Donor dopamine pretreatment inhibits tubulitis in renal allografts subjected to prolonged cold preservation.
BACKGROUND
In the present study, we used the Brown-Norway (BN) to Lewis model as a model for acute rejection, to test the hypothesis that dopamine (DA) treatment of BN donors significantly reduces the inflammatory response after renal transplantation.


METHODS
BN and Lewis rats (isograft controls) were treated for 24 hr with DA (5 microg/kg/min) or NaCl (0.9%), respectively. After 24 hr of cold storage in University of Wisconsin (UW) solution, renal allografts were orthotopically transplanted into Lewis recipients. All recipients received immunosuppression until they were sacrificed. Allografts were harvested one, three, five, and 10 days after transplantation and analyzed by light microscopy, immunohistochemistry (CD3, major histocompatibility complex [MHC] class II, ED1, P-selectin and intercellular adhesion molecule [ICAM]-1) and by RNase protection assay for cytokine mRNA.


RESULTS
Ten days after transplantation Banff tubulitis scores were significantly lower in DA-treated than in NaCl-treated allografts. No significant differences were found in Banff interstitial infiltration scores. The numbers of MHC class II+ and CD3+ cells were significantly decreased in DA-treated animals as assessed by immunohistochemistry. No differences were found in the number of ED1+, P-selectin+, and ICAM-1+ cells. The expression of Ltalpha, tumor necrosis factor, interleukin-1beta, and interleukin-2 mRNA was significantly reduced in DA-treated animals.


CONCLUSIONS
Our data indicate that donor DA treatment significantly inhibits tubulitis in renal allografts subjected to prolonged cold preservation. A reduced number of infiltrating MHC class II+ and CD3+ cells together with decreased cytokine expression could diminish renal scarring, reduce allograft immunogenicity, and hence improve transplantation outcome.
Liu
Zhenzi
Z
Fifth Medical Clinic, Klinikum Mannheim, University of Heidelberg, Heidelberg, Germany.
Hoeger
Simone
S
Schnuelle
Peter
P
Feng
Yuxi
Y
Goettmann
Uwe
U
Waldherr
Ruediger
R
van der Woude
Fokko J
FJ
Yard
Benito
B
D000818:Animals; D015925:Cryopreservation / Q000379:methods*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000008:administration & dosage*; D005921:Glomerulonephritis / Q000517:prevention & control*; D006084:Graft Rejection / Q000517:prevention & control*; D007150:Immunohistochemistry; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008853:Microscopy; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014019:Tissue Donors; D014184:Transplantation, Homologous
D016207:Cytokines; D012333:RNA, Messenger; D004298:Dopamine