Defensin, beta 3

Human Beta 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 also act as moderators of inflammatory processes.

All beta-defensins have antimicrobial properties in common. They contain a stabilizing cysteine motif. Defensins are thought to fight pathogens by forming pores in the cell wall (Sudheendra US et al. 2015), which leads to a loss of membrane stability and ultimately to the death of the pathogen (see below antimicrobial peptides). The members of the beta-defensin family have similar protein sequences.

Beta-Defensin 3 (BD-3) also known as "skin-antimicrobial peptide 2", SAP2, is a cysteine-rich, human, cationic, antimicrobial peptide with a dimeric structure. Structurally, however, beta-defensin 3 differs significantly from beta-defensins 2 and 1.

The peptide consists of 45 amino acids with 3 disulfide bridges that give the molecule a special stability. Beta-Defensin 3 is encoded by the DEFB3 gene (also called DEFB103) located on the short arm of the 8th chromosome (8p23.1).

Beta-defensin 3 (hBD3) is an almost ubiquitously occurring "antibiotic" peptide that is regulated by inflammatory processes. Together with human beta defensin 3 (hBD3), human beta defensin 2 is one of the most important members of the beta-defensin family.

Beta-Defensin 3 was initially obtained from psoriatic dandruff. It is now known that HBD-3 is physiologically widely expressed in the epithelia of the following organs: skin, trachea, pharynx, larynx, tongue and tonsils. To a lesser extent also in the salivary glands, uterus, kidneys, bone marrow, thymus, colon. Beta-Defensin 3 is characterized by relevant antibacterial activities against Gram-negative and Gram-positive bacteria. This is significantly more pronounced than that of HBD1 and hBD2.

Furthermore, antimicrobial activities relevant for defensin beta 3 could be shown against methicillin-resistant Staphylococcus aureus (MRSA) - and vancomycin-resistant Enterococcus faecium strains. Also in the treatment of MRSA biofilm formations. This could lead to new therapeutic approaches (Sutton JM et al. 2014).

Beta Defensin 3 and Beta Defensin 2 influence the viability of Helicobacter pylori. In vitro, it could be shown that the expression of human beta defensin 2 was increased up to 40 times the initial value, depending on Helicobacter pylori infection. In vivo, the degree of upregulation correlated with the extent of antrum gastritis. In contrast, the levels of human defensin beta 3 decreased while mRNA remained unchanged. With eradication of H. pylori the values of human defensin beta 2 normalized (Bauer B et al. 2013). Furthermore, it has a chemoattractive effect (Dhople V et al. 2006).

HBD 3 inhibits the lipopolysaccharide-induced production of oxygen radicals as well as inflammatory cytokines such as interleukin-6 and the tumor necrosis factor alpha. In an inflammation model with lung parenchyma, hBD 3 reduces the inflammatory cellular infiltrate. It is therefore classified as an anti-inflammatory regulatory protein.

HBD3 is involved in the maturation process of Th1 lymphocytes and human Langerhans-cell-like dendritic cells (LC-DCs). This process is associated with an increased expression of the chemokine receptor CCR7, which mediates chemotactic responses of the chemokines CCL19 and CCL21. These interactions reflect essential functions of the natural and adaptive immune system (Ferris LK et al 2013).

1. Bauer B et al (2013) Differential expression of human beta defensin 2 and 3 in gastric mucosa ofHelicobacter pylori-infected individuals. Helicobacter 18:6-12.
2. Dhople V et al (2006) The human beta-defensin-3, an antibacterial peptide with multiple biological functions. Biochim Biophys Acta 1758:1499-512.
3. Donlan RM et al (2002) Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 15:167.
4. Ferris LK et al (2013) Human beta-defensin 3 induces maturation of human langerhans cell-like dendritic cells: an antimicrobial peptide that functions as an endogenous adjuvant. J Invest Dermatol 133:460-468.
5. Sudheendra US et al (2015) Membrane disruptive antimicrobial activities of human β-defensin-3 analogues. Eur J Med Chem 91:91-99.
6. Sutton JM et al (2014) Human beta-defensin 3: a novel inhibitor of Staphylococcus-Produced biofilm production. Commentary on Human β-defensin 3 inhibits antibiotic-resistant Staphylococcus biofilm formation. J Surg Res 186: 99-100.