Ramos Maria Victoria, Ruggieri Matias, Panek Analia Cecilia, Mejias Maria Pilar, Fernandez-Brando Romina Jimena, Abrey-Recalde Maria Jimena, Exeni Andrea, Barilari Catalina, Exeni Ramon, Palermo Marina Sandra
*Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental Medicine (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires, Argentina.
†Departamento de Nefrología, Hospital Municipal del Niño, San Justo, Provincia de Buenos Aires, Argentina.
Clin Sci (Lond). 2015 Aug;129(3):235-44. doi: 10.1042/CS20150016.
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.
溶血尿毒综合征（HUS）是产志贺毒素（Stx）的大肠杆菌胃肠道感染的主要并发症。单核细胞通过产生使内皮细胞对Stx作用敏感并迁移至受损肾脏的细胞因子，促进HUS的发展。由于CC趋化因子受体（CCR）参与单核细胞向受损组织的募集，我们分析了这些受体在HUS发病机制中的作用。我们以健康儿童作为对照，分析了急性期HUS患者外周血单核细胞中CCR1、CCR2和CCR5的表达。我们观察到HUS患者单核细胞中每个细胞的CCR表达增加，同时CCR1+、CCR2+和CCR5+单核细胞的绝对数量也增加。有趣的是，前瞻性分析证实CCR1表达与HUS严重程度呈正相关。血浆趋化因子水平评估显示，严重HUS患者血浆中正常T细胞表达和分泌的调节激活正常T细胞表达和分泌的趋化因子（RANTES）蛋白减少，且这种减少与血小板减少相关。最后，较高的CCR表达伴随着功能丧失，这可能是由于一种脱敏机制来补偿受体表达的改变。CCR表达增加与HUS严重程度相关，表明这些受体的失调可能导致肾损伤风险增加。活化的单核细胞可被趋化因子募集，然后受体可能失调。急性期观察到的CCR及其配体的失调表明趋化因子途径参与了HUS的发展。
