Prostaglandin biosynthetic capacity of hepatomas with different growth rates

1. Prostaglandin synthesis from [14C]arachidonate by microsomal fractions was measured with preparations from rat liver and from hepatomas of different growth rates. The highest rates of synthesis were observed with microsomal preparations from the rapidly growing hepatoma HTC. 2. Assay of endogenous levels of prostaglandins E2, F2 alpha and thromboxane B2 also indicated high levels in solid tumors of the HTC line. 3. With HTC cells in culture it was necessary to incubate in the absence of serum in order to detect prostaglandin synthesis. 4. The data indicated that, while prostaglandin synthesis was elevated in HTC cells, the synthesis of prostaglandins by a series of hepatomas was not closely correlated with the growth rates of the tumors.     

Effect of eicosanoids on the accumulation of cholesterol and the proliferation of subendothelial cells in the human aorta

The effect of prostacyclin and stable thromboxane analog A2 on endothelial culture of human aorta was studied. It was shown that prostacyclin inhibited accumulation of cholesterol in the cells and their proliferation, while thromboxane exhibited an opposite effect. Calcium antagonists potentiated effects of prostacyclin and inhibited them in respect to thromboxane. Screening of a number of synthetic agents affecting arachidonic acid metabolism was carried out. It was found that lipoxygenase inhibitors suppress cholesterol accumulation and proliferation in cells presumably due to enhancement of prostacyclin synthesis and inhibition of leukotriene formation. The balance between various eicosanoids is supposed to be an important factor of atherogenesis regulation, while antiatherogenic effect of calcium antagonists is somehow associated with the impact of eicosanoids on atherogenesis regulation.     

Role of contaminating platelets in thromboxane synthesis in primary cultures of human umbilical vein endothelial cells

Previous studies suggested that cultured human endothelial cells metabolize arachidonic acid to thromboxane A2. When primary cultures of human umbilical vein endothelial cells were incubated with 14C-arachidonic acid and the 14C-metabolites resolved by reverse phase high pressure liquid chromatography, radioactive products were observed that comigrated with 6-keto-prostaglandin F1alpha and thromboxane B2, the degradation products of prostacyclin and thromboxane A2, respectively. Since platelets synthesize thromboxane A2, the present study examined the hypothesis that adherent platelets may contaminate the primary cultures of human umbilical vein endothelial cells and be responsible for thromboxane B2 production. Confluent primary cultures or passaged cells were stimulated with histamine (10(-5) M). Incubation buffer was analyzed by specific radioimmunoassays for 6-keto-prostaglandin F1alpha and thromboxane B2. The production of thromboxane B2 decreased in the passaged cells (207 +/- 44 pg/ml versus 65 +/- 12 pg/ml; primary versus passaged cells). A moderate decrease in the yield of 6-keto-prostaglandin F1alpha was measured in the passaged cells compared to the primary cultures (3159 +/- 356 pg/ml versus 1678 +/- 224 pg/ml, primary versus passaged cells). If the primary cultures were incubated with human platelet-rich plasma for 30 min prior to stimulation with histamine, the amount of thromboxane B2 increased approximately 10-fold. In an additional experiment, sub-confluent primary cells were incubated with platelet-rich plasma for 30 min, washed to remove non-adherent platelets, and allowed to reach confluency. Confluent cells were then passaged and stimulated with histamine. The amount of thromboxane B2 was not significantly different from that obtained with passaged cells that had not been incubated with platelet-rich plasma during the primary culture (83 +/- 15 pg/ml versus 65 +/- 12 pg/ml, respectively). If the cyclooxygenase inhibitor indomethacin was included in the incubations, the amounts of both thromboxane B2 and 6-keto-prostaglandin F1alpha decreased. In contrast, the thromboxane A2 synthase inhibitor dazoxiben blocked thromboxane production and had no effect on the amount of 6-keto-prostaglandin F1alpha. Light microscopy revealed the presence of adherent platelets in primary cultures with and without platelet-rich plasma but no platelets were observed in any group of passaged cells. Histofluorescence for platelet serotonin indicated the presence of platelets only in primary cultures of human umbilical vein endothelial cells or in cultures pre-incubated with platelet-rich plasma. These studies suggest that primary cultures of human umbilical vein endothelial cells contain adherent platelets that contribute to thromboxane synthesis.     

Does thromboxane mediate the indirect contractile action of leukotriene D4 in guinea-pig isolated lung parenchyma under equilibrium conditions?

