Free radical-mediated tissue injury in acute lung allograft rejection and the effect of superoxide dismutase.
BACKGROUND
The role of monocytes and neutrophils is crucial during acute allograft rejection. They have the capacity to generate toxic reactive oxygen intermediates in response to specific agonists that may act as tissue destructive molecules. We examined the possibility of reactive intermediate-mediated tissue injury in acute lung allograft rejection, as well as the effect of superoxide dismutase.


METHODS
Allogenic (Brown Norway to F344) or syngenic (F344 to F344) rat left-lung transplantation was performed. Generation of reactive oxygen intermediates in peripheral blood was evaluated by the method of luminol-dependent chemiluminescence. Cell membrane phospholipid peroxidation in the graft was measured as malondialdehyde concentration. The third group of animals having allografts received bovine erythrocyte superoxide dismutase (5,000 U/kg intravenously every 12 hours after transplantation).


RESULTS
Relative chemiluminescence response in the allograft recipient to normal F344 was elevated on postoperative day 1 (257%), then decreased slightly on day 3 (156%) and was elevated again on day 7 (560%) as the process of rejection progressed. Allograft tissue malondialdehyde levels (248.37 +/- 112.35 nM/whole lung, n = 6; p < 0.05 by Student's t test) were higher than isograft levels (139.29 +/- 35.93 nM/whole lung, n = 6) on day 7. Superoxide dismutase treatment significantly ameliorated the histologic degree of rejection on day 7.


CONCLUSIONS
These results demonstrate the tissue destructive activity of reactive oxygen intermediates during lung allograft rejection. To scavenge free radicals may be a useful therapeutic modality in the management of acute lung allograft rejection.
Shiraishi
T
T
Second Department of Surgery, Fukuoka University School of Medicine, Japan.
Kuroiwa
A
A
Shirakusa
T
T
Kawahara
K
K
Yoneda
S
S
Kitano
K
K
Okabayashi
K
K
Iwasaki
A
A
D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000201:enzymology; D005500:Follow-Up Studies; D005609:Free Radicals / Q000009:adverse effects; D006084:Graft Rejection / Q000209:etiology* / Q000517:prevention & control; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D015227:Lipid Peroxidation; D008163:Luminescent Measurements; D008165:Luminol; D016040:Lung Transplantation / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008563:Membrane Lipids / Q000378:metabolism; D009000:Monocytes / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000502:physiology*; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000627:therapeutic use*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D000975:Antioxidants; D005609:Free Radicals; D007202:Indicators and Reagents; D008563:Membrane Lipids; D010743:Phospholipids; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D008165:Luminol; D013482:Superoxide Dismutase