Complement membrane attack complex and protectin (CD59) in liver allografts during acute rejection.
OBJECTIVE
The complement system is important in the rejection of xenografts, but very little is known about its activation in the rejection of allografts. Complement lysis is induced by the membrane attack complex (MAC), an aggregate of C5b, C6, C7, C8 and C9 molecules. The main defender against MAC is the CD59 molecule, also called protectin. In this study, the aim was to analyze the possible deposition of MAC and the fate of CD59 on distinct cell populations during liver allograft rejection.


METHODS
Liver allografts were monitored by frequent fine-needle aspiration biopsies (FNAB) to demonstrate the immunoactivation of rejection. To examine MAC and CD59 in the FNAB, in relation to the activation markers of rejection, IL2-receptor, MHC class II and ICAM-1 expression, specific monoclonal antibodies and immunoperoxidase staining were used.


RESULTS
Ten out of 21 consecutive liver transplants underwent a histologically confirmed episode of reversible acute rejection. In the FNAB, a significant increase of the activation markers IL2-receptor, class II and ICAM-1 correlated with the peak of inflammation during the episode. In association with inflammation, a significant deposition of MAC was recorded in neutrophils and lymphocytes infiltrating the graft and in the parenchymal cells. MAC deposition subsided together with the inflammation. A significant decrease in CD59 expression was seen in neutrophils during rejection, but CD59 expression on other inflammatory cells and hepatic tissue cells varied greatly.


CONCLUSIONS
Complement activation was seen in association with acute rejection of liver allografts and it led to MAC assembly on leukocytes and tissue cells. A decrease in CD59 expression was less clear-cut, but it may predispose the cells to complement-mediated elimination.
Lautenschlager
I
I
Fourth Department of Surgery, Helsinki University Central Hospital and University of Helsinki, Finland.
Höckerstedt
K
K
Meri
S
S
D000208:Acute Disease; D001707:Biopsy, Needle; D018957:CD59 Antigens / Q000276:immunology*; D015938:Complement Membrane Attack Complex; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016031:Liver Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous
D018957:CD59 Antigens; D015938:Complement Membrane Attack Complex; D000949:Histocompatibility Antigens Class II