryCapillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
- chemotaxisChemotaxisChemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
— receptorReceptor (biochemistry)In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
-mediated movement of leukocytes in the direction of the increasing concentration of anaphylatoxins
Examples
Important anaphylatoxins:- C5a has the highest specific biological activity and is able to act directly on neutrophils and monocytes to speed up the phagocytosis of pathogens.
- C3a works with C5a to activate mast cells, recruit antibody, complement and phagocytic cells and increase fluid in the tissue, all of which contribute to the initiation of the adaptive immune response.
- C4a is the least active anaphylatoxin.
Terminology
Although some drugs (morphineMorphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, synthetic ACTH) and some neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s (norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, substance P
Substance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
) are important mediators of degranulation of mast cells or basophils, they are generally not called anaphylatoxins. This term is reserved only for fragments of the complement.
Human proteins containing this domain
C3, C4AC4A
Complement C4-A is a protein that in humans is encoded by the C4A gene.-Further reading:...
, C4B
Complement component 4
Complement component 4 is a protein involved in the complement system.It is cleaved into proteins 4a and 4b.* C4a is an anaphylatoxin.* C4b forms part of C3-convertase, in conjunction with 2a:* C4b can bind CR1....
, C4B-1, C5
Complement component 5
Complement component 5 is a protein that in humans is encoded by the C5 gene.Complement component 5 is involved in the complement system. It is cleaved into C5a and C5b:* C5a plays an important role in chemotaxis....
, FBLN1
FBLN1
FBLN1 is the gene encoding fibulin-1, an extracellular matrix and plasma protein.- Function :Fibulin-1 is a secreted glycoprotein that is found in association with extracellular matrix structures including fibronectin-containing fibers, elastin-containing fibers and basement membranes...
, FBLN2
FBLN2
Fibulin-2 is a protein that in humans is encoded by the FBLN2 gene.-Interactions:FBLN2 has been shown to interact with Laminin, alpha 1, Laminin, alpha 5 and Perlecan.-Further reading:...
See also
- AllergyAllergyAn Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
- Anaphylatoxin receptorsAnaphylatoxin receptorsThe anaphylatoxin receptors are a group of G-protein coupled receptors which bind anaphylatoxins. Members of this family include:* C3a receptor * C5a receptor * C5L2...
- AnaphylaxisAnaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
- Complement systemComplement systemThe 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...
- InflammationInflammationInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
- 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...
- Nervous systemNervous systemThe nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...