Sequential immunological targeting of chronic experimental arterial allograft.
Arterial wall is the main site involved in the chronic rejection process. The rat aortic allograft model was used here to characterize and describe the sequential evolution of the different targets and effectors of arterial wall immunological injury and response during arterial allograft rejection. Rat abdominal aortae were isografted or allografted from Brown-Norway to Lewis rats. Endothelial and smooth muscle cell injury and humoral and cellular immunological effectors were characterized from 0 to 60 days after transplantation using a battery of specific antibodies. The intimal proliferative response was also characterized over this time. Isografted Brown-Norway aorta adventitia had very few cellular components, which suggests that donor adventitia would be poorly antigenic in allografts. In contrast, allograft adventitia was the site of a major inflammatory cell invasion in which the expression of an adhesion molecule by colonizing capillary endothelial cells could play a main role. This adventitial infiltration continued as long as medial smooth muscle persisted. The luminal endothelial cells disappeared early, probably associated with macrophage margination. In contrast, medial smooth muscle cell disappearance occurred later and was specifically targeted by immunoglobulins. Intimal proliferation was the most delayed phenomenon, involving both inflammatory cell infiltration at an early stage and later myofibroblastic proliferation, and could be related to the specific expression of growth factors in this layer. The rat aortic allograft model appeared useful for characterizing specific targets and effectors of chronic arterial graft rejection, demonstrating an early stage of endothelial injury and the presence of immunoglobulins involved in chronic medial smooth muscle cell injury.
Plissonnier
D
D
Unit 367 INSERM, Paris, France.
Nochy
D
D
Poncet
P
P
Mandet
C
C
Hinglais
N
N
Bariety
J
J
Michel
J B
JB
D000818:Animals; D001011:Aorta / Q000473:pathology / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000473:pathology; D006084:Graft Rejection / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G