Hyperacute renal allograft rejection in the rabbit. The role of platelet-activating factor and of cationic proteins derived from polymorphonuclear leukocytes and from platelets

The macroscopic signs of rejection, the levels of circulating transplantation antibodies, the histologic and immunocytochemical aspects, and the levels of platelet-activating factor (PAF) present in the venous blood were studied in two groups of rabbits that had received renal allografts, one group presensitized with multiple skin grafts and a second group unsensitized, as well as in a third group of rabbits that had received renal autografts. All of the eight allografts hyperacutely rejected by presensitized recipients had deposits of rabbit IgG, IgM, and C3 along the endothelia of the vessels and massive intravascular accumulation of platelets (Pt) as soon as 5 minutes after revascularization. PAF release was detected in 2 to 10 minutes after revascularization and was present throughout most of the 60 minutes of observation. Sixty minutes after transplantation Pt and polymorphonuclear leukocytes (PMN) obliterated the vasculature and deposits of Pt- and PMN-derived cationic proteins were detected in the lumina and in the walls of the capillaries. Similar, but less severe, findings were observed in three of six renal allografts which had transient episodes of rejection after transplantation into presensitized recipients. In contrast, circulating transplantation antibodies, macroscopic signs of rejection, vascular immune deposits, release of PAF, and microvascular thrombosis were not detected in renal allografts transplanted into unsensitized recipients or in renal autografts. The results indicate that in hyperacute renal allograft rejection there is an immediate fixation of transplantation antibodies and complement of the aggregation, and degranulation of Pt and PMN in the vasculature, resulting in a binding of Pt and PMN-derived cationic proteins to the walls of the capillaries. It is conceivable that PAF release and Pt and PMN cationic proteins may contribute, together with other lysosomal enzymes, vasoconstriction, and coagulation, to the pathogenesis of antibody- and complement-mediated hyperacute graft injury.