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Neutrophil activation by heme: implications for inflammatory processes
- Source :
- Blood. 99:4160-4165
- Publication Year :
- 2002
- Publisher :
- American Society of Hematology, 2002.
-
Abstract
- Heme, a ubiquitous iron-containing compound, is present in large amounts in many cells and is inherently dangerous, particularly when it escapes from intracellular sites. The release of heme from damaged cells and tissues is supposed to be higher in diseases such as malaria and hemolytic anemia or in trauma and hemorrhage. We investigated here the role of free ferriprotoporphyrin IX (hemin) as a proinflammatory molecule, with particular attention to its ability to activate neutrophil responses. Injecting hemin into the rat pleural cavity resulted in a dose-dependent migration of neutrophils, indicating that hemin is able to promote the recruitment of these cells in vivo. In vitro, hemin induced human neutrophil chemotaxis and cytoskeleton reorganization, as revealed by the increase of neutrophil actin polymerization. Exposure of human neutrophils to 3 μM hemin activated the expression of the chemokine interleukin-8, as demonstrated by quantitative reverse-transcription polymerase chain reaction, indicating a putative molecular mechanism by which hemin induces chemotaxis in vivo. Brief incubation of human neutrophils with micromolar concentrations of hemin (1-20 μM) triggered the oxidative burst, and the production of reactive oxygen species was directly proportional to the concentration of hemin added to the cells. Finally, we observed that human neutrophil protein kinase C was activated by hemin in vitro, with a K1/2 of 5 μM. Taken together, these results suggest a role for hemin as a proinflammatory agent able to induce polymorphonuclear neutrophil activation in situations of clinical relevance, such as hemolysis or hemoglobinemia.
- Subjects :
- Male
Chemokine
Transcription, Genetic
Neutrophils
Immunology
Heme
In Vitro Techniques
Granulocyte
Biochemistry
Proinflammatory cytokine
chemistry.chemical_compound
Superoxides
polycyclic compounds
medicine
Animals
Interleukin 8
Rats, Wistar
Pleurisy
Cytoskeleton
Protein Kinase C
Respiratory Burst
Inflammation
biology
Reverse Transcriptase Polymerase Chain Reaction
Interleukin-8
Chemotaxis
Cell Biology
Hematology
Actins
Rats
Respiratory burst
Cell biology
Enzyme Activation
Chemotaxis, Leukocyte
medicine.anatomical_structure
chemistry
biology.protein
Hemin
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....52d647321de5b8bebf141d0030d974bb