Gangliosides of myelosupportive stroma cells are transferred to myeloid progenitors and are required for their survival and proliferation.
In previous studies, we have shown that the myelopoiesis dependent upon myelosupportive stroma required production of growth factors and heparan-sulphate proteoglycans, as well as generation of a negatively charged sialidase-sensitive intercellular environment between the stroma and the myeloid progenitors. In the present study, we have investigated the production, distribution and role of gangliosides in an experimental model of in vitro myelopoiesis dependent upon AFT-024 murine liver-derived stroma. We used the FDC-P1 cell line, which is dependent upon GM-CSF (granulocyte/macrophage colony-stimulating factor) for both survival and proliferation, as a reporter system to monitor bioavailability and local activity of GM-CSF. G(M3) was the major ganglioside produced by stroma, but not by myeloid cells, and it was required for optimal stroma myelosupportive function. It was released into the supernatant and selectively incorporated into the myeloid progenitor cells, where it segregated into rafts in which it co-localized with the GM-CSF-receptor alpha chain. This ganglioside was also metabolized further by myeloid cells into gangliosides of the a and b series, similar to endogenous G(M3). In these cells, G(M1) was the major ganglioside and it was segregated at the interface by stroma and myeloid cells, partially co-localizing with the GM-CSF-receptor alpha chain. We conclude that myelosupportive stroma cells produce and secrete the required growth factors, the cofactors such as heparan sulphate proteoglycans, and also supply gangliosides that are transferred from stroma to target cells, generating on the latter ones specific membrane domains with molecular complexes that include growth factor receptors.
Ziulkoski
Ana L
AL
Laboratório de Bioquímica e Biologia Celular de Lipídios, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Andrade
Cláudia M B
CM
Crespo
Pilar M
PM
Sisti
Elisa
E
Trindade
Vera M T
VM
Daniotti
Jose L
JL
Guma
Fátima C R
FC
Borojevic
Radovan
R
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D005732:Gangliosides / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008099:Liver / Q000166:cytology; D051379:Mice; D009025:Morpholines; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*
D005732:Gangliosides; D009025:Morpholines; C033110:RV 538; D016178:Granulocyte-Macrophage Colony-Stimulating Factor