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At least 865 records · Page 48Linked to original sources
PubMed1984

C-6-sulfidopeptide leukotrienes are unlikely to be involved in the endothelium dependent relaxation of rabbit aorta by acetylcholine.

Acetylcholine (ACh) induced dilation of precontracted strips of rabbit aorta by a mechanism dependent on an intact endothelium, probably by releasing an unknown endothelial relaxing factor (ERF). The relaxation was completely inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid (10(-5) M) but not by the cyclooxygenase inhibitor indomethacin (10(-5) M). The aortic strips were found to release small amounts of a material with a leukotriene-like activity. Its action on the guinea pig ileum was antagonized by FPL 55712 (10(-6) M). However, FPL 55712 (10(-6) - 10(-4) M) did not alter the response of rabbit aortic strips to ACh. Also when decreasing intracellular concentrations of glutathion (GSH) by incubating the strips with diethylmaleat or 2-cyclohexen-1-one (both 10(-3) M) the vasodilator response could still be elicited. Leukotriene (LT) C4 and LTD4 (10(-9) - 10(-6) M) were found to be ineffective on aortic strips under basal or induced tension. The same held true for LTE4 (10(-9) - 10(-7) M). At 10(-6) M, however, LTE4 induced slight relaxations of the vascular tissues. For reasons discussed this is likely to be a pharmacological action independent of the effects of endogenous ERF (e.g. inhibition of the formation of the LTE4 precursor LTD4 by high extracellular GSH concentrations did not reverse the ACh-induced vasodilation). It is concluded from these data, that C-6-sulfidopeptide leukotrienes, although probably produced by vascular tissue, are unlikely to be involved in the ACh-induced relaxation of rabbit aorta.

Acetylcholine↗
PubMed1992

Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase.

Liver transplantation is the only effective treatment for hereditary tyrosinaemia type I (McKusick 276700). We have treated one acute and four subacute-chronic cases with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27), to prevent the formation of maleylacetoacetate and fumarylacetoacetate and their saturated derivatives. The oral daily dose was 0.1-0.6 mg/kg. The excretion of succinylacetoacetate and succinylacetone decreased from 15-103 mmol/mol creatinine to the detection limit or slightly above (ie, to 20-150 mumol/mol creatinine). The concentration of succinylacetone in plasma decreased from 5.8-43 mumol/l to the detection limit (0.1 mumol/l) over 2-5 months of treatment. The almost complete inhibition of porphobilinogen synthase in erythrocytes was abolished and the excretion of 5-aminolevulinate decreased to within or slightly above the reference range. The concentration of alpha-fetoprotein decreased in four patients to 1.3-7.5% of initially high values over 6-8 months. Improved liver function was reflected by normal concentrations of prothrombin complex and in decreased activities of alkaline phosphatase and gamma-glutamyltransferase in serum. Computed tomography revealed regression of hepatic abnormalities in three patients. One patient developed rickets 6 months before treatment and had excreted high concentrations of markers of tubular dysfunction--after 3 weeks of treatment, this excretion had disappeared. No side-effects were encountered. Inhibition of 4-hydroxyphenylpyruvate dioxygenase may prevent the development of liver cirrhosis and abolish or diminish the risk of liver cancer. Normalisation of porphyrin synthesis will eliminate the risk of porphyric crises. This type of treatment may thus offer an alternative to liver transplantation in hereditary tyrosinaemia.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1996

Chemical modification of the arginyl residue in silk fibroin: 2. Reaction of 1,2-cyclohexanedione in aqueous alkaline medium.

The arginyl residue of solubilized silk fibroin was chemically modified with 1,2-cyclohexanedione in aqueous alkaline medium to form a stable imidazolidinone ring, and its positive charge was masked. CD spectra of the modified silk fibroin in aqueous solution showed an increase in the fraction of random coil conformation. The increase may be caused by the exposure to alkaline medium in the modification reaction. FT-IR and CD spectra of the silk fibroin films before and after the modification indicated that the conformational change in the modified silk fibroin in the solid state did not occur by the modification of its arginyl residue with 1,2-cyclohexanedione. The chemical stability of the modified silk fibroin film was investigated in vitro with phosphate-buffered saline solution. The modified arginyl residue in the film was stable in the phosphate-buffered solution.

Animals↗
PubMed1990

The antigenic structure of HBsAg: study of the d/y subtype determinant by chemical modification and site directed mutagenesis.

Lysine residue 122 of the major protein of HBsAg/adw has been shown previously to be involved in the d subtype determinant. We demonstrate here that the corresponding residue of the HBsAg/ayw, arginine 122, does not play such a critical role the y site of this antigen subtype. Thus, conversion by site directed mutagenesis of arginine 122 to lysine 122 in HBsAg/ayw does not result in the loss of y activity nor gain of d activity. Moreover, chemical modification studies of both the adw and ayw antigens with the reagents o-methylisourea and cyclohexanedione, demonstrate that arginine 122 plays at most only a minor role in this subtype antigenic site.

Antibodies, Monoclonal↗
PubMed1983

Heme models of peroxidase enzymes: deuteroferriheme-catalyzed chlorination of monochlorodimedone by sodium chlorite.

The iron(III) complex of deuteroporphyrin(IX), deuteroferriheme, catalyzes the chlorination, by sodium chlorite, of the active methylene compound monochlorodimedone (MCD) to dichlorodimedone. Rate studies, carried out on a stopped-flow spectrophotometric time scale, show the chlorination to be zero-order in MCD, first-order in ClO2- and to display a complex dependence on heme. The active chlorinating agent is believed to be hypochlorite, OCl-, formed as a result of the initial two-electron oxidation of heme to peroxidatic intermediate by chlorite ion. This scheme is supported by the fact that the normal (4:1) heme:ClO2- molar stoichiometry is reduced in the presence of MCD to values approaching 2:1. This suggests that MCD is an effective scavenger of OCl-, which, in the absence of active methylene compound, serves as a two-electron oxidant of heme. The zero-order dependence of rate on MCD is attributed to the slow formation of OCl-, consequent to a mechanism in which the rate-limiting step is viewed to be the regeneration of free heme from peroxidatic intermediate, probably via a catalatic pathway. Support for such a mechanism is provided by the fact that addition of ascorbate greatly enhances the rate of MCD chlorination, presumably by accelerating the rate of heme regeneration via perioxidation reduction of the heme intermediate.

Chlorides↗
PubMed1988

Mutagenicity studies on ketone solvents: methyl ethyl ketone, methyl isobutyl ketone, and isophorone.

3 ketone solvents (methyl ethyl ketone (MEK), methyl isobutyl ketone (MiBK), and isophorone) were tested for potential genotoxicity. The assays of MEK and MiBK included the Salmonella/microsome (Ames) assay, L5178Y/TK+/- mouse lymphoma (ML) assay, BALB/3T3 cell transformation (CT) assay, unscheduled DNA synthesis (UDS) assay, and micronucleus (MN) assay. Only the ML, UDS, and MN assays were conducted on samples of isophorone. No genotoxicity was found for MEK or isophorone. The presence of a marginal response only at the highest, cytotoxic concentration tested in the ML assay, the lack of reproducibility in the CT assay, and clearly negative results in the Ames assay, UDS and MN assays, suggest that MiBK is unlikely to be genotoxic in mammalian systems.

Animals↗
PubMed1987

Prolonged odor exposure causes severe cell shrinkage in the adult rat olfactory bulb.

Adult sensory systems generally remain viable as long as stimulation or disease do not physically damage the sensors. Continuous exposure of adult rats to a single odor for two months, however, caused a shrinkage of mitral cells in the olfactory bulb which was more extensive and severe than found in adult rats exposed to deodorized air, or normal rat colony odors. The results suggest that lack of excitation of mitral cells may cause significant shrinkage (deodorized air treatment), but more severe shrinkage may occur through inhibition or masking by a single dominant odor in the environment. These results have implications for humans living or working in odorous environments.

Animals↗
PubMed1983

Modification of arginines in D-beta-hydroxybutyrate dehydrogenase.

D-beta-Hydroxybutyrate dehydrogenase (D-3-hydroxybutyrate: NAD+ oxidoreductase, EC 1.1.1.30) is a lipid-dependent enzyme which has an absolute and specific requirement for phosphatidylcholine for function. Chemical derivatization studies using 1,2-cyclohexanedione, an arginine-specific reagent, have been carried out on the purified enzyme devoid of lipid as well as on the enzyme reactivated with phospholipid. Cyclohexanedione inactivated the active enzyme-phospholipid complex and the lipid-free enzyme was rendered inactivatable by phospholipid. From kinetic studies and by direct chemical derivatization studies with [1-14C]cyclohexanedione, we find that incorporation of a single cyclohexanedione molecule per enzyme monomer resulted in complete loss of enzymic activity. The presence of NADH or NAD+, cofactors for the enzyme, offered no protection for the rate of inactivation. The substrates beta-hydroxybutyrate and acetoacetate with or without coenzyme gave little or no protection. However, 2-methyl malonate, a competitive inhibitor for beta-hydroxybutyrate, strongly protected against inactivation. These studies indicate that: (1) a single arginine serves a vital role and is essential for function; (2) the arginine is located in the proximity of the substrate binding site.

