Angiogenesis in the huPBL-SCID model of human transplant rejection

Background. Angiogenesis is characteristic of chronic inflammatory reaction s. The process of angiogenesis is reported to be proinflammatory in part du e to enhanced adhesion events and in part due to increased perfusion and pe rmeability to sites of inflammation. However, little is known about the ass ociation between angiogenesis and rejection. Methods. Severe combined immune deficient mice are permissive for the growt h of human skin allografts and human peripheral blood mononuclear cells (PB MC). Human PBMC were injected into mice by intravenous or intraperitoneal i njection. The infiltration of cells and the associated angiogenesis reactio ns in the skin allografts were analyzed temporally by videomicroscopy and s patially by immunohistochemistry. Results. Human alloreactive mononuclear cells migrated to human skin but no t mouse skin within hours after the intravenous infusion of PBMC. Within 3 days, areas of angiogenesis were observed in the skin grafts at the sites o f infiltrates. The vessel densities in skin grafts were 24+/-6 vessels per calibrated grid at baseline on the day of the infusion and increased to 55/-16 vessels per calibrated field by day 10. Skin grafts harvested from hum anized severe combined immune deficient mice 7-14 days after the intraperit oneal infusion of human PBMC showed a similar increased density of vessels that were spatially associated with mononuclear cell infiltrates. Conclusions. A significant angiogenesis response was associated with the ce ll infiltrates in the human skin allografts. The onset uf angiogenesis appe ared after the initial development of localized infiltrates and preceded th e development of microvascular destruction. These findings suggest that all oreactive T cells and/or monocytes mediate the angiogenesis response in ski n allografts.