Heme-oxygenase-1 expression correlates with severity of acute cellular rejection in lung transplantation.
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.


METHODS
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.
Bonnell
Mark R
MR
Department of Surgery, University of Florida, Gainesville 32610-0286, USA.
Visner
Gary A
GA
Zander
Dani S
DS
Mandalapu
Subbarao
S
Kazemfar
Kristy
K
Spears
Linnea
L
Beaver
Thomas M
TM
D000818:Animals; D006084:Graft Rejection / Q000201:enzymology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D006801:Humans; D007150:Immunohistochemistry; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins; D018384:Oxidative Stress; D009195:Peroxidase / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology
D008565:Membrane Proteins; D009195:Peroxidase; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1