Defensin, alpha 2

Human Alpha Defensin 2 belongs to the large group of antimicrobial peptides (AMP), a heterogeneous group of naturally occurring small (< 100 amino acids), cationic amphiphilic peptides with broad microbicidal activity, known as "endogenous antibiotics". Antimicrobial peptides are synthesized by plants, bacteria, insects, invertebrates and vertebrates.

Human antimicrobial peptides play a major role in the innate, non-specific immune defence (see below immunity, innate) within the framework of an epithelial barrier function in the respiratory, urogenital and gastrointestinal tracts as well as in the skin in defending against infectious pathogens. In addition to the cellular epithelial barrier they represent a kind of chemical barrier. Besides their direct antimicrobial functions they act as initiators of inflammatory processes.

The human defensin alpha 2, also known as human neutrophil peptide 2, HNP-2, is a human protein encoded by the DEFA2 gene, which is located on chromosome 8 p23.1 in a gene cluster together with other AMP genes. The members of the defensin family are very similar in their protein sequence and are distinguished by a conserved cysteine motif. The human defensin alpha 2 is synthesized from a precursor molecule in bone marrow cells.

The defensins alpha 1 and alpha 2 have antibacterial, fungicidal and antiviral activities. Their antimicrobial activity is directed against Gram-negative and Gram-positive bacteria. Furthermore, antiviral effectiveness can also be demonstrated (Wilson SS et al. 2013).

The primary structure of alpha-defensin-1 (HNP-1), alpha-defensin-2 (HNP-2) and alpha-defensin-3 (HNP-3 ) differ only slightly.

It is assumed that defensins combat pathogens by forming pores in the cell wall, which leads to a loss of membrane stability and ultimately to the death of the pathogen.

Apparently, the level of serum cholesterol influences the expression of the genes of alpha-defensins 1, 2 and 3. After treatment with statins this finding normalizes (Li YX et al. 2014).

Also in diabetic patients significantly elevated levels of human defensins alpha1,2,3 and human defensin beta-1 are detected. An additionally increased overexpression is detected in diabetic patients with nephropathy and/or neuropathy (Németh BC et al. 2014).

In various In various studies it has been shown that human alpha-defensin-2 is an important component in squamous cell carcinoma of the tongue.

Alpha-defensin-2 (HNP2) seems to be as efficient in neutralizing anthrax toxin as alpha-defensin-1, and it is also able to block papillomavirus infections.

The biological role seems to go far beyond what is known so far. The cooperative functions of alpha-defensin-1,2,-3 (HNP-1, HNP-2 and HNP-3) need to be clarified.

Furthermore, human neutrophil peptides are detected in atherosclerotic arteries. They inhibit LDL metabolism and fibrinolysis.

1. Buck CB et al (2006) Inhibition of Papillomavirus infection. Proc Natl Acad Sci 103: 1516)
2. Kim C. et al (2005) Neutralization of Anthrax Lethal Toxin Proc Natl Acad Sci 102: 4830
3. Küçükkolbaşi H et al (2011) Determination of defensin HNP-1 in human saliva of patients with oral mucosal diseases. J Immunoassay Immunochem 32:284-295.
4. Li YX et al (2014) Upregulated expression of human alpha-defensins 1, 2 and 3 in hypercholesteremia and its relationship with serum lipid levels. Hum Immunol 75:1104-1109.
5. Németh BC et al (2014) Relevance of α-defensins (HNP1-3) and defensin β-1 in diabetes. World J Gastroenterol 20:9128-9237.
6. Salzman NH et al (2010) Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 11:76-83.
7. Wilson SS et al (2013) Antiviral mechanisms of human defensins. J Mol Biol 425:4965-4980.
8. Zhao L et al (2014) Defensins in innate immunity. Curr Opin Hematol 21:37-42.