Activation and proliferation signals in murine macrophages: stimulation of Na+,K+-ATPase activity by hemopoietic growth factors and other agents.
Purified colony stimulating factor (CSF-1) stimulates the Na+,K+-ATPase activity of murine bone marrow-derived macrophages (BMM) and resident peritoneal macrophages (RPM) measured as ouabain-sensitive 86Rb+ uptake. Similar concentrations of CSF-1 stimulate the Na+,K+-ATPase activity and DNA synthesis in BMM whilst ouabain, a specific inhibitor of the Na+,K+-ATPase, also inhibits this CSF-1-mediated DNA synthesis. Other purified hemopoietic growth factors, granulocyte-macrophage CSF (GM-CSF) and interleukin-3 (IL-3), and the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), even though differing in their mitogenic capabilities, are also stimulators of the Na+,K+-ATPase activity in BMM and RPM. The non-mitogenic agents, lipopolysaccharide (LPS) and Concanavalin A (Con A), are also active. CSF-1 stimulation of the Na+,K+-ATPase was shown to be dependent on elevation of intracellular Na+ via an amiloride sensitive Na+-channel, most likely representing Na+/H+ exchange activity. Such stimulation of Na+,K+-ATPase activity via activation of the Na+/H+ exchange appears to be a necessary but insufficient early macrophage response for subsequent DNA synthesis.
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D002455:Cell Division; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D006133:Growth Substances / Q000494:pharmacology*; D006410:Hematopoiesis; D006859:Hydrogen / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007474:Ion Exchange; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010042:Ouabain / Q000494:pharmacology; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007473:Ion Channels; D010042:Ouabain; D006859:Hydrogen; D004247:DNA; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D013755:Tetradecanoylphorbol Acetate