ArticleAmerican journal of respiratory cell and molecular biology2013
Hemoglobin-induced endothelial cell permeability is controlled, in part, via a myeloid differentiation primary response gene-88-dependent signaling mechanism.
Article in American journal of respiratory cell and molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Extracellular Hemoglobin, Hypoxia, and Macrophage-Mediated Pulmonary Vascular Remodeling in Hemolytic Disease.International journal of molecular sciences · 2026Review
- Emerging links between TLR4 signaling and ferroptosis in heart failure.Frontiers in pharmacology · 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
- Temporal immune profiling in the cerebrospinal fluid and blood of patients with aneurysmal subarachnoid hemorrhage.Journal of leukocyte biology · 2025Article
- Temporal Immune Profiling in the CSF and Blood of Patients with Aneurysmal Subarachnoid Hemorrhage.medRxiv : the preprint server for health sciences · 2024Article
- Potential of acetaminophen on the sublingual microcirculation and peripheral tissue perfusion of febrile septic patients: prospective observational study.Annals of intensive care · 2024Article
- Red blood cell count in cerebrospinal fluid was correlated with inflammatory markers on the seventh postoperative day and all associated with the outcome of aneurysmal subarachnoid hemorrhage patients.Frontiers in medicine · 2024Article
- The Role of the NF-kB Pathway in Intracranial Aneurysms.Brain sciences · 2023Review
- Systemic Inflammation after Aneurysmal Subarachnoid Hemorrhage.International journal of molecular sciences · 2023Review
- Erythrocyte oxidative stress and thrombosis.Expert reviews in molecular medicine · 2022Review
- Potential Role of Soluble Toll-like Receptors 2 and 4 as Therapeutic Agents in Stroke and Brain Hemorrhage.International journal of molecular sciences · 2021Review
- Toxic effects of cell-free hemoglobin on the microvascular endothelium: implications for pulmonary and nonpulmonary organ dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Cell-free hemoglobin-mediated human lung microvascular endothelial barrier dysfunction is not mediated by cell death.Biochemical and biophysical research communications · 2021Article
- Interleukin-31 and Pruritic Skin.Journal of clinical medicine · 2021Review
- Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs in Venous Thrombosis.International journal of molecular sciences · 2020Review
- Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury.JCI insight · 2018Article
- Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin.Biochemical and biophysical research communications · 2018Article
- Unique Contribution of Haptoglobin and Haptoglobin Genotype in Aneurysmal Subarachnoid Hemorrhage.Frontiers in physiology · 2018Review
- Dynamic interactions of Plasmodium spp. with vascular endothelium.Tissue barriers · 2017Review
- Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The release of hemoglobin (Hb) with hemolysis causes vascular dysfunction. New evidence implicates Hb-induced NF-κB and hypoxia inducible factor (HIF) activation, which may be under the control of a Toll-like receptor (TLR)-signaling pathway. Nearly all TLR-signaling pathways activate the myeloid differentiation primary response gene-88 (MyD88) that regulates NF-κB. We hypothesized that the differing transition states of Hb influence endothelial cell permeability via NF-κB activation and HIF regulation through a MyD88-dependent pathway. In cultured human dermal microvascular endothelial cells (HMECs-1), we examined the effects of Hb in the ferrous (HbFe(2+)), ferric (HbFe(3+)), and ferryl (HbFe(4+)) transition states on NF-κB and HIF activity, HIF-1α and HIF-2α mRNA up-regulation, and monolayer permeability, in the presence or absence of TLR4, MyD88, NF-κB, or HIF inhibition, as well as superoxide dismutase (SOD) and catalase. Our data showed that cell-free Hb, in each transition state, induced NF-κB and HIF activity, up-regulated HIF-1α and HIF-2α mRNA, and increased HMEC-1 permeability. The blockade of either MyD88 or NF-κB, but not TLR4, attenuated Hb-induced HIF activity, the up-regulation HIF-1 and HIF-2α mRNA, and HMEC-1 permeability. The inhibition of HIF activity exerted less of an effect on Hb-induced monolayer permeability. Moreover, SOD and catalase attenuated NF-κB, HIF activity, and monolayer permeability. Our results demonstrate that Hb-induced NF-κB and HIF are regulated by two mechanisms, either MyD88 activation or Hb transition state-induced ROS formation, that influence HMEC-1 permeability.
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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.