Hemolytic Uremic Syndrome is associated with dysregulation of Chemokine Receptor expression in Circulating Monocytes

RAMOS MV ; RUGGIERI M; PANEK CA; MEJIAS MP; FERNANDEZ-BRANDO RJ; ABREY RECALDE MJ; EXENI A; BARILARI C; EXENI R,; PALERMO MS

CLINICAL SCIENCE (LONDON, ENGLAND : 1979)

PORTLAND PRESS LTD

Lugar: Londres; Año: 2015 vol. 129 p. 235 - 244

0143-5221

Hemolytic uremic syndrome (HUS) is the major complication of Shiga toxin (Stx)-producing  Escherichia coli gastrointestinal infections. Monocytes (Mo) contributes to HUS evolution by producing cytokines that sensitize endothelial cells to Stx action and by migrating to injured kidney. Since CC chemokine receptors (CCRs) are involved in Mo recruitment to injured tissue, we analyzed the contribution of these receptors to pathogenesis of HUS.  We analyzed CCR1, CCR2 and CCR5 in Mo from HUS patients during the acute period, and healthy children as controls. We observed an increased expression per cell of CCRs in Mo from HUS patients, accompanied by an increase in the absolute number of Mo CCR1+, CCR2+ and CCR5+. Interestingly prospective analysis confirmed that CCR1 expression positively correlated with HUS severity. Plasmatic chemokines levels showed that RANTES, was reduced in plasma from severe patients, and this decrease correlated with thrombocytopenia.  Finally the higher CCR expression was accompanied by loss of functionality which could be due to a mechanism of desensitizing to compensate altered receptor expression.  The dysregulation of CCRs and their ligands observed during acute period suggest that chemokine pathway would participate in HUS development.