Cell and extracellular matrix rejection in arterial concordant and discordant xenografts in the rat.
Vascularized xenografts are rejected acutely and hyperacutely in concordant or discordant combinations, respectively. We investigated the impact of the donor-recipient combination on the rejection of arterial xenografts, analyzing the cellular and extracellular matricial compartments. Aortic xenografts were performed in a concordant (hamster) and a discordant (guinea pig) combination with Lewis rat. Graft cells and immune effectors were characterized by immunohistochemistry after 15 min and up to 30 days postimplantation. Macroscopic and microscopic structure of the grafts was studied at 60 days. IgC in the concordant combination and C3, C5b9, and IgM in the discordant combination deposited on endothelial cells, acutely and hyperacutely, respectively. The same immune effectors deposited on medial smooth muscle cells, but later than on endothelial cells. In both combinations the medial extracellular matrix was covered by IgM and IgC and infiltrated by monocytes (90%) and T lymphocytes (10%), with elastinolysis in the vicinity of monocytes. However, elastin resorption in the media at day 60 differed in concordant and discordant xenografts(75+/-10% and 99+/-1%, respectively). Intimal thickening and aneurysm developed in concordant and discordant combinations, respectively. Unlike arterial allografts, arterial xenografts are not a homogeneous group. The donor-recipient combination determines the mechanism and the timing of graft cell rejection, as well as the magnitude of medial elastin injury. As a consequence, chronic graft remodeling differs in the two combinations.
Allaire
E
E
Unit 367 INSERM and Unit 430, Paris, France.
Mandet
C
C
Bruneval
P
P
Bensenane
S
S
Becquemin
J P
JP
Michel
J B
JB
D000208:Acute Disease; D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology*; D001012:Aorta, Abdominal / Q000637:transplantation*; D001013:Aorta, Thoracic / Q000637:transplantation*; D003176:Complement C3 / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis*; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000276:immunology*; D005109:Extracellular Matrix / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012377:Rodentia / Q000276:immunology*; D013045:Species Specificity; D014183:Transplantation, Heterologous / Q000276:immunology*
D000910:Antibodies, Heterophile; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D007074:Immunoglobulin G; D007075:Immunoglobulin M