Research Only Immune & Anti-Inflammatory

HNP-3

also known as: human neutrophil peptide 3, human α-defensin 3, DEFA3, defensin α3

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.

A 30-amino-acid cationic α-defensin that differs from HNP-1 by a single N-terminal residue substitution — aspartate in place of alanine — and is encoded predominantly by DEFA3, a near-identical paralog of DEFA1 in the DEFA1A3 segmental duplication cluster at chromosome 8p23.1. HNP-3 typically accounts for 10–20% of total HNP content of neutrophil azurophilic granules, with person-to-person variability driven by DEFA1A3 copy number variation.

Mechanism of action

Same mechanism as HNP-1 and HNP-2: cationic membrane permeabilisation, lipid II binding, immunomodulatory and chemotactic activity. The single Ala → Asp N-terminal substitution produces no change in the disulfide-stabilised fold and only marginal changes in microbicidal potency in vitro (HNP-3 is very slightly less potent than HNP-1 against some Gram-negative targets because the negatively charged aspartate reduces the net cationic charge from +4 to +3).

Primary uses

  • Research reagent for antimicrobial peptide studies
  • Biomarker research (HNP-1–3 quantification pool) in infection and inflammation
  • Population-genetics research on DEFA1A3 copy number variation and infection susceptibility

Typical dosing

Not established

⚠ No human dosing established. HNP-3 has never been administered as a therapeutic agent.

Regulatory status

Not a drug. HNP-3 is an endogenous human neutrophil peptide studied as a research reagent. The N-terminal aspartate of HNP-3 introduces a small functional difference — HNP-3 tends to be very slightly less potent than HNP-1 in some in-vitro microbicidal assays, attributed to the acidic N-terminal residue partially neutralising the cationic character that drives membrane binding — but the difference is marginal and clinically irrelevant.

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.
  2. [pubmed] Aldred PM, Hollox EJ, Armour JA. "Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3." Hum Mol Genet, 2005;14(14):2045-2052.
  3. [review] Lehrer RI, Lu W. "α-Defensins in human innate immunity." Immunol Rev, 2012;245(1):84-112.

Related peptides

HNP-1

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.

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.

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.