Increased immunoreactivity of transforming growth factor-beta in human kidney transplants.
Transforming growth factor-beta (TGF-beta) has been known to be involved in the pathogenesis of various kidney diseases. TGF-beta is also a potent immunosuppressor that has been shown to be induced after allogeneic transplantation. We have studied the distribution of immunoreactive TGF-beta proteins in different compartments of 21 allogeneic transplanted kidneys that had been rejected through acute (eight interstitial or six vascular) and chronic (seven vascular) processes. This distribution was compared with that in seven non-rejected transplanted and five non-transplanted kidneys with intact morphology. There were no obvious differences between the three groups of rejected grafts and the transplanted non-rejected group for the expression of TGF-beta s. A major difference was seen between transplanted kidneys, which exhibited clearly positive TGF-beta and LTBP1 (latent TGF-beta binding protein) immunoreactivities, and the non-transplanted kidneys. The non-transplanted kidneys showed only very weak or no immunoreactivity for these proteins. The morphologically intact non-rejected grafts showed a significantly increased immunoreactivity compared with the non-transplanted kidneys. When the transplanted kidneys were classified into two groups (i.e. with or without diabetes mellitus) and compared with regard to the expression of all TGF-beta s, no difference was found. Thus, transplantation was the most important predictor for expression of TGF-beta s and LTBP1, and the largest expression increase in the allografts occurred in the interstitium, followed by the glomeruli and blood vessels. Tubuli and lymphocyte aggregates stained only faintly. The results imply that TGF-beta is induced rapidly after kidney transplantation. This induction can suppress immunoreactivation, but concomitantly promotes changes such as arteriosclerosis and fibrosis associated with rejection.
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
I
I
Lantz
E
E
Dimény
E
E
Larsson
B
B
Fellström
K
K
Funa
D006801:Humans; D007678:Kidney Glomerulus / Q000737:chemistry; D016030:Kidney Transplantation / Q000276:immunology*; D007684:Kidney Tubules / Q000737:chemistry; D012077:Renal Artery / Q000737:chemistry; D012082:Renal Veins / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000276:immunology*
D016212:Transforming Growth Factor beta