Prevention of chronic renal allograft rejection by SERP-1 protein.
BACKGROUND
In previous studies we have demonstrated that Serp-1, a myxoma virus encoded serine protease inhibitor, dramatically inhibits neointimal hyperplasia in vascular injury and aortic transplant models. Here we examined the effect of peritransplant Serp-1 administration on chronic renal allograft rejection.


METHODS
Rat renal transplants were performed with sequential recipient sacrifice on postoperative days 2, 10 and 140 to examine both the acute and chronic effects of Serp-1 in recipient rats.


RESULTS
Serp-1 administration reduced early posttransplant injury (POD 2) with less acute tubular and vascular necrosis. This translated into a reduction of the characteristic late stage changes of chronic rejection (POD 140), with significantly decreased glomerulosclerosis and neointimal hyperplasia. Effects of Serp-1 treatment were already evident as early as POD 2 with markedly decreased levels of TGF-beta mRNA witnessed at both the early and late time points (POD 2, 10 and 140).


CONCLUSIONS
We have demonstrated that peritransplant Serp-1 viral protein decreased early injury and allowed reduced chronic rejection in a rat renal model. Recipients treated with Serp-1 are associated with a decrease in TGF-beta mRNA levels in the allografts suggesting that the serine protease inhibitor may inhibit TGF-beta transcription and its profibrotic effects.
Multiorgan Transplant Program, London Health Sciences Centre, University Campus, 339 Windermere Road, London, Ontario N6A 5A5, Canada.
Eric L R
EL
Bédard
Jifu
J
Jiang
Jacqueline
J
Arp
Hua
H
Qian
Hao
H
Wang
Haiyan
H
Guan
Liying
L
Liu
Neil
N
Parry
Peter
P
Kim
Bertha
B
Garcia
Xing
X
Li
Colin
C
Macaulay
Grant
G
McFadden
Alexandra
A
Lucas
Robert
R
Zhong
D000818:Animals; D002908:Chronic Disease; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control*; D016030:Kidney Transplantation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D015843:Serpins / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014184:Transplantation, Homologous; D014764:Viral Proteins / Q000627:therapeutic use*
D012333:RNA, Messenger; D015843:Serpins; D016212:Transforming Growth Factor beta; D014764:Viral Proteins