Nitric oxide production in host-versus-graft and graft-versus-host reactions in the rat.
The present study was designed to determine whether .N = O produced in vivo during the rejection of histoincompatible tissues might permit serum NO2-/NO3- levels to serve as markers of a rejection reaction. Rat syngeneic and allogeneic liver, heart, bone marrow/spleen cell, small bowel, skin, and sponge matrix grafts were performed and the stable end-products of .N = O, NO2-/NO3-, were serially assayed in the serum of the grafted animals. A significant rise of serum NO2-/NO3- levels in the allografted animals preceded the onset of clinical signs of rejection or graft-versus-host disease, with the exception of the skin and sponge matrix graft models, where elevated serum NO2-/NO3- levels were never observed. In all transplant models, normal serum NO2-/NO3- levels were observed at all times in animals that received syngeneic grafts. Furthermore, treatment of allograft recipients with the immunosuppressive agents FK 506 or cyclosporine A inhibited .N = O production. Determination of serum creatinine levels demonstrated that the elevated serum NO2-/NO3- levels were not caused by kidney dysfunction. Serum NO2-/NO3- levels might be useful early serum markers of the initiation of a rejection reaction or graft-versus-host disease when functional markers of graft dysfunction are not apparent.
Langrehr
J M
JM
Department of Surgery, University of Pittsburgh, Pennsylvania 15261.
Murase
N
N
Markus
P M
PM
Cai
X
X
Neuhaus
P
P
Schraut
W
W
Simmons
R L
RL
Hoffman
R A
RA
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D006087:Graft vs Host Reaction; D016027:Heart Transplantation / Q000276:immunology; D006789:Host vs Graft Reaction; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007421:Intestine, Small / Q000276:immunology / Q000637:transplantation; D016031:Liver Transplantation / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors
D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D016572:Cyclosporine; D016559:Tacrolimus