α‐Defensins in human innate immunity

Summary:  Defensins are small, multifunctional cationic peptides. They typically contain six conserved cysteines whose three intramolecular disulfides stabilize a largely β‐sheet structure. This review of human α‐defensins begins by describing their evolution, including their likely relationship to the Big Defensins of invertebrates, and their kinship to the β‐defensin peptides of many if not all vertebrates, and the θ‐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 α‐defensins are summarized. The structural features of α‐defensins are described extensively and their functional contributions are assessed. The properties of HD6, an enigmatic Paneth cell α‐defensin, are contrasted with those of the four myeloid α‐defensins (HNP1–4) and of HD5, the other α‐defensin of human Paneth cells. The review ends with a decalogue that may assist researchers or students interested in α‐defensins and related aspects of neutrophil function.