Agonistic anti-Fas antibodies induce glomerular cell apoptosis in mice in vivo.
Recent studies suggest that apoptotic cell death regulates the cell complement in glomerular diseases. However, little is-known about the factors that promote glomerular cell apoptosis. Activation of the Fas receptor by the Fas ligand or agonistic antibodies triggers apoptosis in some cell types that express Fas. Cultured human mesangial cell are among the cells that undergo apoptosis upon Fas activation, but it is unclear whether mesangial cells are sensitive to death induced by Fas in vivo. We have now explored the role of Fas in experimental glomerular injury. Murine mesangial cells in culture express fas and undergo apoptosis when stimulated with the Jo2 agonistic anti-Fas mAb. A fas mRNA transcript is present in normal murine kidney and freshly isolated glomeruli. Balb-c mice developed hematuria and proteinuria within 24 hours of the intraperitoneal injection of 10 micrograms Jo2 anti-Fas mAb. In addition to liver cell apoptosis, glomerular cell apoptosis and mesangial cell depletion were evident in the kidney at three hours and more pronounced at 24 hours. Glomerular and liver injury were not prevented by decomplementation. These data suggest that Fas activation in vivo by specific antibodies induces glomerular and mesangial cell apoptosis in mice.
González-Cuadrado
S
S
Laboratorio de Nefrología, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Lorz
C
C
García del Moral
R
R
O'Valle
F
F
Alonso
C
C
Ramiro
F
F
Ortiz-González
A
A
Egido
J
J
Ortiz
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000473:pathology / Q000502:physiology; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019014:fas Receptor