Animals↗
PubMed1987

Inhibition of staphylococcal alpha-toxin by covalent modification of an arginine residue.

The effects of 1,2-cyclohexanedione and phenylglyoxal on staphylococcal alpha-toxin were studied. Modification of one arginine residue in alpha-toxin was sufficient to render the toxin nonhemolytic with no conformational change. Modified alpha-toxin did not protect cells from hemolysis by native alpha-toxin. An arginine residue is therefore at or near the binding site of alpha-toxin. Trypsin digestion of modified alpha-toxin generated a 20 kDa fragment which was isolated using a boric acid gel column. Upon regeneration, this 20 kDa fragment was not recognized by a population of antibodies which prevented alpha-toxin binding. The fragment was recognized by antibodies directed against post-binding events. However, the antibinding antibodies recognized the intact modified toxin. This leads us to conclude that antibinding determinants are not found directly in the binding site or are conformationally masked.

Animals↗
PubMed1988

The mechanism of myeloperoxidase-dependent chlorination of monochlorodimedon.

Chlorination of monochlorodimedon is routinely used to measure the production of hypochlorous acid catalysed by myeloperoxidase from H2O2 and Cl-. We have found that the myeloperoxidase/H2O2/Cl- system, at pH 7.8, catalysed the loss of monochlorodimedon with a rapid burst phase followed by a much slower steady-state phase. The loss of monochlorodimedon in the absence of Cl- was only 10% of the steady-state rate in the presence of Cl-, which indicates that the major reaction of monochlorodimedon was with hypochlorous acid. During the steady-state reaction, myeloperoxidase was present as 100% compound II, which cannot participate directly in hypochlorous acid formation. Monochlorodimedon was necessary for formation of compound II, since it was not formed in the presence of methionine. Both the amount of hypochlorous acid formed during the burst phase, and the steady-state rate of hypochlorous acid production, increased with increasing concentrations of myeloperoxidase and with decreasing concentrations of monochlorodimedon. Inhibition by monochlorodimedon was competitive with Cl-. From these results, and the ability of myeloperoxidase to slowly peroxidase monochlorodimedon in the absence of Cl-, we propose that the reaction of monochlorodimedon with the myeloperoxidase/H2O2/Cl- system involves a major pathway due to hypochlorous acid-dependent chlorination and a minor peroxidative pathway. Only a small fraction of compound I needs to react with monochlorodimedon instead of Cl- at each enzyme cycle, for compound II to rapidly accumulate. Monochlorodimedon, therefore, cannot be regarded as an inert detector of hypochlorous acid production by myeloperoxidase, but acts to limit the chlorinating activity of the enzyme. In the presence of reducing species that act like monochlorodimedon, the activity of myeloperoxidase would depend on the rate of turnover of compound II. Components of human serum promoted the conversion of ferric-myeloperoxidase to compound II in the presence of H2O2. We suggest, therefore, that in vivo the rate of turnover of compound II may determine the rate of myeloperoxidase-dependent production of hypochlorous acid by stimulated neutrophils.

Chlorides↗
PubMed1989

Protection of hexaprenyl-diphosphate synthase of Micrococcus luteus B-P 26 against inactivation by sulphydryl reagents and arginine-specific reagents.

