Circulating fibrocytes in ischemia-reperfusion injury and chronic renal allograft fibrosis.
BACKGROUND
Interstitial fibrosis in chronic allograft injury has been suggested as a major cause of the loss of allograft.


METHODS
To clarify the involvement of circulating fibrocytes (CF) and α-smooth muscle actin (SMA)-positive cells in renal allograft injury, we investigated 36 renal transplanted cases at 0 h, 1 h, 2-4 weeks, 4-8 weeks, and 1 year, and 5 normal controls. Double immunofluorescence analysis for both COL1 and CD45 indicating CF (/mm(2)), and the positive area (%) of α-SMA and Masson trichrome (MT) stain were detected by an image analyzing system.


RESULTS
The mean number of CF was 0 in controls and 4.0 in total transplanted specimens (p < 0.05). CF correlated with the α-SMA-positive area in the graft (R(2) = 0.39, p < 0.01), but not with Banff 2005 scores. The number of CF increased in 2-4 weeks; however, decreased 1 year after transplantation. α-SMA-positive area gradually increased at 1 year concomitant with the increase of MT-positive area. A similar phenomenon was observed in a case of primary nonfunction kidney from 0 h to 6 weeks after transplantation. The electron microscopy score of fibrosis around peritubular capillaries was correlated positively with COL1-positive area (R(2) = 0.72, p < 0.01), but negatively with infiltrated CF (R(2) = 0.25, p < 0.05).


CONCLUSIONS
CF were transiently induced, probably due to ischemia-reperfusion injury, but fibrosis only slightly progressed in this process. The α-SMA-positive myofibroblasts may accelerate the expansion of fibrosis around peritubular capillaries in chronic allograft injury.
Division of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Ishikawa, Japan.
Shogo
S
Kimura
Mitsuhiro
M
Asaka
Hirokatsu
H
Atsumi
Junko
J
Imura
Keiji
K
Fujimoto
Yoshihiro
Y
Chikazawa
Masaru
M
Nakagawa
Hiroshi
H
Okuyama
Hideki
H
Yamaya
Hitoshi
H
Yokoyama
D000199:Actins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002196:Capillaries / Q000473:pathology; D002452:Cell Count; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D006085:Graft Survival; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D016030:Kidney Transplantation / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D058628:Myofibroblasts / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications*; D018709:Statistics, Nonparametric; D013997:Time Factors
C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human