Figure 8.

Function of VEGF-dependent regulation of IP-10 in allograft rejection. (a) Confluent cultures of murine myocardial endothelial cells were treated for 4 hours with recombinant murine VEGF or IFN-γ alone or VEGF in combination with IFN-γ as indicated. Total RNA was harvested from endothelial cells and the expression of IP-10 was analyzed by RNase protection assay. (b and c) The ability of VEGF to mediate IP-10-dependent trafficking and rejection was evaluated using anti-VEGF and anti–IP-10 in fully MHC-mismatched C57BL/6 (H-2^b) or IP-10^–/– (H-2^b) donor hearts transplanted into BALB/c (H-2^d) mice. Recipients of wild-type grafts were treated with anti-VEGF alone, or with anti-VEGF in combination with anti–IP-10. Recipients of IP-10^–/– donor grafts were treated with anti-VEGF. Both anti–IP-10 and anti-VEGF were administered according to the schedule outlined in Methods. As illustrated in b, we found that addition of anti-VEGF with anti–IP-10 significantly prolonged allograft survival in wild-type combinations (P < 0.005); and in c, anti-VEGF prolonged survival in mice that received IP-10^–/– donor hearts (P < 0.04). The survival of control untreated wild-type grafts are illustrated by the dotted line.