Prostaglandin Production by Macrophages and the Effect of Anti‐inflammatory Drugs

Bray, M.A.; Gordon, Duncan A.

doi:10.1111/j.1476-5381.1978.tb17276.x

Cited by 86 publications

(29 citation statements)

References 48 publications

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“…Other work from our laboratory has demonstrated that monocytes directly resorb both devitalized bones by a mechanism which is not mediated by the action of osteoclasts (25) and live bones through an osteoclast-mediated mechanism which is prostaglandin-dependent (26). There is also other evidence which suggests that monocytes and macrophages synthesize and release PGs (27)(28)(29), collagenase (30), and hydrolytic enzymes (31), which are all capable of resorbing bone or degrading bone matrix. It is also possible that circulating mononuclear cells may transform or differentiate into osteoclasts (32).…”

Section: Discussionmentioning

confidence: 99%

Monocytes regulate osteoclast-activating factor production by releasing prostaglandins.

Yoneda¹,

Mundy²

1979

The Journal of Experimental Medicine

129

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Osteoclast-activating factor (OAF), a powerful stimulator of osteoclastic bone resorption, is released by peripheral blood mononuclear cells on exposure to phytohemagglutinin (PHA) or a specific antigen to which the leukocytes have been previously exposed. Both lymphocytes and monocytes are required in the leukocyte population for OAF release to occur. In this study we examined the relationship between the lymphocyte and monocyte in OAF production. Biological activity, as a result of OAF, was assessed by a bioassay based on the release of previously incorporated 45Ca from fetal rodent long bones in organ culture. We found that an enriched lymphocyte population depleted of monocytes by serial adherence does not release OAF after stimulation with PHA, although the cells are activated as assessed by [3H]thymidine and 3H-amino acid incorporation. When conditioned media harvested from adherent cells which did not contain OAF was added to the enriched lymphocytes, OAF release occurred. Media harvested from adherent cells which were cultured with indomethacin (10 microM), an inhibitor of prostaglandin synthesis, did not permit OAF release by activated lymphocytes. When PGE1 and PGE2 (0.1 microM) were added exogenously to the enriched lymphocyte population, OAF release occurred after stimulation with PHA. These results indicate that, (a) the activated lymphocyte is the cell or origin of OAF, (b) prostaglandins produced by monocytes are necessary for OAF production by activated lymphocytes, and (c) monocyte prostaglandins can influence bone resorption indirectly by regulating OAF production as well as directly by osteoclast activation. The interactions of OAF and prostaglandins at bone resorbing sites may be important in inflammatory and neoplastic diseases associated with bone destruction.

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Section: Discussionmentioning

confidence: 99%

Monocytes regulate osteoclast-activating factor production by releasing prostaglandins.

Yoneda¹,

Mundy²

1979

The Journal of Experimental Medicine

129

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“…We show that mobilization of cytoplasmic cAMP is likely one of the main mediators for PGE 2 activity since forskolin and the cAMP analogs, db-cAMP and 8-bromo-cAMP, could mimic the effect of PGE 2 Interestingly, cAMP induction decreases lipopolysaccharide (LPS)-and TNF-mediated NFkB-activation in a variety of experimental systems, resulting in reduced secretion of cytokines, including IL-12. [53][54][55][56][57][58][59] It is therefore tempting to speculate on the involvement of these 2 antagonistic pathways (both stress induced) in the regulation of DC differentiation. However, it is intriguing that the same PGE 2 signal that enhances TNF-␣-and IFN-␣-induced MoDC maturation simultaneously inhibits CD40L/E coliinduced cytokine secretion.…”

