ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Cell-free hemoglobin: a novel mediator of acute lung injury.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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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.
Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Hemolysis in patients with Extracorporeal Membrane Oxygenation therapy for severe Acute Respiratory Distress Syndrome - a systematic review of the literature.International journal of medical sciences · 2021Pooled it
- Impact of Point-of-care Allogeneic Red Blood Cell Washing on Markers of Transfusion-related Respiratory Complications: A Phase II Randomized Clinical Trial.Anesthesiology · 2025Trial
- Evaluation of Plasma Biomarkers to Understand the Biology and Heterogeneity of Treatment Effect in Lower Tidal Volume Ventilation Facilitated by Extracorporeal CO2 Removal in Acute Hypoxemic Respiratory Failure: A Secondary Analysis of the REST Trial.Critical care explorations · 2025Trial
- Trial
- CD163 protects against pulmonary injury and inflammation induced by acute ObioRxiv : the preprint server for biology · 2026Article
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- Review
- Small Interfering RNA (siRNA) as a Targeted Therapy for Acute Respiratory Distress Syndrome: Evidence from Experimental Models.International journal of molecular sciences · 2026Review
- The Role of Toll-like Receptors and Viral Infections in the Pathogenesis and Progression of Pulmonary Arterial Hypertension-A Narrative Review.International journal of molecular sciences · 2025Review
- Material-Induced Platelet Adhesion/Activation and Hemolysis of Membrane Lung Components from Extracorporeal Membrane Oxygenation.Biomedicines · 2025Article
- Hemolysis and Its Clinical Implications in Septic Patients with Acute Respiratory Failure.Journal of clinical medicine · 2025Article
- Oxidation of low-density lipoprotein by hemoglobin causes pulmonary microvascular endothelial barrier dysfunction through lectin-like oxidized LDL receptor 1.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- The long road to Ithaca: a physiologist's journey.American journal of physiology. Cell physiology · 2025Review
- Heme-induced lung injury in human precision cut lung slices: a new model for acute lung injury.Respiratory research · 2025Article
- Total bilirubin as a marker for hemolysis and outcome in patients with severe ARDS treated with veno-venous ECMO.BMC anesthesiology · 2025Article
- Pilot study: In vitro reduction of hemoglobin from canine blood with hemoperfusion using the Cytosorb® adsorber.PloS one · 2025Article
- Signs of Hemolysis Predict Mortality and Ventilator Associated Pneumonia in Severe Acute Respiratory Distress Syndrome Patients Undergoing Veno-Venous Extracorporeal Membrane Oxygenation.ASAIO journal (American Society for Artificial Internal Organs : 1992) · 2025Article
- Effects of acetaminophen use on mortality of patients with acute respiratory distress syndrome: secondary data mining based on the MIMIC-IV database.BMC pulmonary medicine · 2024Article
- Hemopexin reverses activation of lung eIF2α and decreases mitochondrial injury in chlorine-exposed mice.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Vitamin C: Rationale for Its Use in Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS).Antioxidants (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with the acute respiratory distress syndrome (ARDS) have elevated levels of cell-free hemoglobin (CFH) in the air space, but the contribution of CFH to the pathogenesis of acute lung injury is unknown. In the present study, we demonstrate that levels of CFH in the air space correlate with measures of alveolar-capillary barrier dysfunction in humans with ARDS (r = 0.89, P < 0.001) and in mice with ventilator-induced acute lung injury (r = 0.89, P < 0.001). To investigate the specific contribution of CFH to ARDS, we studied the impact of purified CFH in the mouse lung and on cultured mouse lung epithelial (MLE-12) cells. Intratracheal delivery of CFH in mice causes acute lung injury with air space inflammation and alveolar-capillary barrier disruption. Similarly, in MLE-12 cells, CFH increases proinflammatory cytokine expression and increases paracellular permeability as measured by electrical cell-substrate impedance sensing. Next, to determine whether these effects are mediated by the iron-containing heme moiety of CFH, we treated mice with intratracheal hemin, the chloride salt of heme, and found that hemin was sufficient to increase alveolar permeability but failed to induce proinflammatory cytokine expression or epithelial cell injury. Together, these data identify CFH in the air space as a previously unrecognized driver of lung epithelial injury in human and experimental ARDS and suggest that CFH and hemin may contribute to ARDS through different mechanisms. Interventions targeting CFH and heme in the air space could provide a new therapeutic approach for ARDS.
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Registered trials
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.