Evidence map›Paper›PMID 19581399›Full record

ArticleInfection and immunity2009

Human alpha-defensins inhibit hemolysis mediated by cholesterol-dependent cytolysins.

Robert I Lehrer, Grace Jung, Piotr Ruchala, Wei Wang, Ewa D Micewicz, Alan J Waring, Eugene J Gillespie, Kenneth A Bradley, Adam J Ratner, Richard F Rest and 1 more

Abstract read
In one paragraph

Article in Infection and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.7field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 56 citations in OpenAlex.

  1. Review
  2. Capsule and PspA Cooperatively Confer Resistance ofInternational journal of molecular sciences · 2026
    Article
  3. Effects of Bile on PathogenicBiomolecules · 2025
    Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Human α-Defensin-5 Efficiently NeutralizesFrontiers in pharmacology · 2020
    Article
  11. Review
  12. Review
  13. Article
  14. Listeriolysin O: from bazooka to Swiss army knife.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017
    Review
  15. Article
  16. Bacterial Virulence Factors: Secreted for Survival.Indian journal of microbiology · 2017
    Review
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Robert I LehrerDepartment of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. rlehrer@mednet.ucla.edu
Grace Jung
Piotr Ruchala
Wei Wang
Ewa D Micewicz
Alan J Waring
Eugene J Gillespie
Kenneth A Bradley
Adam J Ratner
Richard F Rest
Wuyuan Lu
University of California, Los Angeles · USColumbia University · USDrexel University · USUniversity of Maryland, Baltimore · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many pathogenic gram-positive bacteria release exotoxins that belong to the family of cholesterol-dependent cytolysins. Here, we report that human alpha-defensins HNP-1 to HNP-3 acted in a concentration-dependent manner to protect human red blood cells from the lytic effects of three of these exotoxins: anthrolysin O (ALO), listeriolysin O, and pneumolysin. HD-5 was very effective against listeriolysin O but less effective against the other toxins. Human alpha-defensins HNP-4 and HD-6 and human beta-defensin-1, -2, and -3 lacked protective ability. HNP-1 required intact disulfide bonds to prevent toxin-mediated hemolysis. A fully linearized analog, in which all six cysteines were replaced by aminobutyric acid (Abu) residues, showed greatly reduced binding and protection. A partially unfolded HNP-1 analog, in which only cysteines 9 and 29 were replaced by Abu residues, showed intact ALO binding but was 10-fold less potent in preventing hemolysis. Surface plasmon resonance assays revealed that HNP-1 to HNP-3 bound all three toxins at multiple sites and also that solution-phase HNP molecules could bind immobilized HNP molecules. Defensin concentrations that inhibited hemolysis by ALO and listeriolysin did not prevent these toxins from binding either to red blood cells or to cholesterol. Others have shown that HNP-1 to HNP-3 inhibit lethal toxin of Bacillus anthracis, toxin B of Clostridium difficile, diphtheria toxin, and exotoxin A of Pseudomonas aeruginosa; however, this is the first time these defensins have been shown to inhibit pore-forming toxins. An "ABCDE mechanism" that can account for the ability of HNP-1 to HNP-3 to inhibit so many different exotoxins is proposed.

Indexed as

alpha-DefensinsAmino Acid SequenceAnimalsBacterial ProteinsBacterial ToxinsCholesterolElectrophoresis, Polyacrylamide GelEnzyme-Linked Immunosorbent AssayHeat-Shock ProteinsHemolysin ProteinsHemolysisHumansHydrogen-Ion ConcentrationMembrane GlycoproteinsMolecular Sequence DataRabbitsalpha-Defensinsanthrolysin O, Bacillus anthracisBacterial ProteinsBacterial ToxinsCholesterolHeat-Shock ProteinsHemolysin ProteinshlyA protein, Listeria monocytogenesMembrane GlycoproteinsplY protein, Streptococcus pneumoniaeStreptolysins

Identifiers

PMID19581399
PMCPMC2738040
OpenAlexW2011749795

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.