Induction of heat shock protein in cardiac allograft rejection - A cyclosporine-suppressible response

Elizabeth A. Davis, Bernadette H. Wang, Carole A. Stagg, William M. Baldwin, William A. Baumgartner, Fred Sanfilippo, Robert Udelsman

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The cellular response to a wide variety of stresses results in the synthesis of a family of proteins termed heat shock proteins (HSPs). To determine if acute allograft rejection could induce these proteins in a transplanted graft, we examined the HSP response to acute cardiac allograft rejection and analyzed the effect of immunosuppression upon this response. Donor hearts obtained from either Lewis (LEW) or ACI rats were heterotopically transplanted in recipient LEW rats. There were 4 experimental groups: untreated isografted (LEW to LEW) animals (n=14), untreated allografted (ACI to LEW) animals (n=14), cyclosporine-treated (10 mg/kg SQ/day) isografted animals (n=12), and cyclosporine-treated allografted animals (n=12). Animals were sacrificed on posttransplantation day 2, 4, or 6 (time of rejection for untreated allografts); n=4-5 for each time point per group. At these times tissue obtained from the transplanted heart was examined histologically and analyzed for HSP72 by quantitative Northern and Western blots. The level of HSP72 in the untreated allografts progressively increased between 2, 4, and 6 days posttransplantation and was significantly greater than that of the untreated isografts at all time points. The HSP72 response in cyclosporine-treated allografts was significantly reduced at 4 and 6 days posttransplantation compared with the untreated allografts. In contrast, there was no difference in the HSP response in treated versus untreated isografts. Additionally, there was no difference in HSP levels in cyclosporine-treated isografts and allografts. These findings demonstrate that HSP expression in the transplanted heart correlates directly with the evolution of acute allograft rejection, and that immunosuppressive therapy inhibits the HSP response. These studies also raise the possibility of a functional role for HSPs in the allogeneic immune response.

Original languageEnglish (US)
Pages (from-to)279-284
Number of pages6
Issue number2
StatePublished - Jan 27 1996

ASJC Scopus subject areas

  • Transplantation


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