Chemokine receptor CCR1: a new target for progressive kidney disease.
Infiltrating leukocytes are thought to contribute to the progression of kidney disease. Locally produced chemokines guide circulating leukocytes into the kidney, which renders therapeutic blockade of respective chemokine receptors on the leukocyte surface as potential targets for the inhibition of renal leukocyte recruitment. By using mutant mice and specific antagonists, we found that chemokine receptor CCR1 has non-redundant functions for leukocyte adhesion to activated vascular endothelium and for transendothelial diapedesis. Most importantly, CCR1 blockade with a specific small molecule antagonist can improve injury in several types of progressive kidney disease models, even if treatment is initiated in advanced disease states. Identification of new targets may add to the therapeutic options in chronic kidney disease.
Ninichuk
Volha
V
Nephrological Center, Medical Policlinic, Ludwig Maximilians University of Munich, Germany.
Anders
Hans-Joachim
HJ
D000818:Animals; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000276:immunology; D007674:Kidney Diseases / Q000276:immunology*; D010671:Phenylurea Compounds / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000276:immunology*; D012076:Renal Agents / Q000494:pharmacology
C515300:CCR1 protein, human; C515302:Ccr1 protein, rat; D010671:Phenylurea Compounds; D010880:Piperidines; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D012076:Renal Agents; C411885:BX 471