Antibody binding to endothelial and epithelial antigens triggers pig-to-rabbit xenograft rejection and its absence results in atypical complement deposition.
In pig-to-rabbit kidney xenograft (PRKX), endothelial antigen determinants (EAD) are immediately recognized by IgG and IgA, while IgM does not react with them. The purpose of this study was to investigate the different roles of IgG, IgA, IgM, and complement in the hyperacute rejection of a PRKX model. Nine isolated Landrace pig kidneys were each perfused with 10 ml normal New Zealand rabbit serum. Perfusates (serum A) were collected after discarding the first 0.5 ml. Serum A and rabbit complement were then incubated for 30 min with frozen sections of normal pig kidney. After washing with buffer solution all the specimens were treated for immunohistochemistry. Three frozen sections of normal Landrace pig kidney and three samples of normal New Zealand rabbit serum were used as controls. Immunohistochemical analysis of the nine perfused kidneys demonstrated IgG, IgA and C3 deposition on the peritubular and glomerular vascular endothelium. No IgM reactivity was shown. In the frozen sections exposed to serum A, immunofluorescence showed minimal IgG, IgA and C3 reactivity while IgM deposition was clearly evident on the tubular epithelium. Immunofluorescence of frozen sections exposed to rabbit complement, done by fluorescein-labeled goat anti-rabbit C3 antibodies were positive only in the glomerular endothelium. The same rabbit complement was active in antibody dependent cytotoxicity on human T cells. Our results indicated that in the PRKX model, IgG and IgA acted as preformed antibodies recognizing endothelial EAD. IgM did not bind to any endothelial molecules, but recognized antigens located on the brush border of the tubular epithelium. Furthermore, in this model, absence of antigen-antibody complexes resulted in atypical complement deposition.
Marino
I R
IR
Transplantation Institute, Department of Surgery, University Health Center of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Celli
S
S
Ferla
G
G
Doyle
H R
HR
Maggiano
N
N
Zetti
G
G
Musiani
P
P
D000818:Animals; D003165:Complement System Proteins / Q000032:analysis*; D005260:Female; D006084:Graft Rejection / Q000473:pathology*; D007150:Immunohistochemistry; D016030:Kidney Transplantation / Q000276:immunology* / Q000379:methods / Q000473:pathology; D011817:Rabbits; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000379:methods / Q000473:pathology
D003165:Complement System Proteins