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.
Fujigaki
Yoshihide
Y
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, 431-3192 Hamamatsu, Japan. yf0516@hama-med.ac.jp
Sun
Di Fei
DF
Goto
Tetsuo
T
Hishida
Akira
A
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016253:Microscopy, Immunoelectron; D009942:Organometallic Compounds / Q000633:toxicity; D053495:Osteopontin; D010587:Phagocytosis / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D016482:Urinalysis
D015415:Biomarkers; D000949:Histocompatibility Antigens Class II; D009942:Organometallic Compounds; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; C005460:uranyl acetate