[15, 16] In IRI and unilateral ureteric obstruction
(UUO), Ly6Chigh monocytes represent the major infiltrating cell subtype responsible for inducing CH5424802 datasheet injury.[13, 17] Macrophages can be further defined by their ‘activation’ pathway. Ly6Chigh macrophages express interleukin (IL)-1β and Cxcl2, which are associated with the classical (or M1) pathway of activation. In contrast, Ly6Clow macrophages share gene expression characteristics with the alternative activation (M2) pathway, which is associated with lower production of pro-inflammatory cytokines. In 1992, Zeier et al. reported that CD68-positive macrophages were present in the renal interstitium of ADPKD patients with both
early and advanced kidney failure. Scarce interstitial infiltrates (mean score 1.4, on a scale from 0 to 3) were found in ADPKD patients, however no interstitial infiltrate values were published for the control groups. More recently, Ibrahim observed BVD-523 clinical trial dense aggregates of interstitial CD68-positive macrophages in human ADPKD tissue, but did not report inflammatory cell staining for controls. Although there do not appear to be any studies demonstrating the presence of macrophages in human ARPKD, mononuclear infiltrates exist in other ciliopathies such as nephronophthisis, and in animal models resembling human ARPKD (discussed below). Several animal models of PKD display an accumulation of inflammatory cells in the renal interstitium (summarized in Table 2). These inflammatory cells occur in animals with ADPKD mutations (Pkd1 and Pkd2)
as well as non-orthologous ADPKD and ARPKD models, suggesting that they are a common manifestation of all types of cystic renal disease. In addition, Mrug et al. profiled renal gene expression in the cpk mouse, and found that several of the most over-expressed genes were associated with macrophages (e.g. Ccr2 and CD68) and the alternatively activated macrophage pathway (e.g. Ccl17).[37, 38] Likewise, a quarter of overexpressed genes in the Cy rat were related to macrophages.[37, 39] C57BL/6J-cpk (cpk/cpk) mouse Orthologous to human nephronophthisis 9; resembles human MycoClean Mycoplasma Removal Kit ARPKD. It is unclear whether inflammatory mononuclear cells instigate and promote cystic disease in PKD, or buffer the extent of renal injury. In addressing this, it is helpful to consider the time-course of macrophage accumulation. In the Lewis Polycystic Kidney (LPK) rat, cyst formation precedes the appearance of interstitial macrophages. Similarly in the DBA/2FG-pcy mouse, infiltrating cells do not appear until 18 weeks post-partum, although numerous cysts are established by week 8. Thus, infiltrating cells appear to be a response to, rather than a cause of cyst development in these models.