Changes in Intracellular Ca2+ Levels Induced by Cytokines and P2 Agonists Differentially Modulate Proliferation or Commitment with Macrophage Differentiation in Murine Hematopoietic Cells
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2008-11-14
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Paredes-Gamero, Edgar Julian [UNIFESP]
Leon, Carlos M. M. P. [UNIFESP]
Borojevic, Radovan
Oshiro, Maria Etsuko Miyamoto [UNIFESP]
Ferreira, Alice Teixeira [UNIFESP]
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The role of intracellular Ca2+ (Ca-i(2+)) 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 Ca-i(2+) concentration ([Ca2+](i)) with activation of phospholipase C gamma, 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 Ca-i(2+) 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.
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Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 283, n. 46, p. 31909-31919, 2008.