Induction of heat shock proteins in a rat composite tissue allotransplantation model of acute rejection.

Background: Clinical cases of composite tissue allotransplantation have been reported, but the exact mechanisms of allograft rejection remain unclear. The current study examined the possible involvement of heat shock proteins in major histocompatibility complex-compatible minor-mismatch composite tissue allotransplantation rejection. Methods: Allotransplantation (Fisher 344 to Lewis) and isotransplantation (Lewis to Lewis) of rat lower extremities were performed. Temporal profiles of 70-kDa and 60-kDa heat shock proteins (heat shock protein 70 and heat shock protein 60) were conducted by quantitative Western blot analysis and immunohistochemistry. Analyses were performed immediately after reperfusion (day 0) and on postoperative days 1, 3, 7, and 12 (n = 5 for quantitative Western blot analysis and n = 5 for immunohistochemistry). Results: The expression levels of the inducible forms of heat shock protein 70 and heat shock protein 60 were uniformly and significantly augmented until postoperative day 7 in the allografts, compared with the isografts (p < 0.001 for each protein). Immunoreactivities to heat shock protein 70 and heat shock protein 60 in keratinocytes, hair follicular cells, and endothelial cells of the subdermal vascular plexus were enhanced in the allografts early on postoperative day 1. Positive staining of hair follicles extended to deeper parts of the hair follicles and hair bulbs in the allografts on postoperative day 3. Although dendritic cells were positive for both heat shock protein 70 and heat shock protein 60, infiltrating lymphocytes were positive only for heat shock protein 60. Conclusions: These results suggest the possible involvement of heat shock proteins in the process of major histocompatibility complex-compatible minor-mismatch composite tissue allotransplantation rejection. Thus, modulation of the function of heat shock proteins might be an important therapeutic option for improving the outcome of minor-mismatch allografts.