Mammalian antimicrobial peptides play an important part of the innate immune system. These peptides are classified based on secondary structural features, such as cathelicidins (with a linear α-helical structure), defensins (with a β-strand structure), and bactenecins (with a loop structure). Currently, there are two main genetic categories for antimicrobial peptides in mammals the cathelicidins and defensins. Cathelicidins are characterized by an NH2-terminal signal peptide (a highly conserved cathelin domain) and a variable COOH-terminal antimicrobial domain.
The defensins are small cysteine-rich cationic proteins consisting of 18-45 amino acids folded into β-pleated sheet structures stabilized by three intramolecular disulphide bonds. The mammalian are classified in three different classes the α-, β, θ defensins which differ in their distribution of disulphide bonds. Currently, six α-defensins and four β-defensins (hBD 1–4) have been well characterized.
Leukocytes and epithelial cells are the main sources of mammalian defensins. So far, six human α-defensins have been identified. HNP1, HNP2 and HNP3, which differ only in the first amino acid, account for 5–7% of total neutrophil proteins. By contrast, HNP4, which has an amino-acid sequence distinct from the HNP1, HNP2 and HNP3 sequences, comprises less than 2% of total defensins in neutrophils.
Although leukocyte defensins are conserved evolutionally and have been isolated from many species, including humans, rabbits and rats, mice lack α-defensin expression by neutrophils. Instead, mice express many enteric α-defensin-like peptides known as cryptidins.
Similarly, in humans HD5 and HD6 are produced mainly by intestinal Paneth cells in the small intestine but are also found in other tissues, such as the salivary glands and the female genital tract. In regard to β-defensins, the first β-defensin was identified in bovine tongue, whereas the first isolated human β-defensin-1 (hBD-1) was discovered from hemofiltrates. Today approximately 28 human β-defensins have been identified by gene-based searches; six human β-defensins (hBD-1, -2, -3, -4, -5 and -6) are expressed mainly by epithelial cells.
Whereas hBD-1 is constitutively expressed by epithelial cells, expression of hBD-2 can be induced by viruses, bacteria, microbial products and pro-inflammatory cytokines, such as tumor-necrosis factor (TNF) and interleukins.The θ-defensins have been found only in leukocytes from rhesus macaques (RTD1, RTD2 and RTD3). Although RNA transcripts homologous to the rhesus θ-defensin gene are found in human bone marrow, these transcripts contains premature stop codon in the upstream signal sequence, which abolishes subsequent translation and are thought to belong to the pseudogenes in humans.
Defensins
