ArticleFrontiers in immunology2021
Acute Hemolysis and Heme Suppress Anti-CD40 Antibody-Induced Necro-Inflammatory Liver Disease.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Loss of energy homeostasis contributes to hepatic damage development in sickle cell disease.Molecular metabolism · 2026Article
- One trigger, two fates: hemolysate shapes neutrophil extracellular traps (NETs) formation in a context-dependent manner.Frontiers in immunology · 2026Article
- Stress-NRF2 response axis polarizes tumor macrophages and undermines immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Transcription Factor NRF2 in Shaping Myeloid Cell Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Heme (dys)homeostasis and liver disease.Frontiers in physiology · 2024Review
- Hemorrhage-activated NRF2 in tumor-associated macrophages drives cancer growth, invasion, and immunotherapy resistance.The Journal of clinical investigation · 2023Article
- Antibody-induced erythrophagocyte reprogramming of Kupffer cells prevents anti-CD40 cancer immunotherapy-associated liver toxicity.Journal for immunotherapy of cancer · 2023Article
- Sterile inflammation in liver transplantation.Frontiers in medicine · 2023Review
- Impact of Hemin on Interleukin-21 Levels and Plasma Cells in Transfusion-Dependent Thalassemia with Positive and Negative Allo-Autoantibody.International journal of general medicine · 2023Article
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clearance of red blood cells and hemoproteins is a key metabolic function of macrophages during hemolytic disorders and following tissue injury. Through this archetypical phagocytic function, heme is detoxified and iron is recycled to support erythropoiesis. Reciprocal interaction of heme metabolism and inflammatory macrophage functions may modify disease outcomes in a broad range of clinical conditions. We hypothesized that acute hemolysis and heme induce acute anti-inflammatory signals in liver macrophages. Using a macrophage-driven model of sterile liver inflammation, we showed that phenylhydrazine (PHZ)-mediated acute erythrophagocytosis blocked the anti-CD40 antibody-induced pathway of macrophage activation. This process attenuated the inflammatory cytokine release syndrome and necrotizing hepatitis induced by anti-CD40 antibody treatment of mice. We further established that administration of heme-albumin complexes specifically delivered heme to liver macrophages and replicated the anti-inflammatory effect of hemolysis. The anti-inflammatory heme-signal was induced in macrophages by an increased intracellular concentration of the porphyrin independently of iron. Overall, our work suggests that induction of heme-signaling strongly suppresses inflammatory macrophage function, providing protection against sterile liver inflammation.
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Registered trials
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