Nitric oxide production in host-versus-graft and graft-versus-host reactions in the rat.

Abstract

The present study was designed to determine whether *N 0 produced in vivo during the rejection of histoincompatible tissues might permit serum NOQ/N0 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 endproducts of N 0, NOQ/N0, were serially assayed in the serum of the grafted animals. A significant rise of serum NOQ/NO-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 NO /NO-levels were never observed. In all transplant models, normal serum NO /NO-levels were observed at all times in animals that received syngeneic grafts. Furthermore, treatment ofallograft recipients with the immunosuppressive agents FK 506 or cyclosporine A inhibited N 0 production. Determination of serum creatinine levels demonstrated that the elevated serum NO /NO-levels were not caused by kidney dysfunction. Serum NOQ/NO-levels might be useful early serum markers of the initiation of a rejection reaction or graft-versushost disease when functional markers of graft dysfunction are not apparent. (J. Clin. Invest. 1992. 90:679-683.)

Pathophysiology of acute graft-versus-host disease: recent advances

“…NO also inhibits the repair mechanisms of target tissue destruction by inhibiting proliferation of epithelial stem cells in the gut and skin (263). In humans and rats, the development of GVHD is preceded by an increase in serum levels of NO oxidation products (264)(265)(266)(267).…”

Role of nitric oxide following cardiac transplantation

“…33 Nitrate and nitrite are the end products of nitric oxide breakdown in the blood and are an index of nitric oxide production. 34,35 Two rat cardiac allograft studies have shown increased plasma nitrate and nitrite during the early stages of rejection. 18,36 Urinary nitrate excretion has also been shown to increase eight-fold in untreated rejection compared to that seen in isografts.…”

Increased urinary nitrate excretion associated with hepatic allograft rejection in experimental rat models and clinical cases

“…Plasma nitrite levels and urinary nitrate excretion have been used as an index of NO production in vivo [14]. Langrehr et al have demonstrated that plasma nitrate levels increased in host-versus-graft and graft-versus-host responses in rats [13]. Wjnlaw et al have documented increased urinary nitrate excretion in cardiac allograft rejection in an experimental study [21].…”