Iodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway.

Hdl Handle:
http://hdl.handle.net/10147/209014
Title:
Iodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway.
Authors:
Fanning, N F; Manning, B J; Buckley, J; Redmond, H P
Affiliation:
Department of Radiology, Cork University Hospital, Wilton, Cork, Ireland.
Citation:
Br J Radiol. 2002 Nov;75(899):861-73.
Journal:
The British journal of radiology
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209014
PubMed ID:
12466250
Abstract:
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 (p<0.01) apoptotic effect than non-ionic ICM (p<0.05). 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; p<0.05). 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.
Language:
eng
MeSH:
Adult; Apoptosis/*drug effects/physiology; Caspases/*physiology; Cell Culture Techniques/methods; Contrast Media/*pharmacology; Dose-Response Relationship, Drug; Humans; Iodine Compounds/*pharmacology; Mitochondria/physiology; Mitogen-Activated Protein Kinases/physiology; Neutrophil Activation; Neutrophils/*drug effects/physiology; Signal Transduction/drug effects; p38 Mitogen-Activated Protein Kinases
ISSN:
0007-1285 (Print); 0007-1285 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorFanning, N Fen_GB
dc.contributor.authorManning, B Jen_GB
dc.contributor.authorBuckley, Jen_GB
dc.contributor.authorRedmond, H Pen_GB
dc.date.accessioned2012-02-03T15:09:57Z-
dc.date.available2012-02-03T15:09:57Z-
dc.date.issued2012-02-03T15:09:57Z-
dc.identifier.citationBr J Radiol. 2002 Nov;75(899):861-73.en_GB
dc.identifier.issn0007-1285 (Print)en_GB
dc.identifier.issn0007-1285 (Linking)en_GB
dc.identifier.pmid12466250en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209014-
dc.description.abstractIodinated 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 (p<0.01) apoptotic effect than non-ionic ICM (p<0.05). 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; p<0.05). 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshApoptosis/*drug effects/physiologyen_GB
dc.subject.meshCaspases/*physiologyen_GB
dc.subject.meshCell Culture Techniques/methodsen_GB
dc.subject.meshContrast Media/*pharmacologyen_GB
dc.subject.meshDose-Response Relationship, Drugen_GB
dc.subject.meshHumansen_GB
dc.subject.meshIodine Compounds/*pharmacologyen_GB
dc.subject.meshMitochondria/physiologyen_GB
dc.subject.meshMitogen-Activated Protein Kinases/physiologyen_GB
dc.subject.meshNeutrophil Activationen_GB
dc.subject.meshNeutrophils/*drug effects/physiologyen_GB
dc.subject.meshSignal Transduction/drug effectsen_GB
dc.subject.meshp38 Mitogen-Activated Protein Kinasesen_GB
dc.titleIodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway.en_GB
dc.contributor.departmentDepartment of Radiology, Cork University Hospital, Wilton, Cork, Ireland.en_GB
dc.identifier.journalThe British journal of radiologyen_GB
dc.description.provinceMunster-
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