Evidence map›Paper›PMID 32012200›Full record

ArticlePloS one2020

Cell-free hemoglobin increases inflammation, lung apoptosis, and microvascular permeability in murine polymicrobial sepsis.

Jamie E Meegan, Ciara M Shaver, Nathan D Putz, Jordan J Jesse, Stuart R Landstreet, Han Noo Ri Lee, Tatiana N Sidorova, J Brennan McNeil, James L Wynn, Joyce Cheung-Flynn and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
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  10. The long road to Ithaca: a physiologist's journey.American journal of physiology. Cell physiology · 2025
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  14. Review
  15. Hemopexin reverses activation of lung eIF2α and decreases mitochondrial injury in chlorine-exposed mice.American journal of physiology. Lung cellular and molecular physiology · 2024
    Article
  16. Article
  17. Article
  18. Review
  19. Article
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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 3 institutions in 1 country.

Jamie E MeeganDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.ORCID 0000-0002-2644-676X
Ciara M ShaverDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Nathan D PutzDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Jordan J JesseDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Stuart R LandstreetDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Han Noo Ri LeeDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Tatiana N SidorovaDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
J Brennan McNeilDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
James L WynnDepartments of Pediatrics, Pathology, Immunology, and Experimental Medicine, University of Florida Health, Gainesville, FL, United States of America.
Joyce Cheung-FlynnDivision of Vascular Surgery, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Padmini KomalavilasDivision of Vascular Surgery, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Colleen M BrophyDivision of Vascular Surgery, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Lorraine B WareDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
Julie A BastaracheDivision of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.ORCID 0000-0003-0458-6507
Vanderbilt University Medical Center · USUniversity of Florida Health · USVanderbilt University · US

Funding

PREVENTION OF VEIN GRAFT SPASMR01HL070715 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BROPHY, COLLEEN M · 2003 to 2021
$7.2M
Interdisciplinary Training Program in Lung ResearchT32HL094296 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ray Stokes Peebles · 2008 to 2026
$6.3M
Microfluidic Assessment of Clinical Outcomes in Preterm NewbornsR01HD089939 · NICHD · UNIVERSITY OF FLORIDA · PI IRIMIA, DANIEL, MOLDAWER, LYLE L · 2017 to 2021
$3.3M
Targeting cell-free hemoglobin in sepsis to reduce lung microvascular permeability: mechanistic and translational studiesR01HL135849 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BASTARACHE, JULIE ANNE, WARE, LORRAINE B · 2017 to 2020
$2.2M
Modifiable Determinants of Mortality in Neonatal SepsisR01GM128452 · NIGMS · UNIVERSITY OF FLORIDA · PI WYNN, JAMES LAWRENCE · 2018 to 2022
$1.9M
Midcareer Investigator Award in Patient-Oriented Research in Acute Lung InjuryK24HL103836 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WARE, LORRAINE B · 2010 to 2020
$1.6M
Mechanisms of airspace inflammation caused by cell-free hemoglobin during ARDSK08HL136888 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SHAVER, CIARA M · 2017 to 2021
$858k
Leica Bond RXS10OD023475 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BOYD, KELLI L. · 2018 to 2018
$213k
NHLBI NIH HHS K08 HL136888NHLBI NIH HHS K24 HL103836NHLBI NIH HHS R01 HL070715NHLBI NIH HHS R01 HL135849NHLBI NIH HHS T32 HL094296NICHD NIH HHS R01 HD089939NIGMS NIH HHS R01 GM128452NIH HHS S10 OD023475
6 · The paper itself

Abstract

Increased endothelial permeability is central to the pathogenesis of sepsis and leads to organ dysfunction and death but the endogenous mechanisms that drive increased endothelial permeability are not completely understood. We previously reported that cell-free hemoglobin (CFH), elevated in 80% of patients with sepsis, increases lung microvascular permeability in an ex vivo human lung model and cultured endothelial cells. In this study, we augmented a murine model of polymicrobial sepsis with elevated circulating CFH to test the hypothesis that CFH increases microvascular endothelial permeability by inducing endothelial apoptosis. Mice were treated with an intraperitoneal injection of cecal slurry with or without a single intravenous injection of CFH. Severity of illness, mortality, systemic and lung inflammation, endothelial injury and dysfunction and lung apoptosis were measured at selected time points. We found that CFH added to CS increased sepsis mortality, plasma inflammatory cytokines as well as lung apoptosis, edema and inflammation without affecting large vessel reactivity or vascular injury marker concentrations. These results suggest that CFH is an endogenous mediator of increased endothelial permeability and apoptosis in sepsis and may be a promising therapeutic target.

Indexed as

ApoptosisCapillary PermeabilityAnimalsEndothelial CellsFemaleHemoglobinsHumansInflammationLungMiceMice, Inbred C57BLOxidative StressSepsisHemoglobins

Identifiers

PMID32012200
PMCPMC6996826
OpenAlexW3004171702

What Socratic holds

Textmetadata
LicenceCC0
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.