The role that thromboxane A2 plays in contractions induced by leukotriene D4 in guinea-pig isolated lung parenchyma was investigated under equilibrium conditions. Lung tissue generated thromboxane A2 and prostacyclin spontaneously as evidenced by the slow accumulation of their biologically inactive metabolites, thromboxane B2 and 6-keto-prostaglandin F1 alpha, in the bathing buffer. Challenge of guinea-pig lung parenchyma with a high concentration (EC90 for tension generation) of leukotriene D4 (200 nM) produced a biphasic contraction of the tissue that consisted of an initial rapid increase in isometric tension followed by a slowly developing, well-sustained contracture. In addition, leukotriene D4 (200 nM) effected a transient increase (over basal) in the generation of thromboxane A2 and prostacyclin that lagged significantly behind the tension response. Kinetic analysis of the mechanical and eicosanoid-generating effect of leukotriene D4 revealed that tension development could be suitably fitted to a biexponential function, whilst the release of both eicosanoids from the lung occurred monoexponentially. Pretreatment of the lung with the cyclooxygenase inhibitor, flurbiprofen, which effectively abolished both the spontaneous and the leukotriene D4-stimulated eicosanoid biosynthesis, significantly reduced both the first order rate coefficient of the first exponent and the maximum amplitude of this function with respect to control. This change in the kinetics describing leukotriene D4-induced contractions was explained by the fact that the initial rate of tension development was markedly reduced following pretreatment of the lung with flurbiprofen. Neither the inhibitor of thromboxane synthetase, dazmegrel, which selectively inhibited (by 95%) leukotriene D4-stimulated thromboxane A2 formation, nor blockade of 11 alpha,9 alpha-epoxymethano-prostaglandin H2 (U-46619)-sensitive (thromboxane A2) receptors with either AH 23848 or EP 092 affected the profile of leukotriene D4-induced tension development in guinea-pig lung. It is concluded that a high concentration of leukotriene D4 (200 nM) contracts guinea-pig lung by both a direct and indirect mechanism. Initially, a rapid short-lived contraction of the lung is manifest which is dependent, in part, upon the synthesis and release of cyclooxygenase product(s) other than thromboxane A2. This initial response occurs coincidently with, and is subsequently followed by, the development of a tonic well-sustained contracture that is the result of a direct action of leukotriene D4 on the contractile cells that comprise the lung.     

Macrophage eicosanoid formation is stimulated by platelet arachidonic acid and prostaglandin endoperoxide transfer

The present study was designed to determine whether platelets transfer arachidonic acid or prostaglandin endoperoxide intermediates to macrophages which may be further metabolized into cyclooxygenase products. Adherent peritoneal macrophages were prepared from rats fed either a control diet or an essential fatty acid-deficient diet, and incubated with a suspension of washed rat platelets. Macrophage cyclooxygenase metabolism was inhibited by aspirin. In the presence of a thromboxane synthetase inhibitor, 7-(1-imidazolyl)heptanoic acid, immunoreactive 6-ketoprostaglandin F1 alpha formation was significantly increased 3-fold. Since this increase was greater (P less than 0.01) than that seen with either 7-(1-imidazolyl)heptanoic acid-treated platelets or aspirin-treated macrophages alone, these results indicate that shunting of endoperoxide from platelets to macrophages may have occurred. In further experiments, macrophages from essential fatty acid-deficient rats were substituted for normal macrophages. Essential fatty acid-deficient macrophages, depleted of arachidonic acid, produced only 2% of the amount of eicosanoids compared to macrophages from control rats. When platelets were exposed to aspirin, stimulated with thrombin, and added to essential fatty acid-deficient macrophages, significantly more immunoreactive 6-ketoprostaglandin F1 alpha was formed than in the absence of platelets. This increased macrophage immunoreactive 6-ketoprostaglandin F1 alpha synthesis, therefore, must have occurred from platelet-derived arachidonic acid. These data indicate that in vitro, in the presence of an inhibition of thromboxane synthetase, prostaglandin endoperoxides, as well as arachidonic acid, may be transferred between these two cell types.     

