Iodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway.
AffiliationDepartment of Radiology, Cork University Hospital, Wilton, Cork, Ireland.
Cell Culture Techniques/methods
Dose-Response Relationship, Drug
Mitogen-Activated Protein Kinases/physiology
Signal Transduction/drug effects
p38 Mitogen-Activated Protein Kinases
MetadataShow full item record
CitationBr J Radiol. 2002 Nov;75(899):861-73.
JournalThe British journal of radiology
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.
- Inhibition of K+ efflux prevents mitochondrial dysfunction, and suppresses caspase-3-, apoptosis-inducing factor-, and endonuclease G-mediated constitutive apoptosis in human neutrophils.
- Authors: El Kebir D, József L, Khreiss T, Filep JG
- Issue date: 2006 Dec
- Activation of human neutrophils by the plant lectin Viscum album agglutinin-I: modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis.
- Authors: Savoie A, Lavastre V, Pelletier M, Hajto T, Hostanska K, Girard D
- Issue date: 2000 Dec
- Inhibition of neutrophil apoptosis via sphingolipid signaling in acute lung injury.
- Authors: Lin WC, Lin CF, Chen CL, Chen CW, Lin YS
- Issue date: 2011 Oct
- Proapoptotic effect of curcumin on human neutrophils: activation of the p38 mitogen-activated protein kinase pathway.
- Authors: Hu M, Du Q, Vancurova I, Lin X, Miller EJ, Simms HH, Wang P
- Issue date: 2005 Nov
- C5a delays apoptosis of human neutrophils via an extracellular signal-regulated kinase and Bad-mediated signalling pathway.
- Authors: Perianayagam MC, Balakrishnan VS, Pereira BJ, Jaber BL
- Issue date: 2004 Jan