Section: Discussionmentioning

confidence: 99%

Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets

Luft

Jefford

Luetjens

et al. 2002

Blood

324

333

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Migration of antigen (Ag)-loaded dendritic cells (DCs) from sites of infection into draining lymphoid tissues is fundamental to the priming of T-cell immune responses. We evaluated monocyte-derived DCs (MoDCs) and peripheral blood DCs (PBDCs) to respond to proinflammatory mediators, CD40L, and intact bacteria. All classes of stimuli induced DC phenotypic maturation. However, for MoDCs, only prostaglandin E 2 (PGE 2 )-containing stimuli induced migratory-type DCs. Thus, immature MoDCs that encountered proinflammatory cytokines or CD40L or intact bacteria in the presence of PGE 2 acquired migratory capacity but secreted low levels of cytokines. Conversely, MoDCs that encountered pathogens or CD40L alone become nonmigratory cytokine-secreting cells (proinflammatory type). Interestingly, both migratoryand proinflammatory-type DCs expressed equivalent levels of chemokine receptors, suggesting that the role of PGE 2 was to switch on migratory function. We demonstrate that PGE 2 induces migration via the E-prostanoid 2/E-prostanoid 4 (EP 2 /EP 4 ) receptors and the cAMP pathway. Finally, migratory-type MoDCs stimulated T-cell proliferation and predominantly IL-2 secretion, whereas proinflammatory-type MoDCs induced IFN-␥ production. In contrast, CD1b/c ؉ PBDC rapidly acquired migratory capacity irrespective of the class of stimulus encountered and secreted low levels of cytokines. This suggests that not all mature stages of DCs are destined to migrate to lymphoid organs and that the sequence in which stimuli are encountered significantly affects which functions are expressed. Thus, certain immature DC subsets recruited from the resting precursor pool may have multiple functional fates that play distinct roles during the induction and effector phases of the immune response. These findings have important implications for the clinical utility

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“…Initial studies, which used cell-free systems, failed to demonstrate any effect of antiinflammatory steroids on PG production (1,3,4). Recently, however, evidence was obtained that glucocorticoids decrease PG production in different in vitro systems via inhibition ofphospholipase activity (5)(6)(7)(8)(9)(10)(11)(12)(13). Although this action of glucocorticoids seems to be fairly reproducible in in vitro systems, especially with high doses of steroids, almost no data are available on the effect of glucocorticoids on PG synthesis in vivo.…”

Section: Introductionmentioning

confidence: 99%

Effect of dexamethasone on in vivo prostanoid production in the rabbit.

Náray-Fejes-Tóth¹,

Fejes-Tóth²,

Fischer³

et al. 1984

J. Clin. Invest.

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Abstract. To investigate the effects of antiinflammatory steroids on in vivo prostaglandin production, urinary excretion rates of six different cyclo-oxygenase products were determined before, during, and after the administration of dexamethasone (1 mg/kg per d). Urine was collected in metabolism cages and was analyzed for prostaglandins E2 and F2a (PGE2 and PGF2a,) by radioimmunoassay after open-column chromatography; 6-ketoprostaglandin Fla (6-keto-PGFIa) and thromboxane B2 (TxB2) were determined by radioimmunoassay after organic solvent extraction and reversed-phase high performance liquid chromatography; 7a-hydroxy-5,1 1-diketo-tetranorprostane-1,16-dioic acid (PGE-M) and 5a,7a-dihydroxy-11 -keto-tetranorprostane-1,16-dioicacid (PGF-M), the major urinary metabolites of prostaglandins E and F, were determined by gas chromatography-mass spectrometry and by radioimmunoassay, respectively. Dexamethasone failed to cause a statistically significant change in the excretion rate of PGE2 (control, 250.4±40.8; dexamethasone, 297.6±78.7 ng/kg per d).In contrast, PGF2, excretion decreased during administration of dexamethasone (from 1,036±228 to 449±158 ng/kg per d; P < 0.05). The urinary excretion rates of 6-keto-PGFia, TxB2, PGE-M, and PGF-M were not significantly altered by dexamethasone. (Control and dexamethasone values were, respectively, 63.6±7.9 and 103.5±17.9 ng/kg per d for 6-keto-PGFIa; 13.0±3.0 and 14.8±2.1 ng/kgperd for TxB2; 1,251+217 and 1,905±573 ng/kg per d for PGE-M; and 4,131±611 and 4,793±600 ng/kg per d for PGF-M.) Urine flow was significantly higher during dexamethasone administration (control, 159±24; dexamethasone, 305±29 ml/24 h; P < 0.01). However, no correlation could be detected between

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Prostaglandin Production by Macrophages and the Effect of Anti‐inflammatory Drugs

Cited by 86 publications

References 48 publications

Monocytes regulate osteoclast-activating factor production by releasing prostaglandins.

Monocytes regulate osteoclast-activating factor production by releasing prostaglandins.

Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets

Effect of dexamethasone on in vivo prostanoid production in the rabbit.

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