ATP-evoked intracellular Ca2+ responses in M-CSF differentiated human monocyte-derived macrophage are mediated by P2X4 and P2Y11 receptor activation

Janice A. Layhadi, Samuel J. Fountain

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Abstract

Tissues differentially secrete multiple colony stimulating factors under conditions of homeostasis and inflammation, orientating recruited circulating monocytes to differentiate to macrophage with differing functional phenotypes. Here, we investigated ATP-evoked intracellular Ca2+ responses in human macrophage differentiated with macrophage colony-stimulating factor (M-CSF). Extracellular ATP evoked (EC50 13.3 ± 1.4 µM) robust biphasic intracellular Ca2+ responses that showed a dependency on both metabotropic (P2Y) and ionotropic (P2X) receptors. qRT-PCR and immunocytochemistry revealed the expression of P2Y1, P2Y2, P2Y6, P2Y11, P2Y13, P2X1, P2X4, P2X5, and P2X7. Pharmacological analysis revealed contribution of only P2X4 and P2Y11 to the Ca2+ response evoked by maximal ATP concentrations (100 µM). This study reveals the contribution of P2X4 and P2Y11 receptor activation to ATP-evoked intracellular Ca2+ responses, and makes comparison with macrophage differentiated using granulocyte colony-stimulating factor (GM-CSF).

Original languageEnglish
Article number5113
JournalInternational Journal of Molecular Sciences
Volume20
Issue number20
DOIs
Publication statusPublished - 15 Oct 2019

Keywords

  • Calcium signaling
  • Inflammation
  • Macrophage
  • Purinergic

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