title: Graft morphology correlates with fibroblast activity in cardiac allograft rejection.
abstract: Several extracellular matrix substances, such as hyaluronan and fibronectin, may affect graft viability by their involvement in cell adhesion and in migration. These substances are produced locally in the tissue by fibroblasts. The aim of this study was to investigate the activation state of intragraft fibroblasts under various immunosuppressive treatments and to correlate these with morphological parameters. Syngeneic (n = 5) and allogeneic rat (n = 5-6/group) heterotopic heart transplantations were performed. Allogeneically transplanted animals were immunosuppressed with cyclosporine, mycophenolate mofetil or prednisolone. After 10 days, the transplanted hearts were removed for subsequent isolation of intragraft fibroblasts and for evaluation of graft morphology. The hyaluronan synthesis of graft fibroblasts correlated with the cellular infiltration (p < 0.05) and the interstitial oedema (p < 0.05) of the cardiac grafts. In general, proliferation rate and hyaluronan production were of the same magnitude in fibroblasts from allogeneic hearts under immunosuppression with cyclosporine, mycophenolate mofetil or prednisolone as in fibroblasts from syngeneic grafts. A pool of fibroblasts isolated from cardiac grafts of non-immunosuppressed, allogeneically transplanted rats (n = 4) showed considerably higher levels. We concluded that fibroblast activity correlates to the viability of the tissue rather than to the specific drug used for immunosuppression.
authors.forename: Tomas
authors.initials: T
authors.lastname: Lorant
authors.forename: Cecilia
authors.initials: C
authors.lastname: Emanuelsson
authors.affiliation: Department of Transplantation Surgery, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: M Y
authors.initials: MY
authors.lastname: Quach
authors.affiliation: Department of Transplantation Surgery, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tufveson
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016572:Cyclosporine / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D006084:Graft Rejection / Q000378:metabolism*; D016027:Heart Transplantation; D006820:Hyaluronic Acid / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology; D011239:Prednisolone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D006820:Hyaluronic Acid; D011239:Prednisolone; D009173:Mycophenolic Acid