Heme-oxygenase-1 expression correlates with severity of acute cellular rejection in lung transplantation - 24/08/11
, Gary A Visner, DO †, Dani S Zander, MD ‡, Subbarao Mandalapu, MD , Kristy Kazemfar, BS †, Linnea Spears, BS †, Thomas M Beaver, MD , ⁎ : FACS Department of Surgery, University of Florida, Gainesville FL, USA Abstract |
Background |
Heme-oxygenase-1 (HO-1) has been shown to play an important role in oxidative stress, and recent studies indicate that it is a graft survival protein in cardiac and liver transplant models. Our laboratory previously found HO-1 to be increased in human lung allografts with acute cellular rejection (ACR) and in active obliterative bronchiolitis. To better understand the role of HO-1 in ACR we studied the relationship between HO-1 expression and ACR in a rodent model of lung transplantation.
Study design |
Orthotopic left lung transplantation was performed from Lewis (donor) to Sprague-Dawley (recipient) rats, and ACR (Grade A0 to A4) was evaluated at days 3, 5, and 7. HO-1 expression was assessed by immunohistochemistry and Western analysis, and compared with the degree of ACR. Myeloperoxidase staining was evaluated as an indirect measure of oxidant stress. Donors and recipients were also treated with either an inhibitor of HO activity, tin protoporphyrin or an inducer, cobalt protoporphyrin, and the severity of ACR was compared with that in untreated allografts.
Results |
HO-1 expression was elevated in transplanted versus native lungs or isografts, and the degree of elevation was closely correlated with ACR grade (p < 0.001). Similarly, myeloperoxidase expression increased with time and severity of ACR. Administration of the metalloporphyrins, tin protoporphyrin and cobalt protoporphyrin, produced no significant difference in the degree of ACR, but did alter the severity of ischemia-reperfusion injury.
Conclusions |
Similar to what occurs in human lung transplantation, HO-1 expression is increased in a rodent lung transplant model of ACR and correlates with the severity of rejection. Altering its expression does not appear to affect the degree of ACR.
Le texte complet de cet article est disponible en PDF.Abbreviations : ACR, CoPP, HO-1, MPO, SnPP
Plan
 | Supported in part from the American Lung Association of Florida and the Department of Health, FL. |
Vol 198 - N° 6
P. 945-952 - juin 2004 Retour au numéro
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