title: Macrophages promote cyst growth in polycystic kidney disease.
abstract: Polycystic kidney disease (PKD) exhibits an inflammatory component, but the contribution of inflammation to cyst progression is unknown. Macrophages promote the proliferation of tubular cells following ischemic injury, suggesting that they may have a role in cystogenesis. Furthermore, cultured Pkd1-deficient cells express the macrophage chemoattractants Mcp1 and Cxcl16 and stimulate macrophage migration. Here, in orthologous models of both PKD1 and PKD2, abnormally large numbers of alternatively activated macrophages surrounded the cysts. To determine whether pericystic macrophages contribute to the proliferation of cyst-lining cells, we depleted phagocytic cells from Pkd1(fl/fl);Pkhd1-Cre mice by treating with liposomal clodronate from postnatal day 10 until day 24. Compared with vehicle-treated controls, macrophage-depleted mice had a significantly lower cystic index, reduced proliferation of cyst-lining cells, better-preserved renal parenchyma, and improved renal function. In conclusion, these data suggest that macrophages home to cystic areas and contribute to cyst growth. Interruption of these homing and proliferative signals could have therapeutic potential for PKD.
authors.affiliation: Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. anil.karihaloo@yale.edu
authors.forename: Anil
authors.initials: A
authors.lastname: Karihaloo
authors.forename: Farrukh
authors.initials: F
authors.lastname: Koraishy
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Huen
authors.forename: Yashang
authors.initials: Y
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Merrick
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caplan
authors.forename: Stefan
authors.initials: S
authors.lastname: Somlo
authors.forename: Lloyd G
authors.initials: LG
authors.lastname: Cantley
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000378:metabolism; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016891:Polycystic Kidney, Autosomal Dominant / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; C494192:Ly-6C antigen, mouse