Blocking of CD44-hyaluronic acid interaction prolongs rat allograft survival

Background. Lymphocyte activation and infiltration into a transplanted orga n is an integral component of the rejection process. Graft infiltration of lymphocytes requires adhesion of leukocytes to the endothelium, diapedesis, and transmigration. One of several proteins involved in this process is CD 44, which is known to interact with endothelial hyaluronan (HA). Blockade o f cell-matrix and cell-cell interactions have been used extensively for mod ulation of immune responses and graft rejection. Based on these observation s, we evaluated the effects of blocking CD44-HA interactions in a transplan tation model. Methods. We used a low molecular weight hyaluronic acid formulation (LMWHA) for the treatment of rat renal and cardiac allograft recipients. LMWHA was administered intraperitoneally at 0.5-5 mg/kg for 5-10 days after transpla ntation with or without a subtherapeutic dose of cyclosporine. Results. LMWHA monotherapy prolonged allograft survival significantly, but only for a few days, In combination with low-dose cyclosporine, long-term s urvival of allografts was observed in some of recipients. Conclusion. Further definition of the underlying mechanism of LMWHA therapy may provide a rationale for the development of novel, nontoxic, nonimmunog enic immunotherapies.