Effect of elimination of donor Kupffer cells and/or recipient macrophages on acute rejection in liver transplantation.
OBJECTIVE
Kupffer cells/macrophages have pivotal roles of antigen presentation and cytokine production in the acute rejection after liver transplantation. In this study, we attempted to eliminate donor Kupffer cells and/or recipient macrophages by administration of liposome encapsulated LE-Cl2MDP (dichloromethylene diphosphonate) for clarification of the effect of depletion of Kupffer cells and macrophages on acute rejection.


METHODS
To compare the survival, five groups were prepared: i) non-treatment group, ii) Kupffer cells eliminated group: transplanted Kupffer cells eliminated graft, iii) administration after liver transplantation group: injected LE-Cl2MDP twice after liver transplantation of non-treated graft, iv) additional administration group: transplanted Kupffer cells eliminated graft and injected LE-Cl2MDP twice after liver transplantation, and v) frequent administrations after liver transplantation group: injected LE-Cl2MDP every day for one week after liver transplantation of non-treated. Liver function tests, histological examination, histochemical staining of Kupffer cells and macrophages were carried out.


RESULTS
Survival days were not prolonged by Kupffer cells elimination of the graft or by depletion of migrated macrophages of recipient. In additional in the administration group, in which both Kupffer cells of the graft and migrated macrophages of recipient were eliminated, graft survival was prolonged significantly. But hyper bilirubinemia, hepatic fibrosis, and slight mononuclear cell infiltration were recognized.


CONCLUSIONS
These results suggested that both donor Kupffer cells and recipient macrophages play important roles in acute rejection in liver transplantation.
Akamatsu
Yorihiro
Y
Second Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.
Ohkohchi
Nobuhiro
N
Doi
Hideyuki
H
Satomi
Susumu
S
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000963:Antimetabolites / Q000494:pharmacology; D004002:Clodronic Acid / Q000494:pharmacology; D006084:Graft Rejection / Q000503:physiopathology*; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000502:physiology*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000276:immunology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains
D000963:Antimetabolites; D004002:Clodronic Acid