Association of haemolytic uraemic syndrome with dysregulation of chemokine receptor expression in circulating monocytes.
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.
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina.
Maria Victoria
MV
Ramos
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina.
Matias
M
Ruggieri
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina.
Analia Cecilia
AC
Panek
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina.
Maria Pilar
MP
Mejias
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina.
Romina Jimena
RJ
Fernandez-Brando
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina.
Maria Jimena
MJ
Abrey-Recalde
†Departamento de Nefrología, Hospital Municipal del Niño, San Justo, Provincia de Buenos Aires, Argentina.
Andrea
A
Exeni
†Departamento de Nefrología, Hospital Municipal del Niño, San Justo, Provincia de Buenos Aires, Argentina.
Catalina
C
Barilari
†Departamento de Nefrología, Hospital Municipal del Niño, San Justo, Provincia de Buenos Aires, Argentina.
Ramon
R
Exeni
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina.
Marina Sandra
MS
Palermo
D002465:Cell Movement; D018925:Chemokines / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D011446:Prospective Studies; D019707:Receptors, Chemokine / Q000378:metabolism*
D018925:Chemokines; D019707:Receptors, Chemokine