Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Involvement of fractalkine pathway in the pathogenesis of childhood hemolytic uremic syndrome

Abstract

Thrombotic microangiopathy and acute renal failure are cardinal features of post-diarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cells damage induced by Shiga toxin (Stx), through the interaction with its globotriaosyl ceramide receptor. However, inflammatory processes contribute to the pathogenesis of HUS by sensitizing cells to Stx. Fractalkine (FKN), a CX3C transmembrane chemokine expressed on epithelial and endothelial cells upon activation, is involved in the selective migration and adhesion of specific leukocytes subsets to tissues. Here, we demonstrated a selective depletion of circulating mononuclear leukocytes expressing the receptor for FKN (CX3CR1) in HUS patients. We found a unique phenotype in children with HUS, distinct from that seen in healthy, uremic or infected controls, in which monocytes lost CX3CR1, down-modulated CD62L and increased CD16. In addition, CD56dim natural killer (NK) subpopulation was decreased leading to an altered peripheral ratio of CD56dim:CD56bright from 10.0 to 4.5. Noteworthy, we found a negative correlation between the percentage of circulating CX3CR1+ leukocytes and the severity of renal failure. Finally, CX3CR1+ leukocytes were observed in renal biopsies from HUS patients. We suggest that the interaction of CX3CR1+ cells with FKN present on activated endothelial cells may contribute to renal injury in HUS.