Regulatory effects of eicosanoids on thymidine uptake by vascular smooth muscle cells of rats

To define the roles of eicosanoids in vascular smooth muscle cells (VSMC) growth, we examined the effects of exogenous eicosanoids on (3H)thymidine uptake by cultured VSMC of Wistar rats. Stable prostacyclin (PGI2) analog, OP-41483, significantly decreased the incorporation of (3H)thymidine into deoxyribonucleic acid (DNA) of VSMC in a dose dependent manner from 10(-8) to 10(-4) M. Prostaglandin E2 (PGE2) and PGD2 ranging from 10(-8) to 10(-4) M also dose-dependently decreased the (3H)thymidine uptake by VSMC. In contrast, stable thromboxane A2 analog, STA2, significantly increased the incorporation of (3H)thymidine into DNA in a dose dependent manner from 10(-8) to 10(-4) M. The dose response curve of STA2 was shifted toward a lowered response when 10(-5) M PGI2 analog, PGE2 or PGD2 was added in the culture medium. Thus, it is indicated that vasodepressor eicosanoids decrease the proliferation of VSMC, whereas vasoconstrictor TXA2 enhances the VSMC growth. Vascular smooth muscle cells possibly autoregulate the cell proliferation through the eicosanoids generation.     

Testing the "redirection hypothesis" of prostaglandin metabolism in the kidney

Furosemide increases the synthesis of two major renal eicosanoids, prostacyclin (PGI2) and thromboxane A2 (TXA2), by stimulating the release of arachidonic acid which in turn is metabolized to PGG2/PGH2, then to PGI2 and TXA2. PGI2 may mediate, in part, the early increment in plasma renin activity (PRA) after furosemide. We hypothesized that thromboxane synthetase inhibition should direct prostaglandin endoperoxide metabolism toward PGI2, thereby enhancing the effects of furosemide on renin release. Furosemide (2.0 mg . kg-1 i.v.) was injected into Sprague-Dawley rats pretreated either with vehicle or with U-63,557A (a thromboxane synthetase inhibitor, 2 mg/kg-1 followed by 2 mg/kg-1 X hr-1). Urinary 6ketoPGF1 alpha and thromboxane B2 (TXB2), reflecting renal synthesis of PGI2 and TXA2, as well as PRA and serum TXB2, were measured. Serum TXB2 was reduced by 96% after U-63,557A. U-63,557A did not affect the basal PRA. Furosemide increased PRA in both vehicle and U63,557A treated rats. However, the PRA-increment at 10, 20 and 40 min following furosemide administration was greater in U-63,557A-treated rats than in vehicle-treated rats and urine 6ketoPGF1 alpha excretion rates were increased. These effects of thromboxane synthesis inhibition are consistent with a redirection of renal PG synthesis toward PGI2 and further suggest that such redirection can be physiologically relevant.     

Synthesis of eicosanoids by Propionibacterium acnes-elicited liver adherent cells and their effect on production of interleukin 1 and tumor necrosis factor

When heat-killed Propionibacterium acnes (P. acnes) is intravenously injected into rats or mice, liver adherent cells including macrophages and Kupffer cells increase in number and they synthesize various kinds of biologically-active materials. We studied the production of eicosanoids and the cytokines, interleukin 1 (IL-1) and tumor necrosis factor (TNF), by P. acnes-elicited liver adherent cells and the regulatory mechanisms of eicosanoids in the synthesis of cytokines. As a result, P. acnes-elicited liver adherent cells synthesized not only prostaglandin (PG) E2, 6-keto-PGF1 alpha, thromboxane B2 and leukotriene B4, but also IL-1 and TNF. In addition, PGE2 and PGI2 suppressed the production of these cytokines. These results suggested that there are auto-regulatory mechanisms in production of cytokines in the liver.     

Endotoxin-induced lung injury in rats: role of eicosanoids

We studied lung vascular injury and quantitated lung eicosanoids in rats after intraperitoneal injection of Salmonella enteritidis endotoxin. Within 40 min after endotoxin injection (20 mg/kg), lung tissue thromboxane B2 doubled, although 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) increased by 8- to 10-fold. Lung 5-hydroxyeicosatetraenoic acid and leukotriene C4 were variably increased by endotoxin. The levels of all eicosanoids returned to base line 6 h after endotoxin challenge. Lung vascular injury, as assessed by the extravascular accumulation of 125I-albumin and water in isolated perfused lungs, was observed 90 min after endotoxin injection (0.02-20 mg/kg) in vivo. Inhibition of the cyclooxygenase pathway with indomethacin and the lipoxygenase pathway with diethylcarbamazine and 2-(12-hydroxydodeca-5,10-dinyl)-3,5,6-trimethyl-1,4-benzoqui none failed to attenuate endotoxin-induced lung injury. In addition, essential fatty acid deficiency, which markedly reduced lung tissue levels of 6-keto-PGF1 alpha, thromboxane B2, and leukotriene C4, did not protect against endotoxin injury. We conclude that although lung eicosanoids are activated during endotoxemia, they do not play a crucial role in the development of acute lung vascular injury in rats.     

