Activation and proliferation signals in murine macrophages: Relationships among c‐fos and c‐myc expression, phosphoinositide hydrolysis, superoxide formation, and DNA synthesis

Abstract

Murine bone marrow‐derived macrophages (BMM) undergo DNA synthesis in response to growth factors such as colony stimulating factor‐1 (CSF‐1) and granulocyte‐macrophage CSF (GM‐CSF). These macrophages can also be “activated,” but without subsequent DNA synthesis, by a number of other agents, including lipopolysaccharide (LPS), concanavalin A, zymosan, formyl‐methionyl‐leucylphenylalanine (FMLP), and the Ca²⁺ ionophore, A23187. When BMM are treated with a range of stimuli, there is some, although not perfect, correlation between transient elevations in both c‐myc mRNA and c‐fos mRNA levels and increases in DNA synthesis. However, enhanced DNA synthesis and oncogene expression are readily dissociated from rises in inositol phosphates and, by implication, phospholipase C‐mediated hydrolysis of phosphatidyl inositol 4,5‐bisphosphate. Superoxide formation in BMM can also be dissociated from the other responses and does not necessarily depend on protein kinase C activation.