Defensin

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Defensins are small (15-20 residue) cysteine-rich cationic proteins found in both vertebrates and invertebrates. They are active against bacteria, fungi and enveloped viruses. They consist of 15-20 amino acids including six to eight 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 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 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

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

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]

References

  1. MeSH retrocyclin
  2. 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. PMID 15772169. 
  3. Philpott M (2003). "Defensins and acne.". Mol Immunol. 40 (7): 457–62. PMID 14568392. 
  4. Genomics & Genetics Weekly, "Researchers discover a possible cause of chronic inflammations of Crohn Disease." August 11, 2006, page 72
  5. Wehkamp J; et al. (2005). "Reduced Paneth cell alpha-defensins in ileal Crohn's disease". Proc Natl Acad Sci U S A. 102 (50): 18129–34. PMID 16330776. 

External links



de:Defensin


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