Effects of mycophenolic acid mofetil on acute rejection of kidney allografts in rats.
Mycophenolic acid mofetil (MMF) is an agent which has recently gained a lot of attention. In clinical trials MMF has reduced the rate of acute rejection episodes in human recipients of kidney allografts by inhibiting inosin-monophosphat-dehydrogenasis (IMPDH), an enzyme involved in the purin metabolism and related to the expression of adhesion molecules. The aim of the present study was to analyze the effects of MMF upon the expression of adhesion molecules in transplanted kidney allografts. LBNF1 kidneys were orthotopically transplanted into Lewis rats and either treated with MMF (20 mg/kg/day) or vehicle. Rats were harvested 3, 5 and 7 days following transplantation. Immunohistology was performed with various monoclonal antibodies. In general, MMF resulted in a better preservation of graft structure by 7 days. Cellular infiltration and tubular atrophy were less pronounced. At day 3, macrophages were diminished in MMF-treated animals to a high extent, while the number of T-cells was almost identical as compared to controls. In addition, the number of cells positive for MHC class II and LFA-1 was reduced in the MMF-treated animals. In conclusion, MMF resulted in a markedly reduced leukocyte infiltrate, presumably based on a reduced expression of lymphocytic adhesion molecules and an interaction with macrophages.
Heemann
U
U
Department of Nephrology, University Hospital Essen, Germany.
Azuma
H
H
Schmid
C
C
Philipp
T
T
Tilney
N
N
D000818:Animals; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D016030:Kidney Transplantation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007166:Immunosuppressive Agents; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid