title: Stroma-mediated granulocyte-macrophage colony-stimulating factor (GM-CSF) control of myelopoiesis: spatial organisation of intercellular interactions.
abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the major cytokines involved in control of haemopoiesis both in bone marrow and in extramedullar sites. Its biological activity depends upon the composition and physicochemical properties of the microenvironment provided by the supporting stroma. GM-CSF activity is modulated and controlled by the stromal heparan-sulphate proteoglycans, but their optimal interaction occurs only at low pH. We questioned whether the microenvironment organisation of the interface between stroma and haemopoietic cells provides such conditions. We studied myeloid progenitor proliferation in contact with bone marrow-derived and extramedullar stromas using electron microscopy and selective labelling of pericellular components. We present evidence that, upon interaction, the two cell types reorganise their interface both in shape and molecular composition. Haemopoietic cells extend projections that considerably increase the area of intercellular contact, and stromal cells form lamellipodia and carry out a redistribution of membrane-associated sialylated glycoconjugates and proteoglycans. Such rearrangements lead to extensive capping of negatively charged molecules at the interface between the supporting stroma and the haemopoietic cells, leading potentially to a local decrease in pH. Our results indicate that the distribution of negative charges at the cellular interface may be responsible for the selectivity of cell response to GM-CSF.
authors.affiliation: Departamento de Histologia-Embriologia, Instituto de Ciências Biomédicas, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, 21941-970, Rio de Janeiro, Brazil. radovan@iq.ufrj.br
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.forename: Marcelo Alex
authors.initials: MA
authors.lastname: Carvalho
authors.forename: José Dias
authors.initials: JD
authors.lastname: Corrêa-Junior
authors.forename: Katia
authors.initials: K
authors.lastname: Arcanjo
authors.forename: Laurecir
authors.initials: L
authors.lastname: Gomes
authors.forename: Paulo Pinto
authors.initials: PP
authors.lastname: Joazeiro
authors.forename: Alex
authors.initials: A
authors.lastname: Balduino
authors.forename: Aline
authors.initials: A
authors.lastname: Wettreich
authors.forename: Tatiana
authors.initials: T
authors.lastname: Coelho-Sampaio
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D022081:Cell Surface Extensions / Q000648:ultrastructure; D002478:Cells, Cultured; D018920:Coculture Techniques; D003239:Connective Tissue Cells / Q000502:physiology; D005293:Ferritins / Q000032:analysis; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D019276:Glycocalyx / Q000737:chemistry / Q000648:ultrastructure; D006025:Glycosaminoglycans / Q000032:analysis / Q000302:isolation & purification / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000032:analysis; D051379:Mice; D008809:Mice, Inbred C3H; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008858:Microscopy, Phase-Contrast; D023461:Myeloid Progenitor Cells / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D038042:Myelopoiesis / Q000502:physiology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism; D009942:Organometallic Compounds / Q000032:analysis; D011485:Protein Binding; D011509:Proteoglycans / Q000032:analysis / Q000502:physiology; D011554:Pseudopodia / Q000648:ultrastructure; D012430:Ruthenium Red / Q000032:analysis / Q000494:pharmacology; D012542:Scattering, Radiation; D017154:Stromal Cells / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure
chemical_list: D006025:Glycosaminoglycans; D007211:Indoles; D009942:Organometallic Compounds; D011509:Proteoglycans; C010297:polycationic ferritin; D012430:Ruthenium Red; C015445:copper phthalocyanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005293:Ferritins; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid