Haemolytic uraemic syndrome (HUS) is the major complication of Escherichia coli gastrointestinal infections that are Shiga toxin (Stx) producing. Monocytes contribute to HUS evolution by producing cytokines that sensitize endothelial cells to Stx action and migration to the injured kidney. As CC chemokine receptors (CCRs) are involved in monocyte recruitment to injured tissue, we analysed the contribution of these receptors to the pathogenesis of HUS. We analysed CCR1, CCR2 and CCR5 expression in peripheral monocytes from HUS patients during the acute period, with healthy children as controls. We observed an increased expression of CCRs per cell in monocytes from HUS patients, accompanied by an increase in the absolute number of monocytes CCR1+, CCR2+ and CCR5+. It is interesting that prospective analysis confirmed that CCR1 expression positively correlated with HUS severity. The evaluation of chemokine levels in plasma showed that regulated on activation of normal T-cell-expressed and -secreted (RANTES) protein was reduced in plasma from patients with severe HUS, and this decrease correlated with thrombocytopenia. Finally, the expression of the higher CCRs was accompanied by a loss of functionality which could be due to a mechanism for desensitization to compensate for altered receptor expression. The increase in CCR expression correlates with HUS severity, suggesting that the dysregulation of these receptors might contribute to an increased risk of renal damage. Activated monocytes could be recruited by chemokines and then receptors could be dysregulated. The dysregulation of CCRs and their ligands observed during the acute period suggests that a chemokine pathway would participate in HUS development.
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Research Article|
May 08 2015
Association of haemolytic uraemic syndrome with dysregulation of chemokine receptor expression in circulating monocytes
Maria Victoria Ramos;
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina
Correspondence: María Victoria Ramos (email: mvramos@hematologia.anm.edu.ar).
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Matias Ruggieri;
Matias Ruggieri
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina
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Analia Cecilia Panek;
Analia Cecilia Panek
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina
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Maria Pilar Mejias;
Maria Pilar Mejias
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina
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Romina Jimena Fernandez-Brando;
Romina Jimena Fernandez-Brando
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina
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Maria Jimena Abrey-Recalde;
Maria Jimena Abrey-Recalde
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina
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Andrea Exeni;
Andrea Exeni
†Departamento de Nefrología, Hospital Municipal del Niño, San Justo, Provincia de Buenos Aires, Argentina
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Catalina Barilari;
Catalina Barilari
†Departamento de Nefrología, Hospital Municipal del Niño, San Justo, Provincia de Buenos Aires, Argentina
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Ramon Exeni;
Ramon Exeni
†Departamento de Nefrología, Hospital Municipal del Niño, San Justo, Provincia de Buenos Aires, Argentina
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Marina Sandra Palermo
Marina Sandra Palermo
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina
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Publisher: Portland Press Ltd
Received:
January 07 2015
Revision Received:
March 02 2015
Accepted:
March 06 2015
Accepted Manuscript online:
March 06 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 129 (3): 235–244.
Article history
Received:
January 07 2015
Revision Received:
March 02 2015
Accepted:
March 06 2015
Accepted Manuscript online:
March 06 2015
Citation
Maria Victoria Ramos, Matias Ruggieri, Analia Cecilia Panek, Maria Pilar Mejias, Romina Jimena Fernandez-Brando, Maria Jimena Abrey-Recalde, Andrea Exeni, Catalina Barilari, Ramon Exeni, Marina Sandra Palermo; Association of haemolytic uraemic syndrome with dysregulation of chemokine receptor expression in circulating monocytes. Clin Sci (Lond) 1 August 2015; 129 (3): 235–244. doi: https://doi.org/10.1042/CS20150016
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