HYPERACUTE RENAL-ALLOGRAFT REJECTION IN THE RABBIT - THE ROLE OF PLATELET-ACTIVATING FACTOR AND OF CATIONIC PROTEINS DERIVED FROM POLYMORPHONUCLEAR LEUKOCYTES AND FROM PLATELETS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 51  (2) , 148-161
Abstract
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 2 groups of rabbits that had received renal allografts, 1 group presensitized with multiple skin grafts and a 2nd group unsensitized, as well as in a 3rd group of rabbits that had received renal autografts. All of the 8 allografts hyperacutely rejected by presensitized recipients had deposits of rabbit IgG, IgM and [complement component] C3 along the endothelia of the vessels and massive intravascular accumulation of platelets (Pt) as soon as 5 min after revascularization. PAF release was detected in 2-10 min after revascularization and was present throughout most of the 60 min of observation. After 60 min 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 6 renal allografts which had transient episodes of rejection after transplantation into presensitized recipients. 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. Apparently, in hyperacute renal allograft rejection there is an immediate fixation of transplantation antibodies and complement of the recipient to endothelial antigens of the graft, local release of PAF, and massive accumulation, 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. 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.