Evidence map›Paper›PMID 31400851›Full record

ArticleBiochemical and biophysical research communications2019

Benzyloxycarbonyl-proline-prolinal (ZPP): Dual complementary roles for neutrophil inhibition.

D W Russell, M Hardison, K R Genschmer, T Szul, P E Bratcher, M Abdul Roda, X Xu, L Viera, J E Blalock, A Gaggar and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemical and biophysical research communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 48% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Review
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 2 countries.

D W RussellDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA. Electronic address: dwrussell@uabmc.edu.
M HardisonDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
K R GenschmerDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
T SzulDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
P E BratcherDepartment of Pediatrics, National Jewish Health, Denver, CO, 80206, USA.
M Abdul RodaDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Division of Pharmacology, Utrecht Institute for Pharmaceutical Science, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
X XuDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Department of Cell, Developmental, and Integrative Biology, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
L VieraDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Department of Cell, Developmental, and Integrative Biology, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
J E BlalockDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Department of Cell, Developmental, and Integrative Biology, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
A GaggarDepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Department of Cell, Developmental, and Integrative Biology, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Medical Service, Birmingham VA Medical Center Birmingham, AL, 35294, USA.
B D NoeragerUniversity of Montevallo, Montevallo, AL, 35115, USA.
University of Alabama at Birmingham · USNational Jewish Health · USUniversity of Montevallo · USUtrecht University · NL

Funding

A Novel Exosomal Inflammatory PathwayR35HL135710 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BLALOCK, J EDWIN · 2017 to 2023
$6.8M
Training Program in Lung Biology and Translational MedicineT32HL105346 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GAGGAR, AMIT · 2010 to 2025
$5.0M
A Novel Proteolytic System of Pulmonary InflammationR01HL102371 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GAGGAR, AMIT · 2010 to 2021
$3.3M
Genetics of Smoke-Altered LTA4H in COPDR01HL126596 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BLALOCK, J EDWIN, CASTALDI, PETER · 2015 to 2018
$1.6M
NHLBI NIH HHS R01 HL102371NHLBI NIH HHS R01 HL126596NHLBI NIH HHS R35 HL135710NHLBI NIH HHS T32 HL105346
6 · The paper itself

Abstract

Neutrophil influx and activation contributes to organ damage in several major lung diseases. This inflammatory influx is initiated and propagated by both classical chemokines such as interleukin-8 and by downstream mediators such as the collagen fragment cum neutrophil chemokine Pro-Gly-Pro (PGP), which share use of the ELR + CXC receptor family. Benzyloxycarbonyl-proline-prolinal (ZPP) is known to suppress the PGP pathway via inhibition of prolyl endopeptidase (PE), the terminal enzyme in the generation of PGP from collagen. However, the structural homology of ZPP and PGP suggests that ZPP might also directly affect classical glutamate-leucine-arginine positive (ELR+) CXC chemokine signaling. In this investigation, we confirm that ZPP inhibits PE in vitro, demonstrate that ZPP inhibits both ELR + CXC and PGP-mediated chemotaxis in human and murine neutrophils, abrogates neutrophil influx induced by murine intratracheal challenge with LPS, and attenuates human neutrophil chemotaxis to sputum samples of human subjects with cystic fibrosis. Cumulatively, these data demonstrate that ZPP has dual, complementary inhibitory effects upon neutrophil chemokine/matrikine signaling which make it an attractive compound for clinical study of neutrophil inhibition in conditions (such as cystic fibrosis and chronic obstructive pulmonary disease) which evidence concurrent harmful increases of both chemokine and matrikine signaling.

Indexed as

AnimalsChemotaxisHumansInflammationMice, Inbred BALB CModels, MolecularNeutrophilsOligopeptidesProlineSputumbenzyloxycarbonylprolineOligopeptidesprolinalProlineprolyl-glycyl-prolineBenzyloxycarbonyl-proline-prolinalCOPDCXCRPGPProlyl-endopeptidaseZPP

Identifiers

PMID31400851
PMCPMC6730661
OpenAlexW2965192468

What OpenQuestion holds

Textmetadata
LicenceTDM
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.