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The effect of anticomplementary cobra venom factor on hyperacute rat cardiac allograft rejection
Abstract:
Cobra venom factor was used as a probe to evaluate the effect of depression of recipient hemolytic C3 activity on the sequential morphologic features of hyperacute cardiac allograft rejection in the rat. A series of ACI cardiac allografts transplanted to Lewis recipients presensitized &with ACI skin grafts was studied at arbitrary time periods over the initial 24 hours posttransplantation. The usual morphologic features of hyperacute rejection in this model, platelet aggregation, intravascular fibrin, endothelial destruction, neutrophil infiltration, and myocardial necrosis, were not observed in all allografts when recipient hemolytic C3 activity was virtually undetectable at the time of transplantation. Furthermore, allograft binding of rat C3 was not detected by immunofluorescence, although staining for IgG was commonly encountered. Despite profound depression of recipient hemolytic C3 activity, however, mononuclear cells were observed within the allograft microcirculation by 2 hours posttransplantation, and changes consistent with early cellular rejection were present in allografts examined at 24 hours. This study provides evidence that complement activation by graft-bound alloantibody is a critical effector mechanism of hyperacute rejection in this inbred rat model.
Insights
Depressing complement component 3 (C3) activity in recipients prevented hyperacute rejection in rat cardiac allografts. However, early cellular rejection still occurred, indicating complement activation by alloantibody is key to hyperacute rejection.
Area of Science:
- Immunology
- Transplantation Biology
- Pathology
Background:
- Hyperacute rejection is a rapid form of organ transplant rejection.
- Complement activation is implicated in hyperacute rejection.
- The specific role of complement component 3 (C3) in this process requires further elucidation.
Purpose of the Study:
- To investigate the effect of depressed recipient hemolytic C3 activity on hyperacute cardiac allograft rejection in rats.
- To determine the sequential morphologic features of rejection when C3 activity is inhibited.
- To assess the role of complement activation in mediating hyperacute rejection.
Main Methods:
- Cobra venom factor was used to depress recipient hemolytic C3 activity.
- ACI cardiac allografts were transplanted into Lewis rats presensitized with ACI skin grafts.
- Allografts were examined morphologically at various time points within 24 hours post-transplantation.
Main Results:
- Depression of recipient hemolytic C3 activity prevented typical hyperacute rejection features like platelet aggregation, fibrin deposition, and necrosis.
- No C3 deposition was detected in allografts, though IgG staining was common.
- Mononuclear cell infiltration and early cellular rejection changes were observed despite C3 depression.
Conclusions:
- Complement activation by graft-bound alloantibody is a critical effector mechanism in hyperacute cardiac allograft rejection in this rat model.
- While complement is crucial for hyperacute rejection, cellular rejection mechanisms can still initiate rejection even with C3 inhibition.