Linked Life Data

9519734

Source:http://linkedlifedata.com/resource/pubmed/id/9519734

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-4-7
pubmed:abstractText
Early impairment of islet function and graft loss limit the success of allogeneic islet transplantation. Nonspecific inflammatory events occurring at the transplant site immediately after grafting, involving the production of cytokines and free radicals and sinusoidal endothelial cell (SEC) activation, may contribute to islet cell damage. To evaluate whether Kupffer cell inactivation would result in prolonged allograft survival in a model system of intrahepatic islet transplantation in rats, we systemically administered either gadolinium chloride (GdCl3) or dichloromethylene diphosphonate (Cl2MDP) to assess the effects of macrophage inactivation on rejection and on the release of proinflammatory molecules, as well as to assess the functional profile of SEC. The results obtained were compared with those observed in untreated, sham-injected animals and in rats receiving intraportal infusions of microbeads. Transient macrophage inhibition, particularly in hepatic Kupffer cells, is associated with significant prolongation of graft survival after intraportal islet allotransplantation (ITx) in rats: 7.2 days in the control group versus 11.9 days in the GdCl3 group (P < 0.01) and 15.6 days in the Cl2MDP group (P < 0.0006), respectively. Although systemic release of inflammatory mediators was observed only when islet transplantations were performed and it could be inhibited by macrophage-targeting treatments, perturbation of the functional profile of endothelial cells was also observed when microembolization was induced by the use of microbeads and could not be prevented by macrophage inhibition. These experiments provide evidence to support the concept that macrophages play a key role in early inflammatory events known to adversely affect islet engraftment and suggest that manipulation of nonspecific immune activation by inhibition of macrophage function may facilitate hepatic engraftment of islet allografts. The mechanisms mediating this effect are likely to include prevention of release of tumor necrosis factor-alpha, interleukin-1beta, and NO and interference with the rate of immune response to the islets.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
316-23
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9519734-Animals, pubmed-meshheading:9519734-Clodronic Acid, pubmed-meshheading:9519734-Cohort Studies, pubmed-meshheading:9519734-Diabetes Mellitus, Experimental, pubmed-meshheading:9519734-Gadolinium, pubmed-meshheading:9519734-Graft Survival, pubmed-meshheading:9519734-Hyaluronic Acid, pubmed-meshheading:9519734-Immunosuppression, pubmed-meshheading:9519734-Interleukin-1, pubmed-meshheading:9519734-Islets of Langerhans Transplantation, pubmed-meshheading:9519734-Macrophages, pubmed-meshheading:9519734-Microspheres, pubmed-meshheading:9519734-Nitrates, pubmed-meshheading:9519734-Nitrites, pubmed-meshheading:9519734-Rats, pubmed-meshheading:9519734-Rats, Inbred Lew, pubmed-meshheading:9519734-Rats, Sprague-Dawley, pubmed-meshheading:9519734-Time Factors, pubmed-meshheading:9519734-Transplantation, Heterotopic, pubmed-meshheading:9519734-Tumor Necrosis Factor-alpha
pubmed:year
1998
pubmed:articleTitle
Transplantation of allogeneic islets of Langerhans in the rat liver: effects of macrophage depletion on graft survival and microenvironment activation.
pubmed:affiliation
Diabetes Research Institute, Cell Transplant Center, University of Miami School of Medicine, Florida 33136, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't