INFECTION-ASSOCIATED MACROPHAGE ACTIVATION ACCELERATES CHRONIC RENAL ALLOGRAFT REJECTION IN RATS1
作者:
Nagano2 Hiroaki,
Nadeau2,3 Kari,
Kusaka2 Mamoru,
Heeman4 Uwe,
Tilney2,5 Nicholas,
期刊:
Transplantation
(OVID Available online 1997)
卷期:
Volume 64,
issue 11
页码: 1602-1605
ISSN:0041-1337
年代: 1997
出版商: OVID
数据来源: OVID
摘要:
Background.The influence of infection-associated cellular activation on chronic rejection of kidney grafts was assessed in an established rat model by administration of lipopolysaccharide (LPS), an endotoxin and a potent stimulator of various cell populations including mononuclear cells and renal epithelial cells.Methods.Lewis recipients of F344 kidneys were treated with low-dose cyclosporine (1.5 mg/kg/day × 10 days). Animals with well-functioning grafts received a single dose of LPS (2 mg in 1 ml of NaCl, intraperitoneally) at 4 or 8 weeks after engraftment. Untreated control rats, which later experienced chronic rejection, were given 1 ml of NaCl.Results.Administration of LPS during the early quiescent phase of chronic rejection accelerated the chronic process, functionally (proteinuria), morphologically, immunohistologically, and by reverse-transcriptase polymerase chain reaction as compared with untreated controls. Infiltration of macrophages and their associated factors was especially affected.Conclusions.As the later events of chronic rejection seem to be mediated primarily by macrophages and their products, administration of LPS accelerated the tempo and activity of these cells in the development of chronic rejection. These findings may explain the clinical observation that infection may be an important risk factor for chronic allograft rejection.
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