
Fas on renal parenchymal cells does not promote autoimmune nephritis in MRL mice.
BACKGROUND: Although Fas on pancreatic islets promotes autoimmune diabetes in mice, the role of Fas expression on kidney parenchymal cells during autoimmune disease is unknown. METHODS: To determine whether Fas on renal parenchymal cells promotes autoimmune renal destruction, we compared apoptosis and pathology in Fas-intact and Fas-deficient kidneys in an autoimmune milieu. For this purpose, we transplanted single, normal kidneys from MRL-++ (Fas-intact) mice (3 months of age) into age-matched, congenic MRL-Faslpr (Fas-deficient) recipients after removal of nephritic kidneys. These Fas-intact kidneys were compared with Fas-deficient nephritic kidneys. RESULTS: There is a progressive increase of FasL on kidney-infiltrating cells and Fas and FasL on renal parenchymal cells in MRL-++ kidneys during engraftment (0, 2, 4-6, and 8 weeks). By comparison, we detected an increase in FasL in MRL-Faslpr kidneys (3 to 5 months of age), whereas Fas was not detectable. The engagement of T cells bearing FasL with Fas expressing tubular epithelial cells (TECs) induced TEC apoptosis in vitro. However, apoptosis and pathology were similar in kidneys (MRL-++, 8 weeks postengraftment vs. MRL-Faslpr, 5 months) with equivalent amounts of FasL-infiltrating cells or FasL TECs, regardless of Fas on renal parenchymal cells. CONCLUSION: The expression of Fas on renal parenchymal cells does not increase apoptosis or promote renal disease in MRL-++ mice. We speculate that the autoimmune milieu evokes mechanisms that mask, counter, or pre-empt Fas-FasL-initiated apoptosis in MRL kidneys.
Duke Scholars
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Related Subject Headings
- fas Receptor
- Urology & Nephrology
- Reverse Transcriptase Polymerase Chain Reaction
- Nephritis
- Mice, Inbred MRL lpr
- Mice, Congenic
- Mice
- Membrane Glycoproteins
- Kidney Transplantation
- Immunohistochemistry
Citation

Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- fas Receptor
- Urology & Nephrology
- Reverse Transcriptase Polymerase Chain Reaction
- Nephritis
- Mice, Inbred MRL lpr
- Mice, Congenic
- Mice
- Membrane Glycoproteins
- Kidney Transplantation
- Immunohistochemistry