This proposal is designed to examine the role of adhesion molecules in the intense cellular rejection seen when hyperacute rejection (HAR) is delayed in discordant xenograft models. Organs transplanted between discordant species undergo a rapid severe rejection over a matter of minutes which appears to be mediated by Compliment (C). When this HAR is delayed, by C depleting agents, the result is cellular infiltration and rejection which appears to be temporally different from allograft rejection. We propose to examine the cellular interactions between recipient leukocytes and the donor endothelium. More specifically, the role adhesion molecules play in cell recruitment and infiltration of the graft. We will examine the expression of cytokines in an attempt to shed light on the role they play. The ultimate goal is to allow for xenograft success between swine and humans to over come the donor shortage. That result is several years away but, we feel that the next barrier to xenograft transplantation is the cellular rejection seen when HAR is delayed Cellular interactions, specifically the adhesion molecule interaction between donor endothelial cells and recipient leukocyte, are central to this process. An understanding of these interactions is critical to overcoming this problem and may lead to therapeutic agents (monoclonal Ab) allowing xenografts to become a clinical reality.
| Johnson, E M; Leventhal, J; Dalmasso, A P et al. (1996) Inactivation of C3 and C5 prolongs cardiac xenograft survival and decreases leukocyte infiltration in a model of delayed xenograft rejection. Transplant Proc 28:603 |
| Johnson, E; Leventhal, J; Dalmasso, A et al. (1996) Use of a novel CD11b/CD18 inhibitory agent in a C6-deficient rat to evaluate delayed xenograft rejection. Transplant Proc 28:728 |
