Defensin
1772092
224599639
2008-07-09T16:26:08Z
199.125.16.11
/* Pathology */
'''Defensins''' are small (15-20 [[residue]]) [[cysteine]]-rich [[cationic]] [[proteins]] found in both [[vertebrate]]s and [[invertebrate]]s. They are active against [[bacteria]], [[fungus|fungi]] and enveloped [[viruses]]. They consist of 15-20 [[amino acid]]s including six to eight conserved [[cysteine]] residues. Cells of the [[immune system]] contain these peptides to assist in killing [[Phagocyte|phagocytized]] bacteria, for example in [[neutrophil granulocyte]]s and almost all [[epithelial cells]]. Most defensins function by penetrating the [[microbial]]'s [[cell membrane]] by way of electrical attraction, and once embedded, forming a pore in the membrane which allows [[efflux]].
==Varieties==
The underlying genes responsible for defensin production are highly [[Polymorphism (biology)|polymorphic]]. Some aspects are conserved, however; the hallmarks of a β-defensin are its small size, high density of cationic charge and six-cysteine-residue motif. Generally they are encoded by two-[[exon]] genes, where the first exon encodes for a hydrophobic leader sequence and the second for a peptide containing the cysteine motif.
There are three main (known) forms of mammalian defensins; α-defensins, β-defensins, and θ-defensins.
{| class="wikitable"
| '''Type''' || '''Genes''' || '''Description'''
|-
| [[Alpha defensin|α-defensins]] || {{Gene|DEFA1}}, {{Gene|DEFA1A3}}, {{Gene|DEFA3}}, {{Gene|DEFA4}}, {{Gene|DEFA5}}, {{Gene|DEFA6}}|| Are expressed primarily in [[neutrophils]] as well as [[macrophages]] and the [[Paneth cells]] of the intestines (where they help maintain the correct microbial balance).
|-
| [[Beta defensin|β-defensins]] || {{Gene|DEFB1}}, [[DEFB4]], {{Gene|DEFB103A}}/{{Gene|DEFB103B}} to {{Gene|DEFB107A}}/{{Gene|DEFB107B}}, {{Gene|DEFB110}} to {{Gene|DEFB133}} || Are the most widely distributed, being secreted by [[leukocytes]] and [[epithelial]] cells of many kinds. For example, they can be found on the tongue, skin, cornea, salivary glands, kidneys, esophagus, and respiratory tract. It is theorised that some of the pathology of [[cystic fibrosis]] arises from the inhibition of β-defensin activity on the epithelial surfaces of the lungs and trachea due to higher salt content. These small cells might someday be incorporated onto bioengineered skin grafts for burn victims to boost their ability to repel infections at a critical phase, according to a University of Cincinnati study at Shriner's Hospital for Children.
|-
| θ-defensins || {{Gene|DEFT1P}} || Are rare, and thus far have been found only in the leukocytes of the [[rhesus macaque]].
|}
==Function==
In immature [[marsupials]], because their [[immune system]] is underdeveloped at the time of birth, defensins play a major role in defense against [[pathogens]]. They are produced in the milk of the mother as well as by the young marsupial in question. It is also interesting to note that '''retrocyclin''' - a theta-defensin<ref>{{MeshName|retrocyclin}}</ref> created artificially by `fixing' a human [[pseudogene]] - is effective against HIV, though the mechanism by which it does this is unknown.
Also interesting is the effect of defensins on the [[exotoxin]] produced by anthrax ([[bacillus anthracis]]). Chun Kim et. al showed how anthrax, which produces a [[metalloprotease]] Lethal Factor (LF) protein to target [[MAPKK]], is vulnerable to human neutrophil protein-1 (HNP-1). This group showed HNP-1 to behave as a reversible noncompetitive inhibitor of LF.<ref>{{cite journal | author = Kim C, Gajendran N, Mittrücker H, Weiwad M, Song Y, Hurwitz R, Wilmanns M, Fischer G, Kaufmann S | title = Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences | journal = Proc Natl Acad Sci U S a | volume = 102 | issue = 13 | pages = 4830–5 | year = 2005 | pmid = 15772169 | doi = 10.1073/pnas.0500508102}}</ref>
Defensins are contained in the [[sebum]] secreted by the [[Sebaceous gland]] which melts at 30 degrees celsius. Most people in industrialised countries remove the [[sebum]] and therefore the defensins every day in the shower.
==Pathology==
An imbalance of defensins in the skin may contribute to acne.<ref>{{cite journal | author = Philpott M | title = Defensins and acne | journal = Mol Immunol | volume = 40 | issue = 7 | pages = 457–62 | year = 2003 | pmid = 14568392 | doi = 10.1016/S0161-5890(03)00154-8}}</ref>
A reduction of [[ileum|ileal]] defensins may predispose to [[Crohn's disease]].<ref name=> Genomics & Genetics Weekly, "Researchers discover a possible cause of chronic inflammations of Crohn Disease." August 11, 2006, page 72 </ref><ref>{{cite journal |author=Wehkamp J et al |title=Reduced Paneth cell alpha-defensins in ileal Crohn's disease |journal=Proc Natl Acad Sci U S a |volume=102 |issue=50 |pages=18129–34 |year=2005 |pmid=16330776 |url=http://www.pnas.org/cgi/content/abstract/102/50/18129 |doi=10.1073/pnas.0505256102 |format=abstract}}</ref>
In one small study, a significant increase in [[alpha defensin]] levels was detected in [[T cell]] lysates of [[schizophrenia]] patients; in discordant twin pairs, unaffected twins also had an increase, although not as high as that of their ill siblings. The authors suggested that alpha-defensin levels might prove a useful marker for schizophrenia risk.<!--
--><ref name="pmid18349140">{{cite journal |author=Craddock RM, Huang JT, Jackson E, ''et al'' |title=Increased alpha defensins as a blood marker for schizophrenia susceptibility |journal=[[Mol. Cell Proteomics]] |volume= 7|issue= |pages= 1204|year=2008 |month=March |pmid=18349140 |doi=10.1074/mcp.M700459-MCP200 |url=http://www.mcponline.org/cgi/pmidlookup?view=long&pmid=18349140}}</ref>
==References==
{{Reflist|2}}
==External links==
* [http://defensins.bii.a-star.edu.sg/ Defensins Database, Singapore]
* [http://bioweb.wku.edu/courses/biol328/Innate.htm Innate ( Nonspecific ) Immunity] at [[Western Kentucky University]]
* {{UMichOPM|families|superfamily|56}} - Vertebrate defensins and related sea anemone sodium channel toxins
* {{UMichOPM|families|superfamily|61}} - Defensins from insects and plants and scorpion toxins
* {{MeshName|Defensins}}
[[Category:Hematology]]
[[Category:Peripheral membrane proteins]]
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[[pl:Defenzyna]]
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[[fi:Defensiini]]
[[zh:防御素]]