Activation and proliferation signals in murine macrophages: Stimulation of Na+, K+‐ATPase activity by hemopoietic growth factors and other agents

Abstract

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, 12-0-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.