Activation and proliferation signals in murine macrophages. Biochemical signals controlling the regulation of macrophage urokinase-type plasminogen activator activity by colony-stimulating factors and other agents.
Purified hematopoietic growth factors such as colony-stimulating factor-1 (CSF-1) or macrophage CSF, granulocyte-macrophage CSF, and interleukin-3 or multi-CSF, stimulate the urokinase-type plasminogen activator (u-PA) activity of murine bone marrow-derived macrophages (BMM) and resident peritoneal macrophages. Granulocyte-CSF was inactive. The increases in BMM u-PA activity were inhibited by the glucocorticoid dexamethasone, and by agents that raise intracellular cyclic adenosine monophosphate levels, including prostaglandin E2 and cholera toxin. These changes in u-PA activity were paralleled by corresponding changes in u-PA mRNA levels. Evidence was obtained for protein kinase C and phospholipase C-mediated stimulation of BMM u-PA activity and mRNA levels; however, no evidence was found for an involvement of Na+/H+ exchange or Na+, K(+)-ATPase activity, Ca2+ fluxes, or pertussis toxin-sensitive G proteins. Several findings point to a dissociation between macrophage u-PA expression and DNA synthesis.
Hamilton
J A
JA
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Australia.
Vairo
G
G
Knight
K R
KR
Cocks
B G
BG
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D005343:Fibrinolytic Agents / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010960:Plasminogen Activators / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D012964:Sodium / Q000493:pharmacokinetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D003115:Colony-Stimulating Factors; D005343:Fibrinolytic Agents; D007377:Interleukin-3; D012333:RNA, Messenger; D003208:Concanavalin A; D003907:Dexamethasone; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D002772:Cholera Toxin; D012964:Sodium; D000242:Cyclic AMP; D011493:Protein Kinase C; D010738:Type C Phospholipases; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D000254:Sodium-Potassium-Exchanging ATPase; D015232:Dinoprostone; D002118:Calcium