Temporary changes in macrophages and MHC class-II molecule-expressing cells in the tubulointerstitium in response to uranyl acetate-induced acute renal failure in rats.

The present study was designed to asses the dynamic changes in macrophages (Møs) with or without expression of major histocompatibility complex (MHC) class-II molecule in response to uranyl acetate-induced acute renal failure (ARF) in rats. ED1+ monocytes/Møs infiltrated into the interstitium as early as day 2, peaked in number on day 5 after uranyl acetate-induced ARF. ED1+ cells did not correlate with necrotic tubules but accumulated abundantly in the vicinity of the Ki67+ regenerating proximal tubules around days 4-5. Afterward, regeneration of proximal tubules was accelerated. After day 5, some ED1+ cells entered the tubular lumen, and became ED1+ giant cells, which had features of phagocytic Møs by immunoelectron microscopy, peaking in number on day 7. Most ED1+ cells did not incorporate [(3)H]-thymidine, indicating lack of active proliferation. The number of OX6+ cells (directed to MHC class-II molecule) in the interstitium significantly increased on day 4 and peaked on day 5. Double staining revealed that ED1+OX6- cells entered the tubular lumen while ED1+OX6+ cells remained in the peritubular regions. Osteopontin (OPN) protein and mRNA were significantly upregulated. No specific relationship could be found between OPN+ regenerating proximal tubules and ED1+ cells, but most ED1+ giant cells were OPN+ and intermingled among OPN+ cell debris. Our findings suggest that ED1+ Møs are actively associated with regenerating proximal tubules and, thus, might promote proximal tubular regeneration. ED1+OX6- Møs may function as scavengers and phagocytose cellular debris in the tubular lumen, cleaning the wound site. OPN might be involved in this process. ED1+OX6+ Møs in the peritubular regions may act as outpost of the defense system to monitor incoming antigens. Our data indicate that Møs with or without expressing MHC class-II molecule contribute to the defense and repair of injured proximal tubules in this ARF.