Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1997-11-21
pubmed:abstractText
Renal transplant rejection is characterized by an influx of mononuclear cells in the tubulointerstitial area. Recent studies indicate that tubular damage during graft rejection is dependent, at least in part, on apoptosis. It is thought that apoptosis may be induced by the mononuclear cell infiltrate via the perforin/granzyme or the Fas/Fas ligand pathway. Fas is a 43-kD member of the tumor necrosis factor receptor family, and ligation results in apoptosis of the Fas-bearing cell. The present study analyzes whether Fas is expressed on human tubular epithelial cells in situ and in vitro. It was found that 50 to 70% of the tubules in renal tissue exhibited a positive staining for Fas. To further study the occurrence of Fas on tubular cells, eight different primary proximal tubular epithelial cell (PTEC) lines were analyzed for Fas expression. More than 90% of the PTEC were positive for Fas, and treatment with IFN-gamma resulted in an even higher expression. To determine whether Fas ligation resulted in apoptosis of PTEC in culture, PTEC were incubated with two different anti-Fas antibodies, which were able to induce apoptosis in Jurkat cells. No apoptotic PTEC were observed after Fas ligation, as determined by morphological staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis. Simultaneous CD40 and Fas ligation, or treatment with IFN-gamma before Fas ligation, also did not result in the induction of apoptosis. Fas ligation did not result in proliferation or activation of PTEC, as measured by interleukin-8 production. Apoptotic PTEC could only be detected when the cells were incubated with both anti-Fas antibodies and cycloheximide, resulting in up to 92% apoptotic cells. This study demonstrates that although renal tubular epithelial cells express Fas, they appear to be resistant to Fas-mediated apoptosis, suggesting that Fas-mediated apoptosis does not play a role in the induction of apoptosis during renal transplant rejection.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1517-24
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9335379-Animals, pubmed-meshheading:9335379-Antigens, CD95, pubmed-meshheading:9335379-Apoptosis, pubmed-meshheading:9335379-Base Sequence, pubmed-meshheading:9335379-Cell Division, pubmed-meshheading:9335379-Cell Line, pubmed-meshheading:9335379-Cycloheximide, pubmed-meshheading:9335379-DNA Primers, pubmed-meshheading:9335379-Epithelial Cells, pubmed-meshheading:9335379-Gene Expression, pubmed-meshheading:9335379-Graft Rejection, pubmed-meshheading:9335379-Humans, pubmed-meshheading:9335379-Interleukin-8, pubmed-meshheading:9335379-Jurkat Cells, pubmed-meshheading:9335379-Kidney Transplantation, pubmed-meshheading:9335379-Kidney Tubules, Proximal, pubmed-meshheading:9335379-Ligands, pubmed-meshheading:9335379-Mice, pubmed-meshheading:9335379-Polymerase Chain Reaction, pubmed-meshheading:9335379-Protein Synthesis Inhibitors
pubmed:year
1997
pubmed:articleTitle
Expression and function of Fas (CD95) on human renal tubular epithelial cells.
pubmed:affiliation
Department of Nephrology, Leiden University Hospital, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't