A Study of Allograft Kidney Rejection Occurring Simultaneously in Whole Organ and Ear Chamber Grafts in the Rabbit

Abstract

Most of the early studies on allograft rejection have been concerned with the morphological changes seen either in biopsy tissue or after removal of whole organs at different time intervals after grafting. Some have studied the organs in situ by indirect techniques which monitored physiological capacity or alterations in blood flow characteristicsVarious tissues have been studied microscopically by heterotopic implantation of organ fragments into such sites as brain (1), anterior chamber of the eye (2), renal capsule (3), hamster cheek pouch (4), and the transparent ear chamber of the rabbit (5). However, when these techniques were applied to allografted tissues, few were successful; and all those that did yield a clear microscopic view of the functioning tissues in vivo, such as hamster cheek pouch, the anterior chamber of the eye, or the rabbit ear chamber, exhibited atypical responses which were qtfite unlike the rejection that occurred when the same tissues were transferred as whole organs.When pieces of kidney were allografted into the rabbit ear chamber, they reestablished their blood circulation in 2-4 days by anastomosis of their cut vessels to the adjacent vasculature of the ear chamber membrane (6). Autografts appeared to function indefinitely, since autologous renal tissue was observed in the rabbit ear chamber withe ut change for 6 mo after fixation, and functioning myometrial autografts were observed for periods of up to 1 yr (6). Allografted renal tissues in the rabbit ear chamber reject after periods of up to 3 mo (6). A whole kidney allografted in similar rabbits is rejected in 7 days. When a whole kidney is allografted with an established ear chamber allograft from the same donor already in situ, both grafts reject synchronously over the following 7 days.This report describes the changes seen in the unmodified rejection of renal allografts occurring simultaneously in whole organs and minute implants within transparent ear chambers. Microscopic details of the process which results in whole organ renal allograft destruction can thus be studied in vivo by observation of the ear chamber grafts which are being rejected synchronously with the whole organ. Materials and MethodsRabbits.--Recipient rabbits were chosen from a closed colony of half-lop rabbits maintained at the Australian National University. Donor rabbits were unrelated; they were either from the same colony or sometimes from an entirely different strain from outside this colony.Grafting Procedures.-Ear chamber grafts: The procedure for transparent ear chamber insertion and the grafting of organ fragments into them was as previously described (6). The ear chamber grafts were taken from the donor's right kidney through a small flank incision. A wedge of cortex approximately 0.5 X 0.8 cm was transferred to the stage of a dissecting microscope, and the fragments for ear chamber implantation were prepaied from this by a second operator. A wedge of Gelfoam (Upjohn Co., Kalamazoo, Mich.) placed in the renal incision provided swift hemostasis, ...

Mechanisms of Mediator Release from Inflammatory Cells

“…Local formation of immune complexes in blood vessel walls (Arthus reaction) results in platelet accumulation, though their absolute requirement for the injury is controversial (Kravis and Henson, 1974). In vivo exocytosis from platelets has also been seen (Hobbs and Cliff, 1973).…”

“…In noncytotoxic release, the contents of the dense bodies are rapidly liberated-probably by discharge of the granule into the canalicular system (White and Estensen, 1972) or by exocytosis (Hobbs and Cliff, 1973). Preliminary evidence suggests that, as with mast cells, contact of the granule with cations from the extracellular fluid leads to dissolution of the granule and release of its contents (Uvnlis, 1971).…”

Alloantibody induced platelet responses in transplants: Potent mediators in small packages

“…Hobbs and Cliff [10] performed time-lapse cinematic microscopy of intravascular events in thin slices of allogeneic renal tissue that were implanted into observation chambers in rabbit ears. After these implants became revascularized, an orthotopic kidney was transplanted from the same donor, and the two transplants were found to reject simultaneously.…”

“…In transplants, platelets quickly engage leukocytes and increase leukocyte interactions with vascular endothelium [10]. Platelets interact with leukocytes through several mechanisms including release of chemokines, shedding of microparticles and direct cell contact.…”

Immunosuppression in rabbits: skin and kidney allografts

“…Few authors have reported observations on rejection processes in renal allografts in this species (Heron, 1971;Hobbs & Cliff, 1973), and there is even less information on attempts to modify rejection (Dunn & Randall, 1974).…”