TU Bing,LIANG Shao-yong,CHEN Yong,LONG Fei-wu,PENG Yong,LIU Zuo-jin,XU Ming-qing,YAN Lu-nan,GONG Jian-ping.Expression of Fas ligand protein in Kupffer cells and its role in inducing T cells apoptosis in rat liver graft[J].J Amry Med Univ (J Third Mil Med Univ),2008,30(14):1322-1326.
TU Bing,LIANG Shao-yong,CHEN Yong,LONG Fei-wu,PENG Yong,LIU Zuo-jin,XU Ming-qing,YAN Lu-nan,GONG Jian-ping.Expression of Fas ligand protein in Kupffer cells and its role in inducing T cells apoptosis in rat liver graft[J].J Amry Med Univ (J Third Mil Med Univ),2008,30(14):1322-1326.DOI:
Expression of Fas ligand protein in Kupffer cells and its role in inducing T cells apoptosis in rat liver graft
Objective To detect the expressions of Fas/FasL in Kupffer cells(KCs)and graft-infiltrating T lymphocytes (TLCs)
and explore the role of KCs in induced-T cells apoptosis through Fas/FasL pathway. Methods Totally 112 male SD rats were randomized into 4 groups
that is
live transplantation group (28 donors and 28
recipients)
and GdCl
3
pretreatment group (28 donors and 28 recipients). The donors of pretreatment group received intravenous injection of GdCl
3
at 10 mg/kg
and the donors of the other group was injected with the same volume of normal saline. Then liver transplantation was carried out with the modified two-step perfusion method. The recipients were killed immediately or 48 h after the operation. Isolated KCs and TLCs were counted and TLCs were classified using flow cytometry (FCM). Expression of FasL protein in KCs and TLCs was evaluated with immunocytochemical staining and laser scanning confocal microscopy (LSCM). mRNA and protein expression of Fas and FasL in KCs and TLCs were detected with RT-PCR and Western blot. The cytotoxicity of KCs against TLCs via Fas/FasL system and the effect of anti-FasL antibody in this process was assessed using
3
H thymidine release assays. Results Compared with the liver transplantation group
the counts of isolated KCs in GdCl
3
group were lower while the number of TLCs and CD8
+
T cell were significantly increased (P0.05)
and less FasL-positive KCs and more Fas-positive TLCs were detected (P0.05). Expression of FasL mRNA and its protein in KCs was decreased (P0.05)
but expression of Fas mRNA and its protein in TLCs had no significant difference. An 18-hour
3
H thymidine release assay showed that in 48 h after transplantation
KCs isolated from the liver transplantation group induced more TLCs than those from GdCl
3
group. The KCs-mediated killing of TLCs was significantly inhibited by treatment of anti-fasL antibody. Conclusion KCs-mediated TLCs killing induces liver transplantation tolerance via the Fas/FasL pathway. GdCl
3
suppresses expression of FasL in KCs and blocks the induction of liver graft tolerance.
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