Hexaprenyl-diphosphate synthase from Micrococcus luteus B-P 26 has been shown to comprise two essential components, designated as components A and B. Treatment of the synthase with sulphydryl reagents (N-ethylmaleimide, iodoacetamide or p-chloromercuribenzoate) or arginine-specific reagents (2,3-butanedione, 1,2-cyclohexanedione or phenylglyoxal) resulted in a rapid loss of the component B activity. In contrast, component A was resistant to treatment with such reagents, retaining the initial activity almost completely. Farnesyl diphosphate, isopentenyl diphosphate, farnesyl monophosphate and inorganic pyrophosphate protected the synthase against the inactivation by N-ethylmaleimide, farnesyl diphosphate being the most effective. The presence of Mg2+ was essential for the protection by isopentenyl diphosphate and inorganic pyrophosphate. For protection of the synthase activity against the inactivation by 2,3-butanedione, the presence of farnesyl diphosphate, isopentenyl diphosphate and Mg2+ was more effective than that of the individual substrates and Mg2+. Inorganic pyrophosphate provided substantial protection. In the absence of component A, the component B activity was not protected by any substrates or its analogue. These results suggest that the catalytic site of the synthase is formed by cooperative interaction between components A and B, and that cysteine and arginine residues on component B play important roles in the synthase activity.

Aldehydes↗
PubMed1990

The chlorinating activity of human myeloperoxidase: high initial activity at neutral pH value and activation by electron donors.

The steady-state activity of myeloperoxidase in the chlorination of monochlorodimedone at neutral pH was investigated. Using a stopped-flow spectrophotometer we were able to show that the enzymic activity at pH 7.2 rapidly declined in time. During the first 50-100 ms after addition of H2O2 to the enzyme, a turnover number of about 320 s-1 per haem was observed. However, this activity decreased rapidly to a value of about 25s-1 after 1 s. This shows that in classical steady-state activity measurements, the real activity of the enzyme at neutral pH is grossly underestimated. By following the transient spectra of myeloperoxidase during turnover it was shown that the decrease in activity was probably caused by the formation of an enzymically inactive form of the enzyme, Compound II. As demonstrated before (Bolscher, B.G.J.M., Zoutberg, G.R., Cuperus, R.A. and Wever, R. (1984) Biochim. Biophys. Acta 784, 189-191) reductants such as ascorbic acid and ferrocyanide convert Compound II, which accumulates during turnover, into active myeloperoxidase. Activity measurements in the presence of ascorbic acid showed, indeed, that the moderate enzymic activity was higher than in the absence of ascorbic acid. With 5-aminosalicylic acid present, however, the myeloperoxidase activity remained at a much higher level, namely about 150 s-1 per haem during the time interval from 100 ms to 5 s after mixing. From combined stopped-flow/rapid-scan experiments during turnover it became clear that in the presence of 5-aminosalicylic acid the initially formed Compound II was rapidly converted back to native enzyme. Presteady-state experiments showed that 5-aminosalicylic acid reacted with Compound II with a K2 of 3.2 x 10(5) M-1.s-1, whereas for ascorbic acid a K2 of 1.5 x 10(4) M-1.s-1 was measured at pH 7.2. In the presence of 5-aminosalicylic acid during the time interval in which the myeloperoxidase activity remained constant, a Km for H2O2 at pH 7.2 was determined of about 30 microM at 200 mM chloride. In the absence of reductants the same value was found during the first 100 ms after addition of H2O2 to the enzyme. The physiological consequences of these findings are discussed.

Aminosalicylic Acids↗
PubMed1985

Reversal of antisecretory activity of omeprazole by sulfhydryl compounds in isolated rabbit gastric glands.

We have examined the interaction of omeprazole, a gastric antisecretory agent, with endogenous or exogenous sulfhydryl compounds in isolated rabbit gastric glands. The glands exposed to omeprazole (2 microM for 50 min) could recover acid secretory response to dibutyryl-cAMP upon addition of dithiothreitol, cysteine or glutathione. Washing the omeprazole-exposed glands free of the extracellular drug also led to a similar recovery of the acid secretory response. Depletion of cellular glutathione with 2-cyclohexen-1-one had no considerable effect on the secretory response of the glands to dibutyryl-cAMP, but prevented the reversal of the antisecretory effect of omeprazole upon washing or adding exogenous cysteine. Also, the antisecretory potency of omeprazole increased several fold in the glutathione-depleted glands. These observations indicate that cellular glutathione is essential to reactivate the omeprazole-modified enzyme(s), possibly (H+ + K+)-ATPase, in acid secretory process and led us to propose that omeprazole is an agent reacting with sulfhydryl groups.

Animals↗
PubMed1991

Tumor necrosis factor-alpha stimulates phosphatidylinositol breakdown by phospholipase C to coordinately increase the levels of diacylglycerol, free arachidonic acid and prostaglandins in an osteoblast (MC3T3-E1) cell line.

