Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow / metabolism
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Bone Marrow Cells
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Calcium / metabolism
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Cell Division / drug effects
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Cell Division / physiology
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Cholera Toxin / pharmacology
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Colony-Stimulating Factors / pharmacology*
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Concanavalin A / pharmacology
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Cyclic AMP / metabolism
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DNA / metabolism
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Dexamethasone / pharmacology
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Dinoprostone / pharmacology
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Female
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Fibrinolytic Agents / metabolism*
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Gene Expression / drug effects
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Gene Expression / genetics
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Interleukin-3 / pharmacology
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Macrophage Activation / drug effects
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Macrophage Activation / physiology*
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Macrophage Colony-Stimulating Factor / pharmacology
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Macrophages / cytology
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Macrophages / metabolism
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Macrophages / physiology*
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Male
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Mice
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Mice, Inbred CBA
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Plasminogen Activators / genetics
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Plasminogen Activators / metabolism*
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Protein Kinase C / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Signal Transduction / genetics
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Signal Transduction / physiology*
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Sodium / pharmacokinetics
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Sodium-Potassium-Exchanging ATPase / metabolism
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Type C Phospholipases / metabolism
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Urokinase-Type Plasminogen Activator / genetics
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Urokinase-Type Plasminogen Activator / metabolism*
Substances
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Colony-Stimulating Factors
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Fibrinolytic Agents
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Interleukin-3
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RNA, Messenger
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Concanavalin A
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Dexamethasone
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Macrophage Colony-Stimulating Factor
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Granulocyte-Macrophage Colony-Stimulating Factor
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DNA
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Cholera Toxin
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Sodium
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Cyclic AMP
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Protein Kinase C
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Type C Phospholipases
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Plasminogen Activators
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Urokinase-Type Plasminogen Activator
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Sodium-Potassium-Exchanging ATPase
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Dinoprostone
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Calcium