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Cited by 148Antimicrobial Peptides and ActivitiesWound Healing and TreatmentsNeutrophil, Myeloperoxidase and Oxidative Mechanisms

The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.

Inhibition of neutrophil elastase prevents cathelicidin activation and impairs clearance of bacteria from wounds

Cole, Alexander M., Shi, Jishu, Ceccarelli, Alejandro, Kim, Yong-Hwan, Park, Albert, Ganz, Tomas·2001·Blood
DOI 10.1182/blood.v97.1.297
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Abstract

The host defense roles of neutrophil elastase in a porcine skin wound chamber model were explored. Analysis of wound fluid by acid-urea polyacrylamide gel electrophoresis, Western blot, and bacterial overlay confirmed that the neutrophil-derived protegrins constituted the major stable antimicrobial polypeptide in the wound fluid. The application to the wound of 0.10 and 0.25 mM N-methoxysuccinyl-alanine-alanine-proline-valine (AAPV) chloromethyl ketone, a specific neutrophil elastase inhibitor (NEI), blocked the proteolytic activation of protegrins and diminished the associated antimicrobial activity as detected by radial diffusion assay againstStaphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans or by bacterial gel overlay against S epidermidis and E coli. The application of the related cathepsin G inhibitor (CGI), benzyloxycarbonyl-glycine-leucine-phenylalanine (ZGLF) chloromethyl ketone, had no effect. In wound chambers that received 106 colony-forming unit (CFU)/mL of S epidermidis, the presence of NEI significantly decreased the 24-hour clearance of bacteria from the wound compared to wounds treated with CGI or solvent only. Neither inhibitor, at 0.10 or 0.25 mM concentration, affected leukocyte accumulation or degranulation in the wound chambers. The in vitro microbicidal decrement due to NEI was restored by an amount of the specific protegrin (PG-1), which was equivalent to the measured difference of protegrin between control and inhibited chambers. Administration of 1 μg/mL exogenous PG-1 4 hours after chamber preparation was sufficient to normalize in vivo antimicrobial activity. Although pharmacologic NEIs are promising candidates as anti-inflammatory drugs, they may impair host defense in part by inhibiting the activation of cathelicidins by neutrophil elastase.

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Research works printed but not linked: 3

  1. Strukelj, 1995, Molecular cloning and identification of a novel porcine cathelin-like antibacterial peptide precursor., Biol Chem Hoppe Seyler., 376, 507
  2. Harwig, 1995, Prophenin-1, an exceptionally proline-rich antimicrobial peptide from porcine leukocytes., FEBS Lett., 362, 65, 10.1016/0014-5793(95)00210-Z · DOI
  3. Tossi, 1995, PMAP-37, a novel antibacterial peptide from pig myeloid cells: cDNA cloning, chemical synthesis and activity., Eur J Biochem., 228, 941, 10.1111/j.1432-1033.1995.tb20344.x · DOI

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Metadata

Authors
Cole, A. M., Shi, J., Ceccarelli, A., Kim, Y.-H., Park, A., & Ganz, T.
Affiliations
University of California, Los Angeles (US)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2001-01-01
Volume
97
Issue
1
Pages
297-304
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v97.1.297
OpenAlex
W2021030655
Semantic Scholar
10f29c71487573d9f2cc5f55299658f31deb22fe
Cited by
146
References
50
Citations by year
2026: 2 · 2025: 6 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 8 · 2012: 3
FWCI
9.90
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL046809, HL46809, F32HL010181, HL10181)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Health Sciences › Medicine › Surgery › Wound Healing and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
neutrophil elastase, protegrins, wound infection, bacterial clearance, wound fluid, antimicrobial peptides, Staphylococcus epidermidis, Escherichia coli, cathepsin G, host defense, skin wound infection
MeSH terms
Animals, Anti-Bacterial Agents, Bacteria, Body Fluids, Cathepsins, Dose-Response Relationship, Drug, Microbial Sensitivity Tests, Proteins, Serine Endopeptidases, Superoxides, Swine, Wounds and Injuries, Serine Proteinase Inhibitors, Serpins, Leukocyte Elastase, Neutrophil Infiltration, Antimicrobial Cationic Peptides, Models, Animal, Cathelicidins, Cathepsin G

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