Progression of kidney disease: blocking leukocyte recruitment with chemokine receptor CCR1 antagonists.
Chronic kidney disease (CKD) is usually associated with interstitial leukocytic cell infiltrates, which may contribute to disease progression by production of proinflammatory, proapoptotic, and profibrotic mediators. Recruiting leukocytes into the kidney involves local expression of chemotactic cytokines, that is, chemokines, that interact with respective chemokine receptors on the leukocyte's outer surface. Thus, specific chemokine receptor antagonists may represent an attractive therapeutic concept to interfere with renal leukocyte recruitment. Among the proinflammatory chemokine receptors, chemokine receptor (CCR)-1 has nonredundant roles for leukocyte adhesion to activated vascular endothelium and for transendothelial migration. In fact, blocking CCR-1 with specific small-molecule antagonists was shown to retard progression in various types of rodent CKD models. Here we discuss the perspective of CCR-1 as a new potential target for the treatment of CKD.
Anders
H-J
HJ
Nephrological Center, Medical Policlinic, Ludwig Maximilians-University Munich, Munich, Germany. hjanders@med.uni-muenchen.de
Ninichuk
V
V
Schlöndorff
D
D
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D024141:Collagen Type IV / Q000502:physiology; D018450:Disease Progression; D004317:Doxorubicin / Q000633:toxicity; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D016030:Kidney Transplantation; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000502:physiology; D014184:Transplantation, Homologous
C515300:CCR1 protein, human; D024141:Collagen Type IV; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D004317:Doxorubicin