Circulating fibrocytes in ischemia-reperfusion injury and chronic renal allograft fibrosis

Nephron Clin Pract. 2012;121(1-2):c16-24. doi: 10.1159/000341374. Epub 2012 Oct 16.

Abstract

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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Adult
  • Aged
  • Capillaries / pathology
  • Cell Count
  • Collagen Type I / metabolism
  • Female
  • Fibroblasts* / metabolism
  • Fibrosis
  • Graft Survival
  • Humans
  • Kidney / blood supply
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Transplantation / pathology*
  • Leukocyte Common Antigens / metabolism
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Myofibroblasts / metabolism
  • Reperfusion Injury / complications*
  • Statistics, Nonparametric
  • Time Factors

Substances

  • ACTA2 protein, human
  • Actins
  • Collagen Type I
  • Leukocyte Common Antigens
  • PTPRC protein, human