Defensin, alpha 5

Human Alpha Defensin 5 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 modulate inflammatory processes.

Defensin alpha 5 is a human protein encoded by the DEFA5 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 characterized by a conserved cysteine motif.

The primary synthesis site of defensin alpha 5 is the Paneth cells in the ileum. Furthermore, defensin is found in the granules of neutrophil granulocytes and in the epithelial cells of mucous membrane surfaces of the intestine, respiratory and (lower) urinary tract as well as in the vagina.

Alpha-Defensin 5 has antimicrobial and antiviral properties. It is assumed that all alpha-defensins 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.

To date, the ability of the urinary tract (and other epithelial surfaces) to prevent infections is not fully understood. Human alpha-defensin 5 (HD5) is expressed, among others, in the human kidney and lower urinary tract under physiological conditions. The physiological production of defensin is expected to contribute significantly to the antimicrobial capacity of the uroepithelium (Spencer JD et al. 2012). In pyelonephritis there is a significant increase in the expression of alpha-defensin 5 (and other defensins?).

The antiviral potency (proven in adenoviruses and human papillomaviruses) of defensin alpha 5 represents a stoichiometric (from gr. stoicheion "basic substance" and metron "measure") function which is determined by the specific tertiary and quaternary structure (several protein molecules assemble to form a functional complex) and by the electrical charge of the antimicrobial peptide. Together with a hydrophobic property of the defensin complex, the viruses are neutralized by the defensin (Tenge VR et al. 2014).

In infantile Crohn's patients, an enefall increase in defensin-alpha-5 expressions in the inflammatory mucosa was detected (Zilbauer M et al. 2011).

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