Document Detail

Induction of transforming growth factor-beta during cardiac allograft rejection.
MedLine Citation:
PMID:  8335896     Owner:  NLM     Status:  MEDLINE    
The polypeptides of the transforming growth factor-beta (TGF-beta) family are potent endogenous immuno-regulators. Using a rat cardiac allograft transplant model, we investigated the expression of the precursor forms of TGF-beta 1, TGF-beta 2, and TGF-beta 3 and the latent TGF-beta binding protein (LTBP) by immunohistochemistry. The activity of TGF-beta in the extracts from transplanted as well as normal hearts was measured using a bioassay, and Northern blot analysis was performed on RNA extracts. The transplanted hearts were analyzed both during acute rejection up to 6 days and during chronic rejection up to 6 mo after transplantation and compared with normal controls. The animals of the chronic rejection group received cyclosporin A for immunosuppression. The TGF-beta bioactivity dramatically increased in the transplanted allografts during the chronic rejection process compared to the normal hearts, and so did the immunostaining as well as the mRNA levels for TGF-beta 1 and, to a lesser extent, the immunostaining for TGF-beta 2. TGF-beta 3 expression remained unchanged and was only found in the myocardium in trace amounts. During the acute rejection process up to 6 days after transplantation, TGF-beta immunoreactivity increased only slightly, whereas the TGF-beta mRNA was severalfold increased. Control animals treated with cyclosporin A showed a similar pattern at day 6 with regard to TGF-beta expression. LTBP was induced simultaneously with TGF-beta 1 and occurred within interstitial spaces of the myocardium. The TGF-beta was produced by macrophage-like infiltrating lymphocytes. In conclusion, highly elevated levels of TGF-beta and LTBP were found during chronic rejection of cardiac allografts in rats. The induction of TGF-beta may counteract the rejection process and could be useful for new therapeutic approaches in the prevention of allograft rejection.
J Waltenberger; A Wanders; B Fellström; K Miyazono; C H Heldin; K Funa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  151     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1993 Jul 
Date Detail:
Created Date:  1993-08-25     Completed Date:  1993-08-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1147-57     Citation Subset:  AIM; IM    
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
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MeSH Terms
Blotting, Northern
Carrier Proteins / analysis
Graft Rejection*
Heart Transplantation / adverse effects*
Intracellular Signaling Peptides and Proteins*
Latent TGF-beta Binding Proteins
Myocardium / metabolism
RNA, Messenger / analysis
Rats, Inbred WKY
Transforming Growth Factor beta / biosynthesis*,  genetics
Transplantation, Homologous
Reg. No./Substance:
0/Carrier Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Latent TGF-beta Binding Proteins; 0/RNA, Messenger; 0/Transforming Growth Factor beta

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