title: GD1a modulates GM-CSF-induced cell proliferation.
abstract: Gangliosides have been extensively described to be involved in the proliferation and differentiation of various cell types, such including hematopoietic cells. Our previous studies on murine models of stroma-mediated myelopoiesis have shown that gangliosides are required for optimal capacity of stromal cells to support proliferation of myeloid precursor cells, being shed to the supernatant and selectively incorporated into myeloid cell membranes. Here we describe the effect of gangliosides on the specific granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced proliferation. For that, we used the monocytic FDC-P1 cell line, which is dependent upon GM-CSF for survival and proliferation. Cells were cultured in the presence of GM-CSF and exogenous gangliosides (GM3, GD1a or GM1) or in the absence of endogenous ganglioside synthesis by the use of a ceramide-synthase inhibitor, D-PDMP. We observed that exogenous addition of GD1a enhanced the GM-CSF-induced proliferation of the FDC-P1 cells. Also, we detected an increase in the expression of the α isoform of the GM-CSF receptor (GMRα) as well as of the transcription factor C/EBPα. On the contrary, inhibition of glucosylceramide synthesis was accompanied by a decrease in cell proliferation, which was restored upon the addition of exogenous GD1a. We also show a co-localization of GD1a and GMR by immunocytochemistry. Taken together, our results suggest for the first time that ganglioside GD1a play a role on the modulation of GM-CSF-mediated proliferative response, which might be of great interest not only in hematopoiesis, but also in other immunological processes, Alzheimer disease, alveolar proteinosis and wherever GM-CSF exerts its effects.
authors.affiliation: Laboratório de Bioquímica e Biologia Celular de Lipídios, Depto Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. alinexss@gmail.com
authors.forename: A X S
authors.initials: AX
authors.lastname: Santos
authors.forename: J E
authors.initials: JE
authors.lastname: Maia
authors.forename: P M
authors.initials: PM
authors.lastname: Crespo
authors.forename: L F
authors.initials: LF
authors.lastname: Pettenuzzo
authors.forename: J L
authors.initials: JL
authors.lastname: Daniotti
authors.forename: F M
authors.initials: FM
authors.lastname: Barbé-Tuana
authors.forename: L M
authors.initials: LM
authors.lastname: Martins
authors.forename: V M T
authors.initials: VM
authors.lastname: Trindade
authors.forename: R
authors.initials: R
authors.lastname: Borojevic
authors.forename: F C R
authors.initials: FC
authors.lastname: Guma
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003720:Densitometry; D005455:Fluorescent Antibody Technique; D005679:G(M3) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000096:biosynthesis / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D018613:Microscopy, Confocal; D009025:Morpholines / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D012995:Solubility / Q000187:drug effects
chemical_list: D005679:G(M3) Ganglioside; D005732:Gangliosides; D009025:Morpholines; D020033:Protein Isoforms; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; C021298:ganglioside, GD1a; C033110:RV 538; D016178:Granulocyte-Macrophage Colony-Stimulating Factor