Comparison of the production of eicosanoids by human and rat peritoneal macrophages and rat Kupffer cells

Human and rat peritoneal macrophages and rat Kupffer cells were labelled with [1-14C] arachidonic acid and stimulated with the calcium ionophore A23187. The metabolites formed were separated by high pressure liquid chromatography (HPLC). Human peritoneal macrophages formed especially leukotriene B4, 5-hydroxy-6,8,11,14 eicosatetraenoic acid and small amounts of leukotriene C4 and thromboxane B2, 12-hydroxy-5,8,10 heptadecatrienoic acid and 6-keto-prostaglandin F1 alpha, whereas rat peritoneal macrophages mainly produced cyclooxygenase products and in particular thromboxane B2 and 12-hydroxy-5,8,10 heptadecatrienoic acid. Rat Kupffer cells synthesized mainly cyclooxygenase products such as prostaglandin F2 alpha, prostaglandin D2 and prostaglandin E2. These results indicate that the profile of eicosanoids production by macrophages is dependent both on the species and on the tissue from which the macrophage is derived.     

Effects of (2R, 5R)-6-heptyne-2,5-diamine, a potent inhibitor of L-ornithine decarboxylase, on rat hepatoma cells cultured in vitro

DL-alpha-Difluoromethylornithine (F2MeOrn), the most widely-used inhibitor of L-ornithine decarboxylase, has been a useful tool to demonstrate that polyamine biosynthesis is required to maintain maximum rates of cell proliferation. However, in most eukaryotic cell systems, F2MeOrn exerts cytostatic rather than cytotoxic effects. This may be due to the fact that this inhibitor creates only incomplete polyamine deficiency. In particular, F2MeOrn scarcely depletes intracellular spermine levels. We now demonstrate in rat hepatoma tissue culture (HTC) cells that (2R, 5R)-6-heptyne-2,5-diamine, a more potent irreversible inhibitor of L-ornithine decarboxylase than F2MeOrn, decreases the concentrations of all polyamines including spermine. In parallel with the depletion of these amines, there is a progressive decrease in the rate of cell proliferation and in cell viability. Restoration of the intracellular polyamine content, by addition to the medium of polyamines or a high concentration of L-ornithine, the substrate of L-ornithine decarboxylase, further demonstrates that the antiproliferative effects of (2R, 5R)-6-heptyne-2,5-diamine do result from polyamine deficiency. These findings support the concept that polyamines play an essential function in the cell division processes and emphasize the vital function of spermine in mammalian cells.     

Production of prostaglandin E2 and prostacyclin by thymic nurse cells in culture

To better define the thymic microenvironment, we have examined a specific population of thymic stromal cells, thymic nurse cells (TNC) for production of eicosanoids. TNC were prepared from BALB/c mice, cultured in complete medium, and culture supernatants were analyzed for the presence of various metabolites of arachidonic acid. Freshly isolated TNC produced large quantities of PGE2 and 6-keto PGF1 alpha (a stable metabolite of prostacyclin, PGI2). Both of these eicosanoids were produced continuously in culture, after an initial lag period of approximately 2 h. No significant production of the eicosanoids PGD2, thromboxane B2, or leukotrienes B4, C4/D4/E4 was seen in these cultures. Production of PGE2 and PGI2 by TNC was not stimulated by treatment with the calcium ionophore A23187, or by cell-cell interactions resulting from coculture of the TNC with free thymocytes. Eicosanoid production in these cultures was not due to production of these substances by cells likely to be present as contaminants, such as T rosettes or free thymocytes. These findings raise the possibility that PGE2 and/or PGI2 may provide signals to thymocytes at a specific developmental stage.     

Prostaglandin production by phagocytic cells of the mouse thymic reticulum in culture and its modulation by indomethacin and corticosteroids

The production of prostaglandins by phagocytic cells of the thymic reticulum in culture (P-TR) was studied by using high pressure liquid chromatography and radioimmunoassay. Radioimmunologic determinations showed that thromboxane B2 (TXB2), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1 alpha (6 keto-PGF1 alpha) were the major compounds released into the culture medium, whereas prostaglandin F2 alpha (PGF2 alpha) was only a minor component. Indomethacin and dexamethasone exerted a similar pattern of differential inhibition of the secretion of prostanoids. PGE2 and 6-keto PGF1 alpha productions were markedly decreased by these anti-inflammatory drugs, whereas those of TXB2 and PGF2 alpha were not or were only slightly affected. Experiments performed with an antiglucocorticoid compound (RU 38486) showed that the steroid-induced inhibition of prostanoid secretion is a classical receptor-mediated action. These results demonstrated that phagocytic cells of the thymic reticulum, which resemble the thymic interdigitating cells, produce several types of prostaglandins. Because it has been described that P-TR regulate thymocyte proliferation in vitro via the secretion of both interleukin 1 and PGE2, these results suggest that anti-inflammatory agents may be able to modulate the thymic microenvironment and, consequently, thymocyte proliferation.     

Inositol phospholipids are probably not the source of arachidonic acid for eicosanoid synthesis in astrocytes

In astrocyte-enriched cultures of the rat cerebral cortex the Ca2+ ionophore A23187 provoked the breakdown of inositol phospholipids, the liberation of arachidonic acid and the release of prostaglandins E2, F2 alpha, I2 and thromboxane A2. However, agonists for receptors also coupled to inositol phospholipid metabolism in these cells failed to produce an increase in the release of both arachidonic acid and eicosanoids. Results suggest that the A23187-stimulated release of arachidonic acid and eicosanoids is caused by a phospholipase A2-mediated attack on lipids other than the inositol phospholipids. Moreover, receptors linked to inositol lipid turnover are not involved in the control of eicosanoid release from astrocytes.     

The relation between thromboxane and prostaglandin synthesis in human decidua tissue: a comparison of eicosanoid synthesis in minced tissue with that in a cell-free preparation

Radiotracer studies and radioimmunoassay measurements demonstrate that minced tissues of human decidua produce chiefly thromboxane B2 (TxB2) (70% of total eicosanoids) and small amounts of prostaglandin F2 alpha (PGF2 alpha) (13%) PGD2 (8%), 6-keto-PGF1 alpha (5%) and PGE2 (4%). Inhibition of thromboxane synthesis with a specific inhibitor (OKY-1581: sodium (E)-3-[4(-3-pyridylmethyl)-phenyl]-2-methyl propenoate) increased prostaglandin formation in general, with the main product being PGF2 alpha (38%), a nonenzymic derivative of PGH2. Crude particulate fractions prepared from the same tissue synthesized two major products from [3H]arachidonate, TxB2 and 6-keto-PGF1 alpha (54 and 30%, respectively) and some PGF2 alpha and PGE2 (8-8%). However, in the presence of reduced glutathione (GSH), PGE2 became the main product (81%) (TxB2, 15%; PGF2 alpha, 2%; and 6-keto-PGF1 alpha, 2%). Half-maximal stimulation of PGE2 synthesis occurred at 46 microM GSH. The GSH concentration of tissue samples was found to be 110 +/- 30 microM. We conclude that human first trimester decidua cells possess the key enzymes of prostaglandin and thromboxane synthesis. Apparently, the production of these compounds is controlled by a specific mechanism in the tissue, which keeps PGE and prostacyclin synthesis in a reversibly suppressed state, whereas the formation of thromboxane is relatively stimulated.     

Stimulation of cytosolic free calcium and inositol phosphates by prostaglandins in cultured rat mesangial cells

We studied the effects of four products of arachidonate cyclo-oxygenation on a phospholipase C-dependent signal transduction system in cultured rat glomerular mesangial cells. PGF2 alpha, PGE2 and the thromboxane A2/endoperoxide analogue U-46619 rapidly increased cytosolic free Ca2+, measured in monolayers loaded with the fluorescent intracellular probe fura-2. Peak responses were dose-dependent and unaffected by chelation of extracellular Ca2+, indicating release from internal stores. The thromboxane A2-receptor antagonist SQ 27,427 selectively inhibited responses to U-46619. The PGI2 analogue Iloprost had no effect on cytosolic Ca2+. PGF2 alpha, PGE2 and U-46619 also stimulated accumulation of total inositol phosphates during 15 min incubations. We conclude that phospholipase C activation mediates the effects of certain eicosanoids on the glomerular mesangium.     

