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Rich66 · 06-20-2009, 08:40 PM

1: J Biol Chem. 2009 Jun 15. [Epub ahead of print] Links: Cytotoxicity mediated by the FASL-activated apoptotic pathway in stem cells.

Mazar J, Thomas M, Bezrukov L, Chanturia A, Pekkurnaz G, Yin S, Kuznetsov SA, Robey PG, Zimmerberg J.
National Institutes of Health, United States.
While it is now clear that human bone marrow stromal cells (BMSCs) can be immunosuppressive and escape cytotoxic lymphocytes (CTLs) in vitro and in vivo, the mechanisms of this phenomenon remain controversial. Here, we test the hypothesis that BMSCs suppress immune responses by Fasmediated apoptosis of activated lymphocytes, and find both Fas and FasL expression by primary BMSCs. Jurkat cells, or activated lymphocytes, were each killed by BMSCs after 72 hrs of co-incubation. In comparison, the cytotoxic effect of BMSCs on non-activated lymphocytes and on caspase 8 -/- Jurkat cells was extremely low. Fas/Fc fusion protein strongly inhibited BMSC-induced lymphocyte apoptosis. Although we detected a high level of Fas expression in BMSCs, stimulation of Fas with anti-Fas antibody did not result in the expected BMSC apoptosis, regardless of concentration, suggesting a disruption of the Fas activation pathway. Thus BMSCs may have an endogenous mechanism to evade Fas-mediated apoptosis. Cumulatively, these data provide a parallel between adult stem/progenitor cells and cancer cells, consistent with the idea that stem/progenitor cells can use FasL to prevent lymphocyte attack by inducing lymphocyte apoptosis during the regeneration of injured tissues.
PMID: 19531476 [PubMed - as supplied by publisher]

06-20-2009, 08:40 PM	#28
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	1: J Biol Chem. 2009 Jun 15. [Epub ahead of print] Links Cytotoxicity mediated by the FASL-activated apoptotic pathway in stem cells. Mazar J, Thomas M, Bezrukov L, Chanturia A, Pekkurnaz G, Yin S, Kuznetsov SA, Robey PG, Zimmerberg J. National Institutes of Health, United States. While it is now clear that human bone marrow stromal cells (BMSCs) can be immunosuppressive and escape cytotoxic lymphocytes (CTLs) in vitro and in vivo, the mechanisms of this phenomenon remain controversial. Here, we test the hypothesis that BMSCs suppress immune responses by Fasmediated apoptosis of activated lymphocytes, and find both Fas and FasL expression by primary BMSCs. Jurkat cells, or activated lymphocytes, were each killed by BMSCs after 72 hrs of co-incubation. In comparison, the cytotoxic effect of BMSCs on non-activated lymphocytes and on caspase 8 -/- Jurkat cells was extremely low. Fas/Fc fusion protein strongly inhibited BMSC-induced lymphocyte apoptosis. Although we detected a high level of Fas expression in BMSCs, stimulation of Fas with anti-Fas antibody did not result in the expected BMSC apoptosis, regardless of concentration, suggesting a disruption of the Fas activation pathway. Thus BMSCs may have an endogenous mechanism to evade Fas-mediated apoptosis. Cumulatively, these data provide a parallel between adult stem/progenitor cells and cancer cells, consistent with the idea that stem/progenitor cells can use FasL to prevent lymphocyte attack by inducing lymphocyte apoptosis during the regeneration of injured tissues. PMID: 19531476 [PubMed - as supplied by publisher]