Induction of apoptosis in bone marrow cells by gangliosides produced by a T cell lymphoma

The present study was conducted to investigate the mode of cell death of bo ne marrow cells (BMC) treated in vivo or in vitro with gangliosides (DLG) d erived from a T cell lymphoma, designated as Dalton's lymphoma (DL). BMC un dergoing cell death showed morphological features characteristic to apoptos is such as cell shrinkage, plasma membrane blebbing and densely stained chr omatin. DLG-induced apoptosis was further confirmed by analysis of DNA from DLG-treated BMC by flow cytometry and agarose gel electrophoresis which sh owed an increase in hypodiploid DNA and internucleosomal DNA cleavage, resp ectively. Immunoblotting of p53 and Bar demonstrated an increase in the lev els of p53 and Bar proteins. BMC treated with DLG also showed translocation of NF-kappa B protein into the nucleus. Antibodies to ganglioside G(D3), a constituent of DLG, neutralized the effect of DLG. Further, supplementatio n of DLG-containing BMC cultures with granulocyte macrophage-colony stimula ting factor (GM-CSF) or macrophage-colony stimulating factor (M-CSF) preven ted the apoptosis-inducing action of DLG. (C) 2000 Elsevier Science B.V. Al l rights reserved.