The effects of suppressed expression of metabotropic glutamate receptor 5 (mGluR5) and accelerated expression of Fas ligand (FasL) mRNA on bone marrow (BM)/liver grafts in rat

The important roles of host liver metabotropic glutamate receptor 5 (mGluR5) and Fas ligand (FasL) genes in bone marrow (BM)/liver graft survival were shown using rat models. The bad effects of BM co-graft and granulocyte-macrophage colony-stimulating factor (GM-CSF) on liver graft survival were also assessed. Thirty-one Lewis rat livers were grafted a piece of Lewis or dark agouti (DA) BM alone or together with a section of liver, 9 of these were injected with GM-CSF. At 4-5 months post-transplantation, mGluR5 mRNA of host livers was measured quantitatively by reverse transcriptase (RT)-polymerase chain reaction (PCR). Eighteen experimental and 5 control rats were measured for FasL mRNA of the host liver. CD2^sup +^CD90^sup -^ cellular density was measured by flow cytometer (FCM) in all rats. Eight of 31 grafted and 3 of 7 control host livers showed absence or 50% reduction of mGluR5 mRNA with normal mGluR5 DNA (29%). Among 7 females grafted with Lewis male BM alone, 5 host livers showed low amounts of mGluR5 mRNA with signs of early graft acceptance. Among 8 males grafted with Lewis BM/livers and 7 females grafted with DA BM/livers, 2 males and 1 female had low levels of liver mGluR5 mRNA, in which the shrinking liver graft showed characteristically only a partial fusion to the host liver. Two male livers with better graft survival and 2 control male livers showed large amounts of the FasL gene products. In the 2 males with the activated FasL mRNA, the liver grafts were examined with an electron microscope. The liver grafted onto a host with no mGluR5 showed apoptotic changes such as massively developed rough endoplasmic reticulum and small mitochondria with a normal nucleus. The graft on the liver with activated mGluR5 had almost normal structures. Nine experiment rats injected with GM-CSF, which resulted in liver and spleen dendritic cell proliferation, showed aggravated graft rejection. FCM results of the females grafted BM alone showed a similar suppression of spleen CD2^sup +^CD90^sup -^ cells to those of the males injected with GM-CSF.[PUBLICATION ABSTRACT]