Defensin, alpha 4

Human Alpha Defensin 4 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 4, also known as human neutrophilic peptide 4, HNP-4, is a human protein encoded by the DEFA4 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 gene DEFA4 differs from other defensin genes by a particular 83 base segment which is probably the result of a duplication within the coding region. The protein encoded by this gene, defensin alpha 4, inhibits the corticotropin-stimulated production of corticoids.

Alpha-Defensin 4 is mainly formed in neutrophil granulocytes and is also detectable there. It has antimicrobial and antiviral (in vitro, human -neutrophile- alpha-defensin 4 inhibits the activity of HIV-1) properties. It is assumed that all (neutrophil) alpha-defensins fight pathogens by pore formation 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 4:

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

Human alpha defensin alpha 4 was first isolated as "corticostatin" in neutrophil granulocytes. The defensin is an antagonist of ACTH (Singh et al.1988) and inhibits ACTH-dependent corticosteroid production.

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