Naturally acquired anti-alpha Gal antibodies in a murine allograft model similar to delayed xenograft rejection.
Antibodies directed against galactose-alpha1,3-galactose (alphaGal) are believed to play an important role in the pathogenesis of delayed xenograft rejection (DXR). This study was designed to determine whether alpha1,3-galactosyltransferase-deficient (Gal KO) mice can naturally acquire a sufficient anti-alphaGal titre to cause the delayed type rejection of alphaGal-expressing hearts. Gal KO mice of various ages were assessed for anti-alphaGal antibody levels. alphaGal-expressing hearts were transplanted heterotopically into these mice and monitored daily. Rejecting and surviving hearts were evaluated histologically. In Gal KO mice greater than 6-month-old, 64% had an anti-alphaGal antibody titre above the background level. When wild-type alphaGal-expressing hearts were transplanted into this group, 45% of grafts rejected within 5 to 13 days. Histological examination of the rejected hearts displayed marked tissue damage and an inflammatory infiltrate of predominantly macrophage/monocytes. Surviving grafts showed preserved morphology. Like humans, Gal KO mice naturally develop anti-alphaGal antibodies with age. The titre in these mice was sufficient to cause a "delayed-type" rejection of a significant proportion of alphaGal-expressing cardiac grafts. This model thus provides an opportunity to investigate the role of naturally acquired anti-alphaGal antibodies in the pathogenesis of DXR.
Salvaris
E
E
Immunology Research Center, St Vincent's Hospital, Fitzroy, Australia.
Gock
H
H
Han
W
W
Murray-Segal
L
L
Barlow
H
H
Mottram
P
P
Pearse
M
M
Cowan
P
P
Goodman
D
D
d'Apice
A J
AJ
D000818:Animals; D004187:Disaccharides / Q000235:genetics / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007518:Isoantibodies / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous / Q000276:immunology* / Q000473:pathology
D004187:Disaccharides; D007518:Isoantibodies; C055075:galactosyl-(1-3)galactose