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Defensin
From Wikipedia, the free encyclopedia
Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates. They are active against bacteria, fungi and many enveloped and nonenveloped viruses. They consist of 18-45 amino acids including six (in vertebrates) to 8 conserved cysteine residues. Cells of the immune system contain these peptides to assist in killing phagocytized bacteria, for example in neutrophil granulocytes and almost all epithelial cells. Most defensins function by binding to microbial cell membrane, and once embedded, forming pore-like membrane defects that allow efflux of essential ions and nutrients.
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[edit] Varieties
The underlying genes responsible for defensin production are highly 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.
| Type | Genes | Description |
| α-defensins | DEFA1, DEFA1A3, DEFA3, DEFA4 | Are expressed primarily in neutrophils as well as in NK cells and certain T-lymphocyte subsets. DEFA5 and DEFA6 are expressed in Paneth cells of the small intestine, where they may regulate and maintain microbial balance in the intestinal lumen. |
| β-defensins | DEFB1, DEFB4, DEFB103A/DEFB103B to DEFB107A/DEFB107B, DEFB110 to 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 has been suggested (but also challenged) 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. |
| θ-defensins | DEFT1P | Are rare, and thus far have been found only in the leukocytes of the rhesus macaque and the olive baboon, Papio anubis. |
[edit] 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 humanized theta-defensin[1] created artificially by `fixing' a human pseudogene - is effective against HIV and other viruses, including herpes simplex and influenza A. They act primarily by preventing the these viruses from entering their target cells.
Also interesting is the effect of alpha-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.[2]
[edit] Pathology
An imbalance of defensins in the skin may contribute to acne.[3]
A reduction of ileal defensins may predispose to Crohn's disease.[4][5]
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.[6]
[edit] References
- ^ MeSH retrocyclin
- ^ Kim C, Gajendran N, Mittrücker H, Weiwad M, Song Y, Hurwitz R, Wilmanns M, Fischer G, Kaufmann S (2005). "Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences". Proc Natl Acad Sci U S a 102 (13): 4830–5. doi:. PMID 15772169.
- ^ Philpott M (2003). "Defensins and acne". Mol Immunol 40 (7): 457–62. doi:. PMID 14568392.
- ^ Genomics & Genetics Weekly, "Researchers discover a possible cause of chronic inflammations of Crohn Disease." August 11, 2006, page 72
- ^ Wehkamp J et al (2005). "Reduced Paneth cell alpha-defensins in ileal Crohn's disease" (abstract). Proc Natl Acad Sci U S a 102 (50): 18129–34. doi:. PMID 16330776, http://www.pnas.org/cgi/content/abstract/102/50/18129.
- ^ Craddock RM, Huang JT, Jackson E, et al (March 2008). "Increased alpha defensins as a blood marker for schizophrenia susceptibility". Mol. Cell Proteomics 7: 1204. doi:. PMID 18349140, http://www.mcponline.org/cgi/pmidlookup?view=long&pmid=18349140.
[edit] External links
- Defensins Database, Singapore
- Innate ( Nonspecific ) Immunity at Western Kentucky University
- UMich Orientation of Proteins in Membranes families/superfamily-56 - Vertebrate defensins and related sea anemone sodium channel toxins
- UMich Orientation of Proteins in Membranes families/superfamily-61 - Defensins from insects and plants and scorpion toxins
- MeSH Defensins
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