Alpha defensins are a family of mammalian defensin peptides. Defensins are 2-6 kDa, cationic, microbicidal peptides active against many Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses, containing three pairs of intramolecular disulfide bonds. On the basis of their size and pattern of disulfide bonding, mammalian defensins are classified into alpha, beta and theta categories. Alpha-defensins, which have been identified in humans, monkeys and several rodent species, are particularly abundant in neutrophils, certain macrophage populations and Paneth cells of the small intestine. Defensins are produced constitutively and/or in response to microbial products or proinflammatory cytokines. The mechanism(s) by which microorganisms are killed and/or inactivated by defensins is generally believed as a consequence of disruption of the microbial membrane. The polar topology of defensins, with spatially separated charged and hydrophobic regions, allows them to insert themselves into the phospholipid membranes so that their hydrophobic regions are buried within the lipid membrane interior and their charged (mostly cationic) regions interact with anionic phospholipid head groups and water. Subsequently, some defensins can aggregate to form "channel-like" pores; others might bind to and cover the microbial membrane in a "carpet-like" manner. The net outcome is the disruption of membrane integrity and function, which ultimately leads to the lysis of microorganisms. Initially human alpha defensin peptides were isolated from the neutrophils and are thus called human neutrophil peptides (HNPs). Human neutrophil peptides are also known as α-defensins.α-defensin-1 also known as HNP1 human neutrophil peptide 1, having the sequence ACYCRIPACIAGERRYGTCIYQGRLWAFCC. Human neutrophil peptides are found in human atherosclerotic arteries, inhibit LDL metabolism and fibrinolysis.
HNP1 has been reported to increase the production of tumor necrosis factor (TNF) and IL-1, while decreasing the production of IL-10 by monocytes. Increased levels of proinflammatory factors (e.g., IL-1, TNF, histamine and prostaglandin D2) and suppressed levels of IL-10 at the site of microbial infection are likely to amplify local inflammatory responses. The capacity of defensins to enhance phagocytosis, promote neutrophil recruitment, enhance the production of proinflammatory cytokines, suppress anti-inflammatory mediators and regulate complement activation argues that defensins upregulate innate host inflammatory defenses against microbial invasion.