title: Gangliosides of the stroma layer participate in the interferon-gamma receptor-dependent controls of myelopoiesis.
abstract: Stroma-mediated myelopoiesis depends upon growth-factors and an appropriate intercellular microenvironment, whose polarity is relevant for granulocyte-macrophage colony stimulating factor (GM-CSF) mediated myeloid cell proliferation. Here we have studied qualitative and quantitative aspects of ganglioside participation in controls of the microenvironment required to sustain myelopoiesis. We analysed ganglioside synthesis, expression and shedding by two primary liver stromal cell cultures isolated from wild type and interferon-gamma (IFNgamma) receptor knockout mice. The latter one has a higher capacity to sustain myelopoiesis. FDC-P1 myeloid growth factor-dependent cell line was used as the reporter system, monitoring the cell survival and proliferation that reflect the bio-availability and the activity of GM-CSF. Although the two stromal cells synthesised the same gangliosides their relative content was quite different. FDC-P1 proliferation decreased in cultures in which ganglioside synthesis was inhibited in the stroma, as well as in presence of stroma cell supernatants in which GM3 was neutralised by the anti-GM3 monoclonal antibody. Addition of exogenous GM3 reverted the inhibition and sustained proliferation of FDC-P1 cells. FDC-P1 cells do not accumulate GM3, but they are able to take up the stroma-produced sphingolipids. Thus, stroma has a double role in sustaining myelopoiesis, providing both growth factor(s) and ganglioside(s) required for the optimal stimulation of the myeloid cell proliferation, and the IFNgamma mediated stroma-dependent controls of myelopoiesis are determinant for this cell interaction.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600 anexo, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Claudia M B
authors.initials: CM
authors.lastname: Andrade
authors.forename: Ana L
authors.initials: AL
authors.lastname: Ziulkoski
authors.forename: Aline X S
authors.initials: AX
authors.lastname: dos Santos
authors.forename: Leonardo C
authors.initials: LC
authors.lastname: Boldrini
authors.forename: Vera M T
authors.initials: VM
authors.lastname: Trindade
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.forename: Fátima C R
authors.initials: FC
authors.lastname: Guma
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D018920:Coculture Techniques; D005679:G(M3) Ganglioside / Q000502:physiology; D005732:Gangliosides / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008099:Liver / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D038042:Myelopoiesis; D017471:Receptors, Interferon / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013107:Sphingolipids / Q000096:biosynthesis; D017154:Stromal Cells / Q000502:physiology*; D000096743:Interferon gamma Receptor
chemical_list: D005679:G(M3) Ganglioside; D005732:Gangliosides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017471:Receptors, Interferon; D013107:Sphingolipids; D000096743:Interferon gamma Receptor