Regulation of fibroblasts by activated and non-activated immune cells.
BACKGROUND
Rejection of transplanted tissue is characterized by cell infiltration and interstitial edema. Graft fibroblasts and fibroblast products are partly involved in the regulation of both these phenomena. Knowledge about the mechanisms behind fibroblast activation may lead to new strategies to prevent rejection. This study investigated whether cells of the immune system have the capacity to regulate fibroblast activation.


METHODS
Fibroblasts isolated from rejecting heart transplants or from normal heart tissue were cultured in the presence of supernatants of stimulated or non-stimulated immune cells. The immune cells were challenged either in vitro (incubation with phytohemagglutinin) or in vivo (organ transplantation). Fibroblast proliferation and hyaluronan production were measured.


RESULTS
Normal, sub-confluent heart fibroblasts showed an increased proliferation rate in the presence of supernatants of activated immunocompetent cells, irrespective of if these cells had been stimulated in vitro or in vivo. As expected, proliferation rate and hyaluronan production were upregulated in fibroblasts isolated from rejecting tissue. However, supernatants of biopsy specimens obtained from non-rejecting organs (syngeneic transplants or normal hearts) had an inhibitory effect on the growth rate of confluent fibroblasts isolated from rejecting tissue.


CONCLUSIONS
We conclude that graft-infiltrating cells and immune cells activated in vitro have the capacity to stimulate fibroblasts, most probably as a result of the production and secretion of fibroblast-stimulating factors.
Johnsson
Cecilia
C
Department of Transplantation Surgery, University Hospital, Uppsala, Sweden. Cecilia.Johnsson@surgsci.uu.se
Lorant
Tomas
T
Tufveson
Gunnar
G
D000818:Animals; D049109:Cell Proliferation; D004487:Edema; D005347:Fibroblasts / Q000502:physiology*; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006820:Hyaluronic Acid / Q000096:biosynthesis; D007111:Immunity, Cellular; D008297:Male; D010835:Phytohemagglutinins / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology; D016042:Transplantation, Heterotopic
D010835:Phytohemagglutinins; D006820:Hyaluronic Acid