Research Only Immune & Anti-Inflammatory

HNP-2

also known as: human neutrophil peptide 2, human α-defensin 2, defensin α2

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.

A 29-amino-acid cationic α-defensin that differs from HNP-1 by the absence of the N-terminal alanine residue; it is generated from the same DEFA1/DEFA3 prodefensin precursor by variant processing rather than from a distinct gene. HNP-2 was co-isolated with HNP-1 and HNP-3 in the landmark 1985 defensin paper and typically accounts for roughly 20–30% of total HNP content of neutrophil azurophilic granules.

Mechanism of action

Mechanism is functionally equivalent to HNP-1: direct cationic membrane permeabilisation of bacterial, fungal and enveloped viral membranes, plus lipid II binding and a range of immunomodulatory activities including chemotaxis of immature dendritic cells and memory T cells. The single N-terminal alanine deletion does not alter the disulfide-stabilised β-sheet fold and produces no consistent change in microbicidal potency in vitro. Because DEFA1 and DEFA3 genes are highly copy-number variable between individuals, the HNP-1 : HNP-2 : HNP-3 ratio in any given person reflects a combination of gene dosage and post-translational processing efficiency rather than regulated differential expression.

Primary uses

  • Research reagent for antimicrobial peptide and neutrophil biology studies
  • Biomarker research (HNP-1–3 pooled quantification) in sepsis, bacterial pneumonia, ulcerative colitis, periodontitis, and graft-versus-host disease
  • Template for defensin-mimetic antimicrobial drug design

Typical dosing

Not established

⚠ No human dosing established. HNP-2 has never been administered as a therapeutic agent. In-vitro microbicidal concentrations parallel HNP-1 (1–100 µg/mL).

Regulatory status

Not a drug. HNP-2 is an endogenous human neutrophil peptide studied primarily as a research reagent. Synthetic and recombinant HNP-2 are available from research vendors. HNP-2 is almost always quantified together with HNP-1 and HNP-3 as "HNP-1–3" in clinical biomarker work because they cannot be resolved by standard ELISA and share essentially identical biology.

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. [review] Ganz T. "Defensins: antimicrobial peptides of innate immunity." Nat Rev Immunol, 2003;3(9):710-720.
  3. [pubmed] Linzmeier RM, Ganz T. "Human defensin gene copy number polymorphisms: comprehensive analysis of independent variation in alpha- and beta-defensin regions at 8p22-p23." Genomics, 2005;86(4):423-430.

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-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.