The effects of (human recombinant) tumor necrosis factor-alpha on phosphatidylinositol breakdown, release of 1,2-diacylglycerols, mobilization of arachidonate from diacylglycerol and prostaglandin synthesis were examined in a model osteoblast cell line (MC3T3-E1). Tumor necrosis factor-alpha (10 nM) caused a specific (30%) decrease in the mass of phosphatidylinositol (and no other phospholipids) within 30 min of exposure. Tumor necrosis factor-alpha doubled the rate of incorporation of [32P]orthophosphoric acid into phosphatidylinositol, indicating that the turnover of inositol phosphate was enhanced, and increased the content of diacylglycerol in parallel with phosphatidylinositol breakdown. The cytokine (10-50 nM; 4 h) also promoted a specific release of 24-34% of the [3H]arachidonate from prelabeled phosphatidylinositol, a release of 80% of the 3H-fatty acid from the diacylglycerol pool, and a 30-fold increase in the synthesis of prostaglandin E2. The tumor necrosis factor-alpha induced liberation of [3H]arachidonate from diacylglycerol, cellular arachidonate release and the synthesis of prostaglandin E2 were each blocked by an inhibitor of diacylglycerol lipase, the compound RHC 80267 (30 microM). Therefore, we conclude that, in the MC3T3-E1 cell line, tumor necrosis factor-alpha activates a phosphatidylinositol-specific phospholipase C (phosphatidylinositol inositolphosphohydrolase; EC 3.1.4.3) to release diacylglycerol, and increases the metabolism of diacylglycerol to liberate arachidonate for prostaglandin synthesis.

Animals↗
PubMed1992

Pathways for arachidonic acid mobilization in zymosan-stimulated mouse peritoneal macrophages.

Resident peritoneal macrophages release arachidonic acid when challenged by zymosan, a phagocytosable particle. The present study was designed to investigate the pathways for arachidonic acid mobilization in zymosan-stimulated macrophages. Experiments were conducted with [3H]arachidonic acid-labeled macrophages to establish the relative contribution of acyltransferases, phospholipase A2, and diacylglycerol lipase to overall arachidonic acid release. Upon zymosan stimulation, [3H]arachidonic acid incorporation into phospholipids was significantly enhanced. Stimulus-induced activation of arachidonic acid incorporated was not observed immediately, but was found 5 min after cell challenge. On the other hand, the results indicated a rapid accumulation of intracellular free [3H]arachidonic acid that paralleled the appearance of both [3H]glycerol-labeled lysophosphatidylcholine and [3H]glycerol-labeled lysophosphatidylinositol, the by-products of phospholipase A2 action on phosphatidylcholine and phosphatidylinositol, respectively. A transient accumulation of [3H]arachidonate-carrying diacylglycerol was also observed. However, no appreciable alterations in the levels of [3H]monoacylglycerol were found. The phospholipase A2 inhibitor nordihydroguaiaretic acid substantially prevented the zymosan-induced arachidonic acid release. In contrast, RHC 80267, a diacylglycerol lipase inhibitor, though preventing diacylglycerol breakdown, did not have any effect on [3H]arachidonic acid release From these results, it is concluded that: (1) the phospholipase A2 pathway controls arachidonic acid release upon zymosan stimulation; (2) the diacylglycerol lipase pathway appears not to be involved in arachidonic acid release by stimulated cells; (3) the acyltransferases play a remarkable role in controlling free arachidonic acid levels, but they do not participate in the increase of free fatty acid levels observed upon cell stimulation.

Acyltransferases↗
PubMed1985

Inhibition of lectin-induced lymphocyte activation by 2-cyclohexene-1-one: analysis of DNA synthesis in individual cells by BUdR quenching of Hoechst 33258.

A novel technique utilizing the quenching of fluorescence Hoechst 32258 by bromodeoxyuridine (BUdR) was used to investigate the effect of depressed glutathione (GSH) on the activation of human peripheral blood lymphocytes by phytohemagglutinin (PHA) or concanavalin A (con A). This technique allows the quantification of DNA synthesis in individual cells. Lymphocytes were purified by Ficoll-Hypaque density gradient centrifugation and treated with 5 X 10(-5) M to 1 X 10(-6) M 2-cyclohexene-1-one (2-CHX-1), a reagent which specifically depletes intracellular GSH, and/or interferes with GSH-protein interactions, and 25 micrograms/ml BUdR in the presence or absence of PHA or con A. At 72 h lymphocyte smears were stained with Hoechst 33258 and examined using a computer controlled microscope photometer. When DNA synthesis was assayed using BUdR quenching two populations of lymphocytes were noted; a population which incorporated little or no BUdR (unactivated) and a population which incorporated BUdR sufficient to quench 33258 fluorescence by approximately 35%. Cells treated with graded doses of 2-CHX-1 which reduced glutathione levels by 10-90%, showed a progressive loss of cells from the activated population and the appearance of these cells in the inactivated population. Statistical analysis of the frequency histograms demonstrated that there were no cells which incorporated an intermediate amount of BUdR. This data demonstrates that depressed intracellular GSH or inhibition of GSH-protein interactions inhibits an early step in the biochemical sequence of events leading to DNA synthesis but does not inhibit the DNA synthetic process per se.

