Surveillance of acute rejection in baboon renal transplantation by elevation of interferon-gamma inducible protein-10 and monokine induced by interferon-gamma in urine.
BACKGROUND
CXCR3 binding chemokines play a key role in recruitment of inflammatory cells into an organ transplant. This study addresses the question of whether urinary excretion of these chemokines correlates with acute rejection in a baboon kidney transplantation model.


METHODS
Seven outbred baboons underwent renal allotransplantation from major histocompatibility complex (MHC)-mismatched donors. The treatment of baboons consisted of anti-CD4 monoclonal antibody (mAb), anti-CD8 mAb, rapamycin, and mycophenolate mofetil (MMF). Urinary levels of interferon-gamma inducible protein-10 (IP-10) and monokine induced by interferon-gamma (Mig) were determined by ELISA. Renal biopsies were examined by immunohistochemical staining for CXCR3 and Mig.


RESULTS
Urinary levels of IP-10 and Mig increased significantly in all of the five baboons at the time of acute rejection of renal transplant. The IP-10 and Mig levels did not rise in two nonrejecting baboons. In two baboons, urinary levels of IP-10 and Mig rose before the elevation of the serum creatinine. In renal biopsies, expression of Mig was detected in glomeruli, tubules, and infiltrating cells, and the expression was significantly elevated in biopsies with acute rejection (P<0.01). CXCR3 was constitutively expressed in tubular cells in biopsies derived from both normal grafts and grafts with acute rejection. Whereas the infiltrating cells were increased in the biopsies with acute rejection, the expression of CXCR3 was also significantly higher (P<0.01) in these infiltrating cells compared with those in the normal controls.


CONCLUSIONS
This study shows an important correlation between urinary excretion of IP-10 and Mig and acute rejection in baboon kidney transplantation.
Division of Transplantation, Department of Surgery, Clinical Science Center, University of Wisconsin, Madison, WI 53792, USA.
Turan
T
Kanmaz
Ping
P
Feng
Jose
J
Torrealba
Jean
J
Kwun
John H
JH
Fechner
Jacqueline M
JM
Schultz
Yinchen
Y
Dong
Hyoung Tae
HT
Kim
Wasim
W
Dar
Majed M
MM
Hamawy
Stuart J
SJ
Knechtle
Huaizhong
H
Hu
D000208:Acute Disease; D000818:Animals; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000652:urine*; D006084:Graft Rejection; D007371:Interferon-gamma / Q000494:pharmacology; D007668:Kidney / Q000737:chemistry; D016030:Kidney Transplantation; D010215:Papio; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma