The atypical chemokine receptor 2 limits progressive fibrosis after acute ischemic kidney injury.

The atypical chemokine receptor 2 limits progressive fibrosis after acute ischemic kidney injury. Am J Pathol. 2018 Nov 15;: Authors: Lux M, Blaut A, Eltrich N, Bideak A, Müller MB, Hoppe JM, Gröne HJ, Locati M, Vielhauer V Abstract Following renal ischemia-reperfusion injury (IRI) resolution of inflammation allows tubular regeneration, whereas ongoing inflammatory injury mediated by infiltrating leukocytes leads to nephron loss and renal fibrosis, typical hallmarks of chronic kidney disease. The atypical chemokine receptor 2 (ACKR2) is a chemokine decoy receptor, that binds and scavenges inflammatory CC-chemokines and reduces local leukocyte accumulation. We hypothesized that ACKR2 limits leukocyte infiltration, inflammation, and fibrotic tissue remodeling after renal IRI, thus preventing progression to chronic kidney disease. Compared to wild-type, Ackr2 deficiency increased CC chemokine ligand 2 levels in tumor necrosis factor-stimulated tubulointerstitial tissue in vitro. In Ackr2-deficient mice with early IRI one or five days after transient renal pedicle clamping tubular injury was similar to wild-type, although accumulation of mononuclear phagocytes increased in postischemic Ackr2-/- kidneys. Regarding long-term outcomes, Ackr2-/- kidneys displayed more tubular injury five weeks after IRI, which was associated with persistently increased renal infiltrates of mononuclear phagocytes, T cells, Ly6Chigh inflammatory macrophages,...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research