Antimicrobial and antiviral effects of human defensins: pathogenetic value and prospective application to medicinal therapy

Abstract

Defensins, the cationic antimicrobial peptides (AMPs) of phagocytes and epithelial cells, are the key effector molecules of the innate immune system providing the anti-infective host defense. Besides the antimicrobial action, AMPs exert a broad spectrum of varied effects towards host cells giving a ground for considering these peptides as possible biomodulatory molecules. The review outlines different types of the biological activity of structurally diverse AMPs. AMPs posses the potent antimicrobial, antiviruses and lipopolysaccharide-binding activity; some of them are cytotoxic for tumor and normal human cells in vitro, while others demonstrate the wound healing action. AMPs of the defensin family display the corticostatic activity: they inhibit stimulated by adrenocorticotropic hormone (ACTH) steroidogenesis in adrenal cells in vitro. We also showed that defensins and protegrin 3 abolish ACTH- or stress-induced increase of the corticosterone level in blood of experimental animals. Taken together, the described in the literature and our own data contribute to the idea that AMPs are the multifunctional molecules participating in the interaction between the innate and adaptive immune systems as well as between immune and neuroendocrine systems. It considers structure and mechanism of defensins interaction with lipid membrane and intracellular targets of pathogens. Special attention is paid to modern state and perspectives of defensins practical application and also to approaches that increase efficacy by chemical modification of their structure.