Bradykinin-induced release of prostacyclin and thromboxanes from bovine pulmonary artery endothelial cells. Studies with lower homologs and calcium antagonists

Bovine pulmonary artery endothelial cells, in serum-free culture medium, release small quantities of prostacyclin and thromboxane A2 (3-10 and 0.1-0.3 ng/ml; measured as immunoreactive 6-ketoprostaglandin F1 alpha and thromboxane B2, respectively). The release of these substances is stimulated by up to 20-fold during a 3 min incubation with the vasodilator, bradykinin (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9). Endothelial cells incubated with [3H]arachidonic acid for 24 h and then exposed to bradykinin for 3 min release 3H into the medium, approximately 65% of which co-chromatographs with 6-ketoprostaglandin F1 alpha and 3% with thromboxane B2. The effects of bradykinin are dose-related and are often discernible when the hormone is used at concentrations believed to occur physiologically (10 pg/ml; approximately 10 pM). Furthermore, the bradykinin molecule must be intact: none of its lower homologs affects the release of prostacyclin, thromboxane A2, or 3H unless used at concentrations (1 microM or higher) unlikely to be achieved in vivo. The release appears to involve calcium uptake and calmodulin: it is abolished by EGTA (5 mM) and inhibited by the 'slow channel' calcium antagonists, verapamil and nifedipine (10-100 microM), and by the calmodulin inhibitor, trifluoperazine (3-30 microM). Our findings suggest that bradykinin exerts some of its hormonal effects by acting on specific receptors possessed by vascular endothelial cells; receptor activation is associated with calcium transport, arachidonate mobilization, and a selective synthesis of prostacyclin, a vasodilator in its own right.     

Effects of nicotinamide and structural analogs on DNA synthesis and cellular replication of rat hepatoma cells

The effects of nicotinamide and structural analogs on DNA synthesis were studied in rat hepatoma (HTC) cells. Inhibitory effects of these compounds were observed on DNA synthesis as judged by the incorporation of [3H]-thymidine into DNA. Evidence for a marked effect on DNA integrity after preincubation with 1 mM methyl methanesulfonate was provided by a fluorometric technique with ethidium bromide. There was only a small or insignificant enhancement of this effect when hepatoma cells were incubated with nicotinamide. At concentrations of 2-20 mM, 3-aminobenzamide was observed to cause greater effects than nicotinamide on DNA synthesis and integrity and on cellular proliferation in HTC cells. Comparison of the effects of nicotinamide and 3-aminobenzamide with those of N'-methylnicotinamide suggested that some of the effects on DNA synthesis may not be mediated through inhibition of poly(ADP-ribose) synthetase. Inhibition of HTC cell proliferation was observed at a concentration of 3-aminobenzamide, 2 mM, which has been reported to be nontoxic for other cell types.     

Eicosanoids production in endometriosis

In order to investigate the production of eicosanoids in human endometrium, myometrium, leiomyoma, adenomyosis, normal ovary, non-endometrial cyst and endometrial cyst, slices of each tissue were incubated. 6-Keto-prostaglandin (PG) F1 alpha, thromboxane (TX) B2, PGF2 alpha and PGE2 concentrations in the incubation medium were measured by direct RIA. 6-Keto-PGF1 alpha production of adenomyosis was significantly higher than that of endometrium, myometrium and leiomyoma, especially in the menstrual phase. The production of eicosanoids in endometrial cyst was significantly higher than that of non-endometrial cyst and normal ovary. These results suggest that endometriosis is associated with increased eicosanoid production in vivo.     

Relationship of eicosanoids to cellular and humoral immunity factors in meningococcal infection

The dynamics of the content of thromboxane B2, 6-keto-prostaglandin F1 alpha, T- and B-lymphocytes and titers of antibodies to group polysaccharides of meningococci, groups A, B and C, have been studied in 44 patients with generalized forms of meningococcal infection. As shown in this study, in patients with the clinical course of moderate severity a decrease in the number of T-lymphocytes in the first days of infection correlates with a decrease in the concentration of thromboxane B2. In some cases the concentration of thromboxane B2 and 6-keto-prostaglandin F1 alpha has been found to correlate with the titers of antibodies to group polysaccharide of group A meningococci. The severe course of meningococcal infection is characterized by the absence of correlation between eicosanoids and the immunity factors under study.