ArticleMediators of inflammation2013
Proinflammatory responses of heme in alveolar macrophages: repercussion in lung hemorrhagic episodes.
Article in Mediators of inflammation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Microfluidics-enabled proteomic profiling reveal iron-driven immune evasion by an antimicrobial-resistant pathogen.Cell reports methods · 2026Article
- Redox signaling in chronic airway diseases: pathogenic mechanisms and therapeutic implications.Frontiers in physiology · 2026Review
- From Deficiency to Therapy: Systemic Consequences of ALAS1 Disruption and the Protective Role of 5-ALA.Life (Basel, Switzerland) · 2025Review
- Crosstalk between Inflammation and Hemorrhage/Coagulation Disorders in Primary Blast Lung Injury.Biomolecules · 2023Review
- Vasculo-toxic and pro-inflammatory action of unbound haemoglobin, haem and iron in transfusion-dependent patients with haemolytic anaemias.British journal of haematology · 2021Article
- Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease.Respiratory research · 2021Review
- Heme Induces IL-6 and Cardiac Hypertrophy Genes Transcripts in Sickle Cell Mice.Frontiers in immunology · 2020Article
- Role of Heme Oxygenase as a Modulator of Heme-Mediated Pathways.Antioxidants (Basel, Switzerland) · 2019Review
- Iron Homeostasis in the Lungs-A Balance between Health and Disease.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Heme and hemoglobin suppress amyloid β-mediated inflammatory activation of mouse astrocytes.The Journal of biological chemistry · 2018Article
- Article
- Hemolysis-induced lethality involves inflammasome activation by heme.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- The pathophysiology of extracellular hemoglobin associated with enhanced oxidative reactions.Frontiers in physiology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical and experimental observations have supported the notion that free heme released during hemorrhagic and hemolytic episodes may have a major role in lung inflammation. With alveolar macrophages (AM) being the main line of defense in lung environments, the influence of free heme on AM activity and function was investigated. We observed that heme in a concentration range found during hemolytic episodes (3-30 μM) elicits AM to present a proinflammatory profile, stimulating reactive oxygen species (ROS) and nitric oxide (NO) generation and inducing IL-1β, IL-6, and IL-10 secretion. ROS production is NADPH oxidase-dependent, being inhibited by DPI and apocynin, and involves p47 subunit phosphorylation. Furthermore, heme induces NF- κB nuclear translocation, iNOS, and also HO-1 expression. Moreover, AM stimulated with free heme show enhanced phagocytic and bactericidal activities. Taken together, the data support a dual role for heme in the inflammatory response associated with lung hemorrhage, acting as a proinflammatory molecule that can either act as both an adjuvant of the innate immunity and as an amplifier of the inflammatory response, leading tissue injury. The understanding of heme effects on pulmonary inflammatory processes can lead to the development of new strategies to ameliorate tissue damage associated with hemorrhagic episodes.
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Registered trials
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