Heme Induces Neutrophil Migration and Reactive Oxygen Species Generation through Signaling Pathways Characteristic of Chemotactic Receptors
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Hemolysis or extensive cell damage can lead to high concentrations of free heme, causing oxidative stress and inflammation. Considering that heme induces neutrophil chemotaxis, we hypothesize that heme activates a G protein-coupled receptor. Here we show that similar to heme, several heme analogs were able to induce neutrophil migration in vitro and in vivo. Mesoporphyrins, molecules lacking the vinyl groups in their rings, were not chemotactic for neutrophils and selectively inhibited heme-induced migration. Moreover, migration of neutrophils induced by heme was abolished by pretreatment with pertussis toxin, an inhibitor of Galpha inhibitory protein, and with inhibitors of phosphoinositide 3-kinase, phospholipase Cbeta, mitogen-activated protein kinases, or Rho kinase. The induction of reactive oxygen species by heme was dependent of Galpha inhibitory protein and phosphoinositide 3-kinase and partially dependent of phospholipase Cbeta, protein kinase C, mitogen-activated protein kinases, and Rho kinase. Together, our results indicate that heme activates neutrophils through signaling pathways that are characteristic of chemoattractant molecules and suggest that mesoporphyrins might prove valuable in the treatment of the inflammatory consequences of hemorrhagic and hemolytic disorders.
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Labile heme exerts chemotactic effects via activation of G protein-coupled receptors in PMN cells.
“Labile heme also exerts chemotactic effects via the activation of G protein-coupled receptors expressed in PMN cells [207], while promoting the release of neutrophil extracellular traps (NETs) from activated PMN cells [208] (Fig 4).”
From The Iron age of host–microbe interactions (2015) · cites this paper as [207]
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- Authors
- Porto, B. N., Alves, L. S., Fernández, P. L., Dutra, T. P., Figueiredo, R. T., Graça-Souza, A. V., & Bozza, M. T.
- Affiliations
- Universidade Federal do Rio de Janeiro (BR)
- Corresponding author
- Bozza, Marcelo T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 282
- Issue
- 33
- Pages
- 24430-24436
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2058844821
- Cited by
- 161
- References
- 33
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 14 · 2020: 7 · 2019: 14 · 2018: 11 · 2017: 14 · 2016: 10 · 2015: 11 · 2014: 8 · 2013: 10 · 2012: 8
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Greater South Information System
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- heme, neutrophil migration, reactive oxygen species, G protein-coupled receptors, mesoporphyrin, phosphatidylinositol 3-kinase, phospholipase C beta, mitogen-activated protein kinase, Rho kinase, protein kinase C, oxidative stress, inflammation, hemolysis, hemorrhagic disease, hemolytic disease
- MeSH terms
- Animals, Chemotaxis, Heme, Humans, Mice, Inbred C57BL, Neutrophils, Signal Transduction, Reactive Oxygen Species, Receptors, Chemokine, Neutrophil Infiltration, Mice
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