Defensin, alpha 3

Human Alpha Defensin 3 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 3, also known as human neutrophilic peptide 3, HNP-3, is a human protein encoded by the DEFA3 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. Thus, the primary structure of defensin, alpha 1 (HNP-1), defensin, alpha 2 (HNP-2) and alpha-defensin-3 (HNP-3 ) differs only slightly.

The alpha-defensins 1-3 belong to the immunologically active proteins that are formed and secreted by dendritic cells (MDDC=Monocytes derived digital cells) and neutrophilic granulocytes. They play an important role in natural and adaptive immunity (Escribese MM et al. 2011). For example, the MDDC-initiated production of defensins 1-3 is significantly increased in HIV-infected persons. (Rodríguez-García M et al. 2010) The possible cooperative, also similar (or even additive) functions of alpha-defensin-1,2,-3 (HNP-1, HNP-2 and HNP-3) need to be clarified.

All alpha-defensins have antimicrobial properties in common. Defensins are thought to fight pathogens by forming pores in the cell wall, which leads to a loss of membrane stability and ultimately to the death of the pathogen (see below antimicrobial peptides).

Further biological functions of defensin alpha 3:

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). Associated with the increased gene expression was an increased rate of coronary heart disease.

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

In patients with chronic myeloid leukemia (CML) who responded positively to imatinib, a sustained reduction of defensins alpha 1-3 and defensin alpha 4 was demonstrated. In contrast, imatinib-resistant recurrences of the disease showed a dramatic increase of these peptides, although this only affected defensin alpha 4 to a lesser extent (Etienne G et al.2011).

1. Escribese MM et al (2011) Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen. Reprod Biol Endocrinol 9:118.
2. Etienne G et al (2011) α-defensin 1-3 and α-defensin 4 as predictive markers of imatinib resistance and relapse in CML patients. Dis markers 30:221-227.
3. 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.
4. Németh BC et al (2014) Relevance of α-defensins (HNP1-3) and defensin β-1 in diabetes. World J Gastroenterol 20:9128-9237.
5. Rodríguez-García M et al. (2010) Increased α-Defensins 1-3 Production by Dendritic Cells in HIV-Infected Individuals Is Associated with Slower Disease Progression. PLoS One 5: e9436.
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.