Research Only Immune & Anti-Inflammatory

HNP-1

also known as: human neutrophil peptide 1, human α-defensin 1, DEFA1, defensin α1, myeloid-related sequence peptide 30a

The prototype human α-defensin — isolated from neutrophil granules by Ganz, Selsted and Lehrer in 1985; the dominant antimicrobial peptide in human neutrophils and a workhorse molecule of innate immunity. Research peptide only: no defensin has ever been developed as an approved drug.

A 30-amino-acid cationic antimicrobial peptide of the α-defensin subfamily, cleaved from the 94-residue prodefensin encoded by DEFA1/DEFA3, stabilised by three intramolecular disulfide bonds (Cys1-Cys6, Cys2-Cys4, Cys3-Cys5) producing the characteristic triple-stranded β-sheet "defensin fold". HNP-1 was the first human defensin isolated (Ganz, Selsted, Szklarek, Harwig, Daher, Bainton and Lehrer; J Clin Invest, 1985) and remains the most abundant α-defensin in neutrophil azurophilic granules (milligram quantities per 10⁹ cells in combination with HNP-2 and HNP-3, which together constitute roughly 30–50% of azurophilic granule protein).

Mechanism of action

Primary mechanism is direct membrane permeabilisation of microbial targets. The cationic, amphipathic defensin fold binds to anionic bacterial and fungal membrane lipids (lipid II, lipopolysaccharide, lipoteichoic acid, phosphatidylglycerol), then inserts into and destabilises the membrane bilayer — forming transient multimeric pores or disordered patches that dissipate the microbial membrane potential and cause leakage of cytoplasmic contents. HNP-1 has been documented to bind lipid II directly (inhibiting peptidoglycan biosynthesis, like vancomycin does) in addition to its membrane-disrupting activity. Microbicidal spectrum in vitro includes Gram-positive bacteria (S. aureus including MRSA, S. pneumoniae), Gram-negative bacteria (E. coli, P. aeruginosa — though activity is salt-sensitive and can be antagonised by serum), fungi (C. albicans), and enveloped viruses (HSV-1, HIV-1 gp120 binding). Beyond antimicrobial activity, HNP-1 engages multiple host receptors (CCR6-independent chemotaxis of memory T cells and immature dendritic cells, TLR4 activation of antigen-presenting cells, P2Y6 engagement on epithelial cells) and acts as a "alarmin" linking innate to adaptive immunity.

Primary uses

  • Research reagent for antimicrobial peptide studies
  • In-vitro mechanistic research on innate immunity, neutrophil biology, and host-pathogen interaction
  • Biomarker research (sepsis, ulcerative colitis, periodontal disease)
  • Template for rational design of defensin-mimetic antimicrobial drugs (no approved clinical product yet)

Typical dosing

Not established

⚠ No human dosing established. HNP-1 has never been administered as a therapeutic agent. In-vitro microbicidal assays typically use concentrations of 1–100 µg/mL.

Regulatory status

Not a drug. HNP-1 is an endogenous human neutrophil peptide studied as a research reagent for antimicrobial, immunomodulatory, and biomarker purposes. Recombinant and synthetic HNP-1 are available from research vendors (Sigma-Aldrich, Peptides International, Bachem) for in-vitro mechanistic work. Elevated HNP-1/2/3 plasma concentrations have been explored as a biomarker of sepsis, bacterial infection, and inflammatory bowel disease, but no defensin has advanced to regulatory approval as a therapeutic.

References

  1. [pubmed] Ganz T, Selsted ME, Szklarek D, Harwig SS, Daher K, Bainton DF, Lehrer RI. "Defensins. Natural peptide antibiotics of human neutrophils." J Clin Invest, 1985;76(4):1427-1435. (First isolation and naming of HNP-1, -2, -3.)
  2. [review] Lehrer RI, Lu W. "α-Defensins in human innate immunity." Immunol Rev, 2012;245(1):84-112.
  3. [pubmed] de Leeuw E, Li C, Zeng P, et al. "Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II." FEBS Lett, 2010;584(8):1543-1548.

Related peptides

HNP-2

The N-terminally truncated HNP-1 variant — 29 residues instead of 30, same disulfide scaffold, the same biological activity profile. A direct proteolytic or post-translational derivative of the prodefensin encoded by DEFA1/DEFA3; isolated alongside HNP-1 and HNP-3 by Ganz et al. in 1985. Research peptide only — no clinical development.

HNP-3

The third of the three classical neutrophil α-defensins — identical to HNP-1 except the first residue (Asp vs. Ala). Encoded predominantly by DEFA3, a nearly-identical paralog of DEFA1 that arose from segmental duplication. Research peptide only.

HD5

The Paneth cell α-defensin — the dominant antimicrobial peptide of the human small intestine, stored at millimolar concentrations in Paneth cell secretory granules and released into the crypt lumen upon cholinergic or bacterial stimulus. Reduced HD5 expression is a recognised feature of ileal Crohn disease.

HD6

The Paneth cell α-defensin that does not kill directly — HD6 traps enteric pathogens by self-assembling into fibrillar "nanonets" (Chu et al., Science 2012), a mechanism unique among the defensin family. Poor microbicidal activity in vitro was a decade-long puzzle until the trapping mechanism was discovered.

hBD-1

The constitutive epithelial β-defensin — first isolated from haemodialysate urine by Bensch, Schröder and colleagues (FEBS Letters 1995). Constitutively expressed (unlike hBD-2 and hBD-3, which are inducible), salt-sensitive in standard assays, and a major component of urogenital and airway surface antimicrobial defense.

hBD-2

The inducible β-defensin — cloned by Harder, Bartels, Christophers and Schröder (Nature 1997) from the lesional scales of psoriasis patients, with the paper framing psoriatic skin as a paradoxical "almost-never-infected" phenotype driven by massive β-defensin induction. Induced by TLR / NF-κB signalling in response to bacterial lipopolysaccharide and pro-inflammatory cytokines (IL-1, TNF-α).
Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.