α-Defensins in human innate immunity

Defensins are small, multifunctional cationic peptides. They typically contain six conserved cysteines whose three intramolecular disulfides stabilize a largely beta-sheet structure. This review of human alpha-defensins begins by describing their evolution, including their likely relationship to the Big Defensins of invertebrates, and their kinship to the beta-defensin peptides of many if not all vertebrates, and the beta-defensins found in certain non-human primates. We provide a short history of the search for leukocyte-derived microbicidal molecules, emphasizing the roles played by luck (good), preconceived notions (mostly bad), and proper timing (essential). The antimicrobial, antiviral, antitoxic, and binding properties of human alpha-defensins are summarized. The structural features of alpha-defensins are described extensively and their functional contributions are assessed. The properties of HD6, an enigmatic Paneth cell alpha-defensin, are contrasted with those of the four myeloid alpha-defensins (HNP14) and of HD5, the other alpha-defensin of human Paneth cells. The review ends with a decalogue that may assist researchers or students interested in alpha-defensins and related aspects of neutrophil function.