Linked Life Data

12819868

Source:http://linkedlifedata.com/resource/pubmed/id/12819868

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-6-23
pubmed:abstractText
Further development in organ transplantation requires the utilization of new immunosuppressive drugs that-in addition to being effective against rejection-do not block tolerance. We previously reported that FTY 720, a drug that alters lymphocyte trafficking, has marked anti-rejection properties. We now investigate how FTY 720 influences tolerance in a model of graft acceptance by donor-specific blood transfusion (DSBT). Two different transplant models--heart transplantation (Htx) and intestinal transplantation (Itx)--were studied. We performed orthotopic Itx and heterotopic Htx using fully mismatched inbred male RA (RT1(p)) and PVG (RT1(c)) rats as donors and recipients. Tolerance was induced by DSBT on pre-transplant day -12. To test the effect of FTY 720 on DSBT-induced tolerance, we administered FTY 720 orally prior to DSBT. Itx: control rats succumbed to rejection at 18+/-4 days. DSBT alone prolonged survival to 101.9+/-18 days (P<0.05 vs untreated). Long-term survivors were tolerant (acceptance of secondary donor-specific Htx). Adjunction of FTY 720 prior to DSBT reduced survival to 55.9+/-44.7 days (P<0.05). However, long-term survivors still accepted secondary donor-specific Htx. Htx: control rats survived 9+/-0.6 days. DSBT alone prolonged survival indefinitely (>120 days) and induced tolerance (acceptance of secondary donor-specific Htx). Unlike in Itx, adjunction of FTY 720 prior to DSBT did not reduce Htx survival. Acceptance of secondary donor-specific Htx was not influenced by FTY 720. In Itx, FTY 720 counteracts the beneficial effect of pre-transplant DSBT and triggers acute rejection of primary, but not secondary grafts. In Htx, however, FTY 720 allows full development of tolerance. The mechanisms by which FTY 720 causes rejection in primary intestinal but not in heart grafts need to be elucidated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0934-0874
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
383-90
pubmed:dateRevised
2008-6-5
pubmed:meshHeading
pubmed-meshheading:12819868-Animals, pubmed-meshheading:12819868-Antibodies, Anti-Idiotypic, pubmed-meshheading:12819868-Antibody Formation, pubmed-meshheading:12819868-Blood Transfusion, pubmed-meshheading:12819868-Heart Transplantation, pubmed-meshheading:12819868-Histocompatibility, pubmed-meshheading:12819868-Immunoglobulin G, pubmed-meshheading:12819868-Immunoglobulin M, pubmed-meshheading:12819868-Immunosuppressive Agents, pubmed-meshheading:12819868-Intestines, pubmed-meshheading:12819868-Lymphocyte Culture Test, Mixed, pubmed-meshheading:12819868-Lymphocyte Subsets, pubmed-meshheading:12819868-Lymphocytes, pubmed-meshheading:12819868-Male, pubmed-meshheading:12819868-Propylene Glycols, pubmed-meshheading:12819868-Rats, pubmed-meshheading:12819868-Rats, Inbred Strains, pubmed-meshheading:12819868-Sphingosine, pubmed-meshheading:12819868-Tissue Donors, pubmed-meshheading:12819868-Transplantation, Heterotopic, pubmed-meshheading:12819868-Transplantation, Homologous, pubmed-meshheading:12819868-Transplantation Conditioning, pubmed-meshheading:12819868-Transplantation Tolerance
pubmed:year
2003
pubmed:articleTitle
The effect of FTY 720 on engraftment in a model of spontaneous allograft acceptance.
pubmed:affiliation
Abdominal Transplant Department, University Hospital of Leuven, Herestraat 49, 3000 Leuven, Belgium.
pubmed:publicationType
Journal Article