Liver sinusoidal endothelial cell function in rejected and spontaneously accepted rat liver allografts.
Studies have suggested that liver sinusoidal endothelial cells (LSEC) may play an important role in tolerance induction. In this study, we evaluated the functional difference of LSEC in rejection and spontaneous acceptance of liver allografts by using rat liver transplant model. LSEC function was determined by circulating hyaluronic acid (HA) levels and fluorescein isothiocyanate-labeled formaldehyde-treated serum albumin (FITC-FSA) uptake. Additional parameters include the number of circulating lymphocytes and LSEC apoptosis. In spontaneously accepted group, we found (i) significantly lower serum HA levels (P = 0.002), (ii) a more rapid uptake of FITC-FSA, and (iii) a reduced number of circulating CD8a+ cells when compared with the rejection group. Strikingly, HA levels in spontaneously accepted group are even lower than syngeneic control group. Further investigation revealed that interleukin-1beta, a cytokine that promotes LSEC function, was higher in DA than in Lewis rats. In summary, our study demonstrates that LSEC function is better preserved in spontaneously accepted rat liver allografts than in those which are rejected. These findings warrant further studies to verify if LSEC actively contributes to liver transplant outcome or just a target of different immunologic responses.
Ge
Xupeng
X
Division of Transplantation Surgery, Karolinska University Hospital-Huddinge, Karolinska Institute, Stockholm, Sweden. xge@partners.org
Nowak
Grzegorz
G
Ericzon
Bo-Göran
BG
Sumitran-Holgersson
Suchitra
S
D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004705:Endocytosis / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology*; D006820:Hyaluronic Acid / Q000097:blood; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000473:pathology*; D016031:Liver Transplantation / Q000473:pathology*; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl; D011917:Rats, Inbred Lew; D012709:Serum Albumin / Q000493:pharmacokinetics; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014184:Transplantation, Homologous
D016827:CD8 Antigens; D016207:Cytokines; C518288:FITC-albumin; D012709:Serum Albumin; D006820:Hyaluronic Acid; D016650:Fluorescein-5-isothiocyanate