Utente:PinoEire/Defensine
Le Defensine sono piccole proteine cationiche ricche di cisteina che si trovano sia nei vertebrati che negli invertebrati. Sono attive contro batteri, funghi e virus pericapside. Le defensine sono composte di 15-20 amminoacidi, compresi da sei a otto residui di cisteina. Le cellule del sistema immunitario contengono questi peptidi per aiutare nell'eliminazione dei batteri fagocitati, per esempio nei granulociti neutrofili e quasi in tutte le cellule epiteliali. La maggior parte delle defensine funziona penetrando la membrana cellulare microbica attraverso attrazione elettrica, ed una volta all'interno forma un poro nella membrana permettendo così il deflusso.
Tipi[modifica | modifica wikitesto]
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, DEFA5, 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). |
| 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 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 | DEFT1P | Are rare, and thus far have been found only in the leukocytes of the rhesus macaque. |
Function[modifica | modifica wikitesto]
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[1] 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.[2]
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[modifica | modifica wikitesto]
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]
References[modifica | modifica wikitesto]
- ^ (EN) retrocyclin, in Medical Subject Headings (MeSH), National Library of Medicine, 2009.
- ^ Kim C, Gajendran N, Mittrücker H, Weiwad M, Song Y, Hurwitz R, Wilmanns M, Fischer G, Kaufmann S, Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences, in Proc Natl Acad Sci U S a, vol. 102, n. 13, 2005, pp. 4830–5, DOI:10.1073/pnas.0500508102.
- ^ Philpott M, Defensins and acne, in Mol Immunol, vol. 40, n. 7, 2003, pp. 457–62, DOI:10.1016/S0161-5890(03)00154-8.
- ^ Genomics & Genetics Weekly, "Researchers discover a possible cause of chronic inflammations of Crohn Disease." August 11, 2006, page 72
- ^ Wehkamp J et al, Reduced Paneth cell alpha-defensins in ileal Crohn's disease, in Proc Natl Acad Sci U S a, vol. 102, n. 50, 2005, pp. 18129–34, DOI:10.1073/pnas.0505256102.
- ^ Craddock RM, Huang JT, Jackson E, et al, Increased alpha defensins as a blood marker for schizophrenia susceptibility, in Mol. Cell Proteomics, vol. 7, March 2008, p. 1204, DOI:10.1074/mcp.M700459-MCP200.
External links[modifica | modifica wikitesto]
- Defensins Database, Singapore
- Innate ( Nonspecific ) Immunity at Western Kentucky University
- Template:UMichOPM - Vertebrate defensins and related sea anemone sodium channel toxins
- Template:UMichOPM - Defensins from insects and plants and scorpion toxins
- (EN) Defensins, in Medical Subject Headings (MeSH), National Library of Medicine, 2009.
[[Category:Hematology]] [[Category:Peripheral membrane proteins]]