Infection-associated macrophage activation accelerates chronic renal allograft rejection in rats.
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 x 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.
Nagano
H
H
Harvard Medical School, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Nadeau
K C
KC
Kusaka
M
M
Heeman
U W
UW
Tilney
N L
NL
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology*; D007239:Infections / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D008070:Lipopolysaccharides