Iodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway
| Autor: | N F Fanning, Henry Paul Redmond, James F. Buckley, Brian J. Manning |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Adult
MAPK/ERK pathway Programmed cell death Neutrophils p38 mitogen-activated protein kinases Cell Culture Techniques Iodine Compounds Contrast Media Apoptosis p38 Mitogen-Activated Protein Kinases Neutrophil Activation Flow cytometry Annexin medicine Humans Radiology Nuclear Medicine and imaging reproductive and urinary physiology Caspase Dose-Response Relationship Drug biology medicine.diagnostic_test Chemistry General Medicine equipment and supplies Mitochondria Cell biology Caspases embryonic structures Immunology biology.protein Mitogen-Activated Protein Kinases Intracellular Signal Transduction circulatory and respiratory physiology |
| Zdroj: | The British Journal of Radiology. 75:861-873 |
| ISSN: | 1748-880X 0007-1285 |
| DOI: | 10.1259/bjr.75.899.750861 |
| Popis: | Iodinated contrast media (ICM) can induce apoptosis (programmed cell death) in renal, myocardial and endothelial cells. Following intravascular injection, circulating immune cells are exposed to high concentrations of ICM. As neutrophils constitutively undergo apoptosis we hypothesized that ICM may adversely affect neutrophil survival. Our aim was to investigate the effect of ICM on neutrophil apoptosis. Neutrophils were isolated from healthy subjects and cultured in vitro with ionic (diatrizoate and ioxaglate) and non-ionic (iohexol and iotrolan) ICM. The effect of ICM on neutrophil apoptosis in both unstimulated and lipopolysaccharide-stimulated neutrophils was determined by annexin V flow cytometry. The influence of physicochemical properties of the different ICM on apoptosis of neutrophils was also studied. We further investigated the effects of ICM on key intracellular signal pathways, including p38 mitogen-activated protein kinase (MAPK) by Western blotting, and mitochondrial depolarization and caspase activity by flow cytometry. Isoiodine concentrations (20 mg ml(-1)) of ionic (diatrizoate 69.6+/-2.9%; ioxaglate 58.9+/-2.0%) and non-ionic (iohexol 57.3+/-2.9%; iotrolan 57.1+/-2.6%) ICM significantly induced neutrophil apoptosis over control levels (47.7+/-1.4%). The apoptotic effect of ICM was influenced by their chemical structure, with ionic ICM having a more significant (p0.01) apoptotic effect than non-ionic ICM (p0.05). Furthermore, ICM reversed the anti-apoptotic effect of lipopolysaccharide (1000 ng ml(-1)) treated neutrophils to control levels (23.0+/-3.5% to 61.2+/-5.3%; n=4; p0.05). These agents induce apoptosis through a p38 MAPK independent pathway that results in mitochondrial depolarization, and is dependent on caspase activation. As neutrophils play a central role in host response to infection and injury, ICM, through induction of neutrophil apoptosis, could have a significant deleterious effect on host immune defence and resolution of an inflammatory response. |
| Databáze: | OpenAIRE |
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