Defensin, alpha 1

Human defensin alpha 1 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 via pathogen recognition receptors.

Human defensin alpha 1, also known as human neutrophilic peptide 1, HNP-1, is a human protein encoded by the DEFA1 gene 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 precursors of human defensin alpha 1 are mainly processed in promyelocytes. There they are attached to the proteoglycan serglycine in the azurophilic granules. In later stages of granulocyte maturation they are enriched there.

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

Defensins are thought to combat microbes by forming pores in the cell wall of the pathogen, which leads to a loss of membrane stability and ultimately to their death.

An analogous mechanism could be demonstrated for the human defensin alpha-1 in the defence of Trypanosoma cruzi. The toxic destructive effects are also caused in these parasites by pore formation in the cell membrane and by fragmentation of their mitochondrial DNA.

Further biological functions:

Human defensin alpha-1 can be detected in relevant concentrations in the saliva of healthy volunteers (concentrations: 0.10 - 0.90 μg/10 μL). The defensin alpha-1 co-centrations of patients with oral mucosal diseases such as lichen planus mucosae, Behçet's disease or with recurrent aphthae formation were significantly increased compared to non-affected persons (Küçükkolbaşi H et al. 2011).

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 normalises (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).

1. 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.
2. 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.
3. Madison MN et al (2007) Human defensin alpha-1 causes Trypanosoma cruzi membrane pore formation and induces DNA fragmentation, which leads to trypanosome destruction. Infect Immune 75:4780-4791.
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. Salzman NH et al (2010) Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 11:76-83.
6. Wilson SS et al (2013) Antiviral mechanisms of human defensins. J Mol Biol 425:4965-4980.
7. Zhao L et al (2014) Defensins in innate immunity. Curr Opin Hematol 21:37-42.