The graft content of hyaluronan is increased during xenograft rejection

Abstract

Hyaluronan, a macromolecule with strong water binding capacity, is associated with interstitial oedema during rejection of allogeneic transplants. However, the involvement of hyaluronan during xenograft rejection has previously not been investigated. The aims of this study were to characterize hyaluronan content and distribution during rejection of concordant mouse-to-rat cardiac xenografts, and to explore the effects of hyaluronidase (HAse) on xenograft survival. Graft recipients were treated with 15-deoxyspergualin (DSG) or both HAse and DSG. Grafts were removed on day 5 from some of the animals to analyse hyaluronan and water content, while other animals were used to investigate graft survival. The hyaluronan content was measured by a radiometric assay and the distribution was analysed by histochemical staining. In xenografts undergoing rejection (the DSG group) there was a strong increase of the hyaluronan [555 +/- 93 microg/g dry weight (dw)] and water (82.7 +/- 0.4%) contents compared with normal mouse heart tissue (166 +/- 10 microg/g dw; P < 0.01 and 78.6 +/- 0.5%; P < 0.001, respectively). The combined use of HAse and DSG reduced the accumulation of hyaluronan (284 +/- 43 microg/g dw; P < 0.05 vs. DSG) but did not affect the average water content. The average graft survival time did not differ between the groups; however, three grafts in the HAse + DSG-treatment group survived much longer than the longest-surviving grafts in the DSG group. These data suggest that the graft content of hyaluronan considerably increases during xenograft rejection. HAse effectively reduces this accumulation, but does not affect the average water content.