Evidence map›Paper›PMID 34496918›Full record

ArticleParticle and fibre toxicology2021

Pulmonary delivery of the broad-spectrum matrix metalloproteinase inhibitor marimastat diminishes multiwalled carbon nanotube-induced circulating bioactivity without reducing pulmonary inflammation.

Tamara L Young, Ekaterina Mostovenko, Jesse L Denson, Jessica G Begay, Selita N Lucas, Guy Herbert, Katherine Zychowski, Russell Hunter, Raul Salazar, Ting Wang and 4 more

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

Article in Particle and fibre toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 37% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

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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

14 authors at 4 institutions in 1 country.

Tamara L YoungDepartment of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA.
Ekaterina MostovenkoDepartment of Anatomy and Neurobiology, Virginia Commonwealth University, PO Box 980709, Richmond, VA, 23298, USA.
Jesse L DensonDepartment of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA.
Jessica G BegayDepartment of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA.
Selita N LucasDepartment of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA.
Guy HerbertDepartment of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA.
Katherine ZychowskiCollege of Nursing, University of New Mexico, Albuquerque, NM, 87131, USA.
Russell HunterDepartment of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA.
Raul SalazarDepartment of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA.
Ting WangDepartment of Internal Medicine, University of Arizona College of Medicine, Phoenix, AZ, USA.
Kelly FraserPathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Aaron ErdelyPathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA.
Andrew K OttensDepartment of Anatomy and Neurobiology, Virginia Commonwealth University, PO Box 980709, Richmond, VA, 23298, USA.
Matthew J CampenDepartment of Pharmaceutical Sciences, MSC09 5360, 1 University of New Mexico, Albuquerque, NM, 87131-0001, USA. MCampen@salud.unm.edu.ORCID 0000-0002-2292-5050
University of New Mexico · USNational Institute for Occupational Safety and Health · USVirginia Commonwealth University · USUniversity of Arizona · US

Funding

Systemic Health Implications of Occupational Nanomaterial ExposureR01OH010828 · OH · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI CAMPEN, MATTHEW J, OTTENS, ANDREW K · 2015 to 2018
$1.9M
ACL HHS R01OH010828NIOSH CDC HHS R01 OH010828
6 · The paper itself

Abstract

backgroundMultiwalled carbon nanotubes (MWCNT) are an increasingly utilized engineered nanomaterial that pose the potential for significant risk of exposure-related health outcomes. The mechanism(s) underlying MWCNT-induced toxicity to extrapulmonary sites are still being defined. MWCNT-induced serum-borne bioactivity appears to dysregulate systemic endothelial cell function. The serum compositional changes after MWCNT exposure have been identified as a surge of fragmented endogenous peptides, likely derived from matrix metalloproteinase (MMP) activity. In the present study, we utilize a broad-spectrum MMP inhibitor, Marimastat, along with a previously described oropharyngeal aspiration model of MWCNT administration to investigate the role of MMPs in MWCNT-derived serum peptide generation and endothelial bioactivity.

resultsC57BL/6 mice were treated with Marimastat or vehicle by oropharyngeal aspiration 1 h prior to MWCNT treatment. Pulmonary neutrophil infiltration and total bronchoalveolar lavage fluid protein increased independent of MMP blockade. The lung cytokine profile similarly increased following MWCNT exposure for major inflammatory markers (IL-1β, IL-6, and TNF-α), with minimal impact from MMP inhibition. However, serum peptidomic analysis revealed differential peptide compositional profiles, with MMP blockade abrogating MWCNT-derived serum peptide fragments. The serum, in turn, exhibited differential potency in terms of inflammatory bioactivity when incubated with primary murine cerebrovascular endothelial cells. Serum from MWCNT-treated mice led to inflammatory responses in endothelial cells that were significantly blunted with serum from Marimastat-treated mice.

conclusionsThus, MWCNT exposure induced pulmonary inflammation that was largely independent of MMP activity but generated circulating bioactive peptides through predominantly MMP-dependent pathways. This MWCNT-induced lung-derived bioactivity caused pathological consequences of endothelial inflammation and barrier disruption.

Indexed as

Nanotubes, CarbonPneumoniaAnimalsBronchoalveolar Lavage FluidEndothelial CellsHydroxamic AcidsLungMatrix Metalloproteinase InhibitorsMiceMice, Inbred C57BLHydroxamic AcidsmarimastatMatrix Metalloproteinase InhibitorsNanotubes, CarbonBiomarkerCarbon nanotubesInflammationMatrix metalloproteinaseMultiwall carbon nanotube (MWCNT)NanomaterialsNanoparticlesSerum-bioactivity

Identifiers

PMID34496918
PMCPMC8424988
OpenAlexW3198063210

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.