Alpha-defensins are a family of small cationic antimicrobial peptides (29-35 amino acids, MW ~3.5-4.5 kDa) with three characteristic intramolecular disulfide bonds. Human neutrophil peptides (HNP-1 through HNP-4) are stored in azurophilic granules and released during neutrophil degranulation, while human defensins HD-5 and HD-6 are produced by Paneth cells in the small intestinal crypts. They are major effectors of innate immunity and endogenous reference molecules.
Category: Antimicrobial / Immune. Evidence rating: D (animal/preclinical only).
Clinical status: Endogenous peptides. No therapeutic product in clinical development. Studied as biomarkers (e.g., synovial fluid alpha-defensin test for periprosthetic joint infection).
Alpha-defensins are cationic peptides with a triple-stranded beta-sheet structure stabilized by three disulfide bonds (Cys1-Cys6, Cys2-Cys4, Cys3-Cys5 connectivity). They kill bacteria through electrostatic interaction with anionic microbial membranes, forming pores or disrupting membrane…
Safety considerations: Endogenous peptides naturally present in neutrophils and Paneth cells; Elevated circulating HNP levels are associated with cardiovascular risk and systemic inflammation; No exogenous therapeutic products exist for safety evaluation.
Reviewed by the PeptideAtlas Editorial Team. Last reviewed: 2026-08-12.
Related peptides: LL-37, Beta-Defensins, Lactoferricin.
Compare: Alpha-Defensins vs LL-37, Alpha-Defensins vs Beta-Defensins, Alpha-Defensins vs Lactoferricin.
The Synovasure lateral flow test measures alpha-defensin (primarily HNP-1 through HNP-3) in synovial fluid as a diagnostic biomarker for periprosthetic joint infection. It has demonstrated >97% sensitivity and specificity and is commercially available as a point-of-care test.
Alpha-defensins have a different disulfide bond connectivity pattern (Cys1-6, Cys2-4, Cys3-5 vs Cys1-5, Cys2-4, Cys3-6 in beta-defensins), are shorter (29-35 vs 36-45 amino acids), and are primarily produced by neutrophils and Paneth cells rather than epithelial cells.
Yes. Paneth cell defensins HD-5 and HD-6 are critical for maintaining intestinal microbial homeostasis. Reduced HD-5/HD-6 expression has been linked to ileal Crohn disease, and HD-6 uniquely forms nanonets that physically trap bacteria in the gut lumen.