Anti-Fas antibodies induce cytolysis and apoptosis in cultured human mesangial cells

Silvia González-Cuadrado, María José López-Armada, Carmen Gómez-Guerrero, Dolores Subirá, Almudena Garcia-Sahuquillo, Arturo Ortiz-Gonzalez, Eric G. Neilson, Jesús Egido, Alberto Ortiz*

*Corresponding author for this work

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Death of renal cells often occurs during the acute and resolution phases of some forms of glomerulonephritis. The apoptotic Fas protein belongs to a recently described family of cytokine receptors with similarities to tumor necrosis factor (TNF) receptors, and may contribute to the necrobiology of renal cells. Fas transduces a signal for apoptosis in sensitive cells after binding by specific antibodies or following contact with natural Fas ligand. We have studied Fas in cultured human mesangial cells. Cytoflurography demonstrated Fas expression on the surface of human mesangial cells that was increased by stimulation with interferon gamma (IFNγ). Agonistic anti-human Fas antibodies were cytotoxic to these cells. Cytotoxicity was time- and dose-dependent, and was modulated by pre-stimulation of the mesangial cells with IFNγ and/or by co-treatment with actinomycin-D. Mesangial cell death following exposure to anti-Fas antibodies has features consistent with apoptosis, such as internucleosomal DNA fragmentation, nuclear shrinkage and condensation, and decreased DNA content. These data suggest that Fas and its ligand could play a mechanistic role in human glomerular cell injury.

Original languageEnglish (US)
Pages (from-to)1064-1070
Number of pages7
JournalKidney international
Volume49
Issue number4
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Nephrology

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    González-Cuadrado, S., López-Armada, M. J., Gómez-Guerrero, C., Subirá, D., Garcia-Sahuquillo, A., Ortiz-Gonzalez, A., Neilson, E. G., Egido, J., & Ortiz, A. (1996). Anti-Fas antibodies induce cytolysis and apoptosis in cultured human mesangial cells. Kidney international, 49(4), 1064-1070. https://doi.org/10.1038/ki.1996.155