Activation and proliferation signals in murine macrophages: relationships among c-fos and c-myc expression, phosphoinositide hydrolysis, superoxide formation, and DNA synthesis.
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-leucyl-phenylalanine (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.
Hamilton
J A
JA
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville.
Veis
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N
Bordun
A M
AM
Vairo
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Gonda
T J
TJ
Phillips
W A
WA
D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004789:Enzyme Activation / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006868:Hydrolysis; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D003115:Colony-Stimulating Factors; D010716:Phosphatidylinositols; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013481:Superoxides; D004247:DNA; D011493:Protein Kinase C