Transplant approach establishes that kidneys are responsible for serum CSF-1 but require a stimulus in MRL-lpr mice.
Colony stimulating factor-1 (CSF-1) is a chemoattractant and growth factor for macrophages. In autoimmune MRL-lpr mice, CSF-1 is detected in the circulation and there is an increase in CSF-1 transcripts and macrophages in the kidney. The purpose of this study was to establish whether the MRL-lpr kidney is responsible for increasing serum CSF-1, and to determine if the expression of CSF-1 requires a circulating component in MRL-lpr mice. We transplanted a MRL-lpr kidney with nephritis [serum CSF-1 = 32.6 +/- 5.1 colony forming units (CFU)] into a bilaterally nephrectomized normal MRL-++ recipient. Circulating CSF-1 increased from 1.2 +/- CFU to 14.1 +/_ 5.6 CFU in recipients by one week. Continuous production of CSF-1 required a stimulating component since: (1) CSF-1 in the kidney and circulation disappeared several weeks after engraftment into MRL-++ mice and (2) isolated glomeruli from MRL-lpr required stimulation to express CSF-1. In the transplanted MRL-lpr kidney, hypercellularity in the glomerulus and interstitium (predominantly macrophages) returned to normal as rapidly as two weeks after engraftment into MRL-++. Thus, this study establishes that the kidney is responsible for circulating CSF-1 in MRL-lpr mice. Without the autoimmune environment CSF-1, macrophages, but not T cells, disappear and nephritis resolves.
Naito
T
T
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Griffiths
R C
RC
Coffman
T M
TM
Kelley
V R
VR
D000818:Animals; D046508:Culture Techniques; D005260:Female; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D009392:Nephrectomy; D009393:Nephritis / Q000097:blood* / Q000473:pathology / Q000601:surgery
D008070:Lipopolysaccharides; D016173:Macrophage Colony-Stimulating Factor