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Prostaglandin E synthesis and release by murine macrophages and human monocytes after in vitro treatment with
Abstract:
Prostaglandins of the E series (PGE), produced by mononuclear phagocytes, have many biological activities and are involved in the regulation of myelopoiesis and of the cytotoxic activities of macrophage (M phi) and natural killer (NK) cells. Since one of the possible effects of biological response modifiers (BRMs) on immune regulation might be modulation of PGE production, resident peritoneal murine M phi (mM phi) and elutriated human blood monocytes (hM) were incubated with BRMs and the supernatants were then assayed for PGE. Control mM phi produced about 4.9 ng PGE/10(5) mM phi over a 24 hr period. Lipopolysaccharide (LPS, 1-5 micrograms/ml), polyinosinic-polycytidylic acid complexed with poly-L-lysine (Poly ICLC, 0.1-10 micrograms/ml) and murine alpha, beta-interferon, (IFN, 10-1000 U/ml) all caused a highly significant increase in PGE-secretion. BM41.332, a 2-cyanoaziridine (25-50 micrograms/ml), was found to be less stimulatory, whereas the pyran copolymer MVE-2 (25-50 micrograms/ml), and Azimexone (25-50 micrograms/ml) had marginal effects on PGE-production. Kinetic studies showed that the plateau of PGE-production by mM phi occurred during the first 24 hr of incubation, and mM phi which were washed after a 24 hr incubation period could not be restimulated to produce more PGE. PGE release by hM was increased after stimulation with LPS, Poly IGLC and BM41.332, whereas human IFNs (alpha and beta) induced a slight decrease in PGE production. As in the murine studies, Azimexone and MVE-2 had no detectable effect. The ability of some BRMs to augment PGE-secretion by mM phi and hM may contribute to their negative effects on host responses, such as suppression of NK cell activity.
Insights
Biological response modifiers (BRMs) can increase prostaglandin E (PGE) production by immune cells. This elevated PGE may suppress natural killer (NK) cell activity, potentially impacting host immune responses.
Area of Science:
- Immunology
- Pharmacology
Background:
- Prostaglandins E (PGE) are crucial mediators produced by mononuclear phagocytes.
- PGE regulates myelopoiesis and the cytotoxic functions of macrophages (M phi) and natural killer (NK) cells.
- Biological response modifiers (BRMs) may influence immune regulation by modulating PGE production.
Purpose of the Study:
- To investigate the effect of various BRMs on PGE production in murine macrophages (mM phi) and human monocytes (hM).
- To determine if BRM-induced changes in PGE secretion correlate with potential negative effects on host immune responses, such as NK cell activity.
Main Methods:
- Resident peritoneal murine M phi and elutriated human blood monocytes were incubated with different BRMs.
- Supernatants were collected and assayed for PGE levels.
- BRMs tested included Lipopolysaccharide (LPS), Poly ICLC, Interferons (IFN), BM41.332, MVE-2, and Azimexone.
Main Results:
- LPS, Poly ICLC, and murine IFN significantly increased PGE secretion by mM phi.
- BM41.332 showed less stimulation, while MVE-2 and Azimexone had marginal effects on mM phi PGE production.
- LPS, Poly ICLC, and BM41.332 increased PGE release by human monocytes (hM), whereas human IFNs slightly decreased it. Azimexone and MVE-2 had no effect on hM.
Conclusions:
- Certain BRMs, including LPS and Poly ICLC, augment PGE secretion in both murine and human phagocytes.
- This augmentation of PGE production by BRMs may contribute to immunosuppressive effects, such as the suppression of NK cell activity.
- Understanding BRM-mediated PGE modulation is important for evaluating their impact on host immune defenses.