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Regulation of plasminogen activator secretion, interferon induction and proliferation in murine macrophages
Abstract:
The purpose of this work was to study the interrelationship of proliferation and secretion of plasminogen activator (PA) and interferon (IFN) by murine macrophages. For induction of macrophage proliferation and secretion of PA, concanavalin A (Con A) was used. Secretion of IFN was induced by polyinosinic polycytidylic acid complex. The glucocorticoid dexamethasone acetate (DA) (10(-6)-10(9) M) inhibited Con A-stimulated secretion of PA and synthesis of DNA as evaluated by incorporation of [3H]thymidine. DA did not inhibit IFN induction. Preincubating macrophages with DA for 45 h reduced basal proliferation and secretion of PA but did not reduce responsiveness to Con A. Also retinoic acid, a modulator of carcinogenesis was used in inhibition studies because of its known antagonistic effects on lymphocyte mitogenesis. In macrophages a biphasic effect of retinoic acid (1 X 10(-5) - 5 X 10(-5)M) was found: (a) inhibition of DNA synthesis and secretion of PA during the first 45 h of incubation, and (b) enhancement of DNA synthesis (but not PA secretion) after 72 h. Secretion of IFN was not affected. It is suggested that secretion of PA but not IFN is linked to cell cycle traverse of macrophages.
Insights
Glucocorticoids and retinoic acid differentially affect macrophage functions. Dexamethasone acetate inhibits proliferation and plasminogen activator secretion, while retinoic acid shows biphasic effects, suggesting plasminogen activator secretion is cell cycle-dependent.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophages play crucial roles in immune responses and tissue remodeling.
- Plasminogen activator (PA) and interferon (IFN) are key secreted proteins involved in various cellular processes.
Purpose of the Study:
- To investigate the relationship between murine macrophage proliferation and the secretion of plasminogen activator (PA) and interferon (IFN).
- To examine the effects of dexamethasone acetate (DA) and retinoic acid on these macrophage functions.
Main Methods:
- Macrophage proliferation and PA secretion were induced using concanavalin A (Con A).
- IFN secretion was induced by polyinosinic polycytidylic acid complex.
- The impact of dexamethasone acetate and retinoic acid on DNA synthesis (proliferation) and protein secretion was assessed using [3H]thymidine incorporation.
Main Results:
- Dexamethasone acetate (DA) inhibited Con A-stimulated PA secretion and DNA synthesis but did not affect IFN induction.
- Pre-incubation with DA reduced basal proliferation and PA secretion but not Con A responsiveness.
- Retinoic acid exhibited a biphasic effect: initial inhibition of DNA synthesis and PA secretion, followed by enhancement of DNA synthesis (but not PA secretion) after 72 hours.
- Neither DA nor retinoic acid affected IFN secretion.
Conclusions:
- Macrophage secretion of PA is linked to the cell cycle, whereas IFN secretion is not.
- These findings highlight distinct regulatory mechanisms for PA and IFN secretion in macrophages.
- The differential effects of DA and retinoic acid provide insights into modulating macrophage inflammatory and tissue remodeling functions.