Benzimidazoles↗
PubMed1991

The role of glutathione in lymphocyte activation--II. Effects of buthionine sulfoximine and 2-cyclohexene-1-one on early and late activation events.

Depletion of intracellular glutathione (GSH) inhibits the lectin-induced activation response of human T lymphocytes. GSH-depleted lymphocytes undergo a partial activation response to lectins but fail to undergo blast transformation. Several lines of evidence indicate that the inhibition of lymphocyte activation in GSH-depleted lymphocytes involves relatively late activation events. Firstly, lectin stimulation induces significant 14C-AIB uptake, IL-2 production and expression of IL-2 receptor but a near complete inhibition of 3H-uridine and 3H-thymidine incorporation. Comparable levels of IL-2 production and IL-2 receptor expression are seen in GSH-depleted lymphocytes allowed to recover from GSH depletion during lectin stimulation. However, in the latter case, 3H-uridine and 3H-thymidine incorporation are normal, and activation is completely restored. Exogenous IL-2 cannot restore activation in GSH-depleted lymphocytes. Furthermore, lymphocytes remain highly susceptible to inhibition by GSH depletion even after 48 h of lectin stimulation which is sufficient to induce early activation events in the Go----G1 transition, such as IL-2 receptor expression and IL-2 production. Exogenous GSH partially restores intracellular GSH levels and completely restores lymphocyte activation in GSH-depleted lymphocytes. Despite comparable degrees of GSH depletion, DL-buthionine-SR-sulfoximine and 2-cyclohexene-1-one inhibit lymphocyte activation to different degrees. The inhibition by 2-cyclohexene-1-one is consistently greater than would be predicted based on glutathione depletion per se. We conclude that GSH-dependent processes are important in relatively late steps of the activation sequence characterized by nuclear events with relative sparing of essential early steps in activation, such as IL-2 receptor expression and IL-2 production. The approximate minimal intracellular GSH concentration necessary to sustain a normal activation response is 2 nmol per 10(7) lymphocytes.

Aminoisobutyric Acids↗
PubMed1992

Potentiation by thiopurines and sulfhydryl-reactive agents of the inhibition by 3-deazaadenosine of mononuclear phagocytes.

Combination effects of 3-deazaadenosine (c3Ado) on antibody-dependent phagocytosis in mouse resident peritoneal cells and human peripheral blood monocytes precultured with cytotoxic thiols, azathioprine (AZA) or 6-mercaptopurine (6-MP), and thiol-reactive agents, 2-cyclohexene-1-one (2-CH) or ethacrynic acid (ETA), are described. In the mouse cell preparations, a non-inhibitory concentration of 10 microM AZA or 6-MP potentiated the inhibition by 5 and 10 microM c3Ado of phagocytosis. Higher concentrations of AZA or 6-MP (50, 100 microM) and c3Ado (40, 50 microM) were needed to achieve similar effects in human monocytes. Both 2-CH (50 microM) and ETA (25 microM) inhibited mouse cell phagocytosis and acted synergistically with c3Ado. Precultivation of mouse cells with an inhibitor of glutathione synthesis, buthionine sulfoximine (BSO, 50 microM) caused no inhibition of phagocytosis and no potentiation of the inhibition by c3Ado, although BSO potentiated the inhibition by 2-CH (50 microM). In human monocytes, non-inhibitory concentrations (10 and 25 microM) of gold sodium thiomalate (GST), AZA, and c3Ado, but not 6-MP, potentiated the inhibition by 2-CH (25-37.5 microM) of phagocytosis. Results are discussed in connection with the possible modulation by endogenous sulfhydryl-reactive metabolites of phospholipid turnover of the effects of c3Ado.

Animals↗