Selective chemokine and receptor gene expressions in allografts that develop transplant vasculopathy.
BACKGROUND
Chemokine systems probably play a role in transplant vasculopathy; however, a comprehensive study of the expression of chemokines and their receptors in this disease has not been performed.


METHODS
The expression of all the rat chemokines and chemokine receptor genes for which the nucleotide sequences are known were quantitatively monitored using the fluorescence-based real-time reverse-transcriptase polymerase chain reaction technique, and selected cytokine-receptor pairs were determined using immunohistochemical staining. The analysis covered the whole time course of transplant vasculopathy in 2 different graft models (cardiac and aortic grafts) with 4 different strain combinations of rats.


RESULTS
Among the 13 receptor genes examined, the CXCR3, CCR5, and CCR2 genes and those of their corresponding ligands were selectively and strongly induced in grafts that develop transplant vasculopathy. The expression patterns of the receptors were similar in both cardiac and aortic allografts, although their induction and their absolute levels of expression were amplified several fold in the grafted aorta compared with heart grafts. The genes were induced before morphologic changes became apparent and expression was sustained during the whole period of neointimal formation. Interestingly, immunohistochemical staining for CXCR3 showed a unique pattern of expression: we found weak expression on cells in the outer layer of the neointima and adventitia and found the strongest staining in the innermost layer of the neointima.


CONCLUSIONS
This study suggested diagnostic as well as potential functional roles of the chemokine-receptor pairs IP10-CXCR3, RANTES-CCR5, and MCP1-CCR2 in rat models of transplant vasculopathy.
Horiguchi
Kei
K
Department of Surgery, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Japan.
Kitagawa-Sakakida
Satoru
S
Sawa
Yoshiki
Y
Li
Zhan-zhuo
ZZ
Fukushima
Norihide
N
Shirakura
Ryota
R
Matsuda
Hikaru
H
D000818:Animals; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D016027:Heart Transplantation / Q000276:immunology*; D007150:Immunohistochemistry; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D014158:Transcription, Genetic
C515336:Ccr2 protein, rat; D018925:Chemokines; C515189:Cxcr3 protein, rat; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine