Anaphylatoxins, or complement peptides, are fragments (
C3a,
C4a and
C5a) that are produced as part of the activation of the
complement system
The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inf ...
.
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, vasodilation, 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 disulfide bridges.
Function
Anaphylatoxins are able to trigger
degranulation (release of substances) of
endothelial cells,
mast cells
A mast cell (also known as a mastocyte or a labrocyte) 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 ...
or
phagocytes
Phagocytes are cell (biology), cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or Apoptosis, dying cells. Their name comes from the Greek language, Greek ', "to eat" or "devour", and "-cyte", the suffix in ...
, 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
Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...
.
Anaphylatoxins indirectly mediate:
*
smooth muscle cells contraction, for example
bronchospasms
* increase in the permeability of
blood capillaries
* C5a indirectly mediates
chemotaxis
Chemotaxis (from ''chemical substance, chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell organism, single-cell or multicellular organisms direct thei ...
—
receptor
Receptor may refer to:
* Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
-mediated movement of
leukocyte
White blood cells (scientific name leukocytes), 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 entities. White blood cells are genera ...
s 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 (
morphine
Morphine, formerly also called morphia, is an opiate that is found naturally in opium, a dark brown resin produced by drying the latex of opium poppies (''Papaver somniferum''). It is mainly used as an analgesic (pain medication). There are ...
,
codeine, synthetic
ACTH) and some
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.
Neurotra ...
s (
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
,
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 system.
Human proteins containing this domain
C3,
C4A,
C4B,
C4B-1,
C5,
FBLN1,
FBLN2
See also
*
Allergy
Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...
*
Anaphylatoxin receptors
*
Anaphylaxis
Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...
*
Complement system
The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inf ...
*
Inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
*
Immune system
The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
*
Nervous system
In biology, the nervous system is the complex system, highly complex part of an animal that coordinates its behavior, actions and sense, sensory information by transmitting action potential, signals to and from different parts of its body. Th ...
References
Further reading
*
*
External links
*
{{InterPro content, IPR000020
Complement system
Protein families