title: Changes in intracellular Ca2+ levels induced by cytokines and P2 agonists differentially modulate proliferation or commitment with macrophage differentiation in murine hematopoietic cells.
abstract: The role of intracellular Ca2+ (Ca2+i) on hematopoiesis was investigated in long term bone marrow cultures using cytokines and agonists of P2 receptors. Cytokines interleukin 3 and granulocyte/macrophage colony stimulator factor promoted a modest increase in Ca2+i concentration ([Ca2+]i) with activation of phospholipase Cgamma, MEK1/2, and Ca2+/calmodulin kinase II. Involvement of protein kinase C was restricted to stimulation with interleukin 3. In addition, these cytokines promoted proliferation (20 times) and an increase in the Gr-1(-)Mac-1+ population with participation of gap junctions (GJ). Nevertheless ATP, ADP, and UTP promoted a large increase in [Ca2+]i, moderate proliferation (6 times), a reduction in the primitive Gr-1(-)Mac-1(-)c-Kit+ population, and differentiation into macrophages without participation of GJ. It is likely that Ca2+i participates as a regulator of hematopoietic signaling: moderate increases in [Ca2+]i would be related to cytokine-dependent proliferation with participation of GJ, whereas high increases in [Ca2+]i would be related to macrophage differentiation without maintenance of the primitive population.
authors.affiliation: Department of Biophysics, Federal University of São Paulo, Rua Botucatu 862, 04023-062 São Paulo, Brazil. jean@biofis.epm.br
authors.forename: Edgar J
authors.initials: EJ
authors.lastname: Paredes-Gamero
authors.forename: Carlos M M P
authors.initials: CM
authors.lastname: Leon
authors.forename: Radovan
authors.initials: R
authors.lastname: Borojevic
authors.forename: Maria E M
authors.initials: ME
authors.lastname: Oshiro
authors.forename: Alice T
authors.initials: AT
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017630:Connexins / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006413:Hematopoietic System / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism
chemical_list: D017630:Connexins; D016207:Cytokines; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium