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M Parant

Publications and source records attributed to M Parant.

At least 19 recordsLinked to original sources
PubMed1992

Indirect and selective down-regulation of serum tumor necrosis factor-alpha release by interleukin-1 beta.

A selective inhibition of LPS-induced tumor necrosis factor-alpha (TNF) response in mice was caused by an injection of recombinant human interleukin-1 (IL-1). The decrease in serum TNF level reached 70 to 80 percent of the controls receiving LPS alone when IL-1 was given simultaneously or prior to the challenge. At the same time serum IL-6 release was more elevated. Ex vivo assays have shown that macrophages from IL-1 treated animals did not respond to LPS when stimulated immediately after harvesting but recovered their normal responsiveness after being cultured for 2 hours and then washed. In vitro with or without addition of IL-1, mouse elicited macrophages responded equally to LPS in releasing TNF. In the absence of a direct and lasting effect on TNF-producing cells, the host reaction responsible for the inhibitory effect of IL-1 could be related to the overproduction of corticosterone that occurred after IL-1 injection, since it was not observed in adrenalectomized animals. Indeed the blockade of corticoid secretion by indomethacin prevented the inhibition of TNF production induced by IL-1 administration before LPS challenge. TNF administration did not result in elevation of corticosterone level and in contrast to IL-1 enhanced the TNF response to LPS injection. In vitro and ex vivo assays have shown this enhanced response to LPS was linked to a direct and prolonged effect of TNF on TNF-producing cells. Muramyl dipeptide (MDP) which was used as a known priming agent for enhanced cytokine release had a similar effect on TNF-producing cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Increased permeability to choline in simian erythrocytes after Plasmodium knowlesi infection.

The permeability of simian erythrocytes to choline was found to be considerably increased after infection by the malaria parasite, Plasmodium knowlesi. Choline entry occurs by a facilitated-diffusion system involving a carrier, which displays temperature-dependence, saturability with choline (Km = 8.5 +/- 0.7 microM) and specificity. This carrier can also be inhibited by a thiol reagent, N-ethylmaleimide, at an inactivation rate which is, in the absence of choline, the same as in normal erythrocytes. Inactivation by N-ethylmaleimide can be accelerated by external choline and prevented by decamethonium, which acts as an inhibitor of choline entry in infected cells (as with dodecyltrimethylammonium). Both ethanolamine and imidazole act as inhibitors or activators of choline entry in infected erythrocytes, depending on the relative concentrations of choline and of the competing compound (i.e. ethanolamine or imidazole). After infection, the maximum velocity reached 2.84 +/- 0.5 nmol/min per 10(10) infected cells, which is more than 10 times the Vmax. of normal erythrocytes. Impairing the biosynthesis of phosphatidylcholine de novo in Plasmodium-infected erythrocytes by various methods (glucose or ATP depletion, high ethanolamine concentrations) did not result in any alteration of choline transport (Km or Vmax.), indicating that the constant triggering and transformation of choline into phosphatidylcholine by the parasite is not directly responsible for the increase in the choline transport rate after infection. This high increase in choline transport activity is more likely related to modifications in choline carriers and/or in their environment after Plasmodium infection.

Animals↗
PubMed1991

Influence of endogenous glucocorticoid on endotoxin-induced production of circulating TNF-alpha.

Mice are quite resistant to LPS toxicity but even a small dose induced a monophasic production of circulating TNF. In BCG-treated mice challenged with LPS, the greater susceptibility was associated with the capacity of producing elevated levels of TNF in the blood. During pregnancy, after adrenalectomy, and particularly after treatment with galactosamine, smaller amounts of LPS were lethal in mice. Using adrenalectomized mice, which are less sensitive to LPS toxicity than galactosamine-treated mice, it was shown that smaller doses of LPS were effective in inducing TNF release in comparison with intact animals, and that larger concentrations of serum TNF were obtained. Pretreatment of adrenalectomized mice with MDP before LPS elicited a priming effect for an enhanced TNF production that reached levels comparable to that found in BCG-primed mice. Whatever was the yield of circulating TNF, the pattern of response was similar peaking at 1.5 to 2 h to LPS injection and returning to baseline values within 4 h. Prior administration of glucocorticoid was effective in preventing the release of serum TNF in adrenalectomized mice. The level and the kinetics of serum TNF following LPS injection were not modified in pregnant or in galactosamine-treated mice, and as in control animals glucocorticoid administration prior to LPS inhibited the TNF response.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Priming effect of muramyl peptides for induction by lipopolysaccharide of tumor necrosis factor production in mice.

Lipopolysaccharide-induced necrosis of grafted tumors was potentiated by several hydrophilic and lipophilic muramyl dipeptide (MDP) derivatives administered a few hours prior to small amounts of lipopolysaccharide (LPS) in spite of low titers of induced circulating tumor necrosis factor (TNF). However, pretreatment with MDP derivatives did increase the level of TNF in the blood of mice challenged by a greater dose of LPS. The TNF amount in 2 h postendotoxin mouse serum reached a peak when the glycopeptide had been given 6 h before the challenge, being approximately 100-fold above that obtained in unprimed mice. The cytotoxic activity in mouse serum was inhibited by rabbit antibodies raised against recombinant mouse TNF. Although there exists a toxic synergism between BCG or MDP and endotoxin, the effect of certain MDP derivatives was not related to an increased susceptibility to the toxicity of LPS.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Comparative activity of human and murine tumor necrosis factor in toxicity and anti-infectious assays in mice.

In comparative experiments, the lethal effect of rHuTNF or rMuTNF was evaluated in animals sensitized by adrenalectomy or galactosamine treatment. No clear-cut difference was observed in the effective dose irrespective of the origin of the TNF preparation in Swiss or in C3H/HeJ mice. The latter mouse substrain known to be a low responder to LPS was used in the assays to evaluate the influence of LPS contamination in TNF-induced responses. Like LPS, TNF was shown to induce abortion in pregnant mice, and the mortality rate of foetuses was almost the same in animals challenged with either rHuTNF or rMuTNF. No species preference was apparent in the protective effect of TNF against a bacterial challenge. In adult mice subsequently infected with Klebsiella pneumoniae or Listeria monocytogenes, the survival rate was comparable in groups treated with both TNF preparations. In contrast, in young mice rHuTNF and rMuTNF were ineffective against Listeria and poorly active against Klebsiella organisms, whereas a significant effect was obtained with crude mouse serum containing TNF.

Abortifacient Agents, Nonsteroidal↗
PubMed1989

Effect of muramyl peptides and tumor necrosis factor on oxidative responses of human blood phagocytes.

Adjuvant muramyl dipeptides enhanced the intracellular oxidative burst induced by phorbol myristate acetate in purified human polymorphonuclear (PMN) cells and in monocytes. A stronger priming effect was obtained when muramyl dipeptide was conjugated to a protein carrier. Recombinant human tumor necrosis factor (TNF) did not modify the level of intracellular NBT reduction in PMA-stimulated PMN, although it slightly increased the secretion of superoxide anion. In contrast, TNF enhanced the intracellular oxidative burst of monocytes even at the concentration of 10 pg/ml. In human PMN only, the combination of TNF and muramyl dipeptide induced a higher oxidative response than each stimulant alone.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Involvement of reactive oxygen metabolites in the candidacidal activity of human neutrophils stimulated by muramyl dipeptide or tumor necrosis factor.

In the presence of the adjuvant glycopeptide muramyl dipeptide (MDP), purified human PMN exhibited an enhanced capacity to kill Candida albicans cells at various cell ratios. A significant effect was obtained at 100 ng/ml MDP, and the maximum was reached at 1 micrograms/ml MDP. Recombinant human tumor necrosis factor (rHuTNF), a monokine that enhances host resistance to bacterial and fungal infections, also stimulated the candidacidal potency of PMN with a maximal effect at 10(-2) ng/ml rHuTNF. When MDP- or rHuTNF-stimulated PMN were cultured with yeast cells, the intracellular production of oxygen metabolites was enhanced. Pretreatment with inhibitors of oxidative burst demonstrated that the yeast cell killing by MDP-stimulated PMN was not affected by SOD but was inhibited by sodium azide, indicating the involvement of myeloperoxidase (MPO)-halide system in fungicidal mechanisms induced by MDP. When PMN were stimulated with rHuTNF, the killing of yeast cells was neutralized by iodoacetamide, showing that the candidacidal potency of stimulated-PMN was due to oxygen derivatives. Inhibition by sodium azide and sodium benzoate indicated that these oxygen metabolites could be derived from the MPO-halide system but also from hydroxyl radical production. Moreover, SOD partially inhibited the fungicidal potency of rHuTNF-stimulated PMN, thus indicating a possible reutilization of the released O2- anion for intracellular killing. Cytochalasin B abrogated the PMN fungicidal potency in all cases.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Production of tumor necrosis factor in nude mice by muramyl peptides associated with bacterial vaccines.

Gram-negative vaccines can elicit the production of tumor necrosis factor (TNF) in mice primed by muramyl dipeptide (MDP) or by its lipophilic derivative MDP-dipalmitoyl glycerol (MDP-GDP). In mice pretreated with MDP and particularly with MDP-GDP, Bordetella pertussis vaccine was shown to be more effective than typhoid vaccine. The time course of TNF production in the blood did not indicate any difference between the effect of MDP or of MDP-GDP. In both cases the cytotoxic activity reached maximal levels by 2 h after injection of the bacterial preparations and returned to normal values between 3 and 5 h after the challenge. In nude mice, high titers of circulating TNF were also produced by combined treatment with MDP-GDP and bacterial vaccine. Moreover, in tumor-bearing mice the association of MDP or of MDP-GDP to a bacterial vaccine induced a strong hemorrhagic necrosis, whereas each treatment alone was inactive. It was also found that mice were less sick when they were primed with MDP-GDP than with MDP, and when TNF was elicited by B. pertussis instead of lipopolysaccharide. Moreover, nude mice appeared more resistant to shock and to hemoconcentration than normal mice.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Toxic shock syndrome toxin 1 as an inducer of human tumor necrosis factors and gamma interferon.

We present evidence that toxic shock syndrome toxin 1 (TSST-1) induces the production of high levels of TNF by human blood monocytes. Enriched lymphocyte preparations incubated with the staphylococcal toxin produced significant levels of TNF-like activity that is not neutralized by anti-rHuTNF antibodies and is likely to be lymphotoxin (LT or TNF-beta). We demonstrate also that TSST-1 is a potent inducer of IFN-gamma. When lymphocyte preparations were costimulated with PMA, the TSST-1 effect was strongly potentiated and the levels of cytotoxic factors, IFN-gamma, and IL-2 present in supernatant fluids were comparable to those observed after treatment with PMA and PHA. Thus, TSST-1, which is also known as an inducer of IL-1 and IL-2, stimulates the production of endogenous mediators that could play a role in the physiopathological processes of toxic shock syndrome (TSS). The described results suggest that the discrepancies in the clinical features between TSS and endotoxin shock may be related to qualitative differences in cytokine production.

Antibodies↗
PubMed1988

Tumor necrosis factor (TNF) stimulates plasminogen activator inhibitor (PAI) production by endothelial cells and decreases blood fibrinolytic activity in the rat.

The effect of human recombinant tumor necrosis factor (TNF) was studied in vitro on human endothelial cells. TNF (1-1000 pg/ml) induced a dose-dependent increase in PAI level in the supernatant from 6 to 25 U/ml as estimated against urokinase. This effect was time-dependent. It was not suppressed by Polymyxin B thus excluding a possible contribution of an endotoxin contamination. Fibrinoenzymography performed after SDS-PAGE showed that this inhibitor neutralized urokinase and tissue plasminogen activator and gave rise to high molecular weight complexes. TNF (30 micrograms/kg) was also injected in rat. Blood fibrinolytic activity determined 4 hr later was decreased as estimated by the prolongation of the euglobulin clot lysis time from 37 to 188 min. Fibrinoenzymographic profile of the plasma was then characterized by a fainting of the tPA lysis band but the capacity of plasma to neutralize urokinase was not significantly modified. These results suggest that TNF could alter the fibrinolytic balance by stimulating PAI production at the endothelial level. This might be of importance in synergy with the TNF-induced procoagulant activity for promoting vascular occlusion of tumor capillaries.

Animals↗
PubMed1988

Induction of tumour necrosis factor by staphylococcal toxic shock toxin 1.

Staphylococcal toxic shock syndrome toxin 1 (TSST1) induced the release of tumour necrosis factor (TNF) from human and rabbit monocytes in vitro. Nanogram amounts of TSST1 were sufficient to induce TNF release. There was considerable variation in response between cells from different rabbits and different donors. Rabbit monocytes were slightly more sensitive to TSST1 than were human monocytes. Release of TNF in vivo could explain many of the symptoms of toxic shock syndrome.

Adult↗
PubMed1987

Induction of human interleukin-1 production by polymyxin B.

Lipopolysaccharide (LPS) is a well known interleukin-1 inducer. Polymyxin B sulphate (PMB) is a cyclic antibiotic which neutralizes different biological properties of LPS. Under the conditions used in our laboratory, we were able to show that PMB alone could stimulate human monocytes to produce and release interleukin-1 activity, and that PMB was unable to inhibit the production of interleukin-1 by human monocytes stimulated with LPS. On the contrary, a synergistic effect was obtained which was not observed with another stimulant such as muramyl dipeptide.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Enhanced oxidative burst without interleukin 1 production by normal human polymorphonuclear leukocytes primed with muramyl dipeptides.

Purified polymorphonuclear (PMN) cells were obtained from human blood leukocytes by centrifugation on colloidal silica gradients. PMNs could be primed for PMA-triggered oxidative burst by muramyl peptide molecules (MDP) and two of its adjuvant active nonpyrogenic derivatives. The priming effect of MDP could be demonstrated after a 1-h incubation period, whereas monocytes needed an 18-h incubation to produce an enhanced response in the NBT reduction test. Only the monocyte-enriched population was able to produce IL-1 activity after muramyl peptide stimulation. Under such conditions, PMNs neither produced nor secreted IL-1-like activity, and no IL-1 inhibitor was present in the supernatant fluids. In conclusion, muramyl peptides were able to prime PMNs for oxidative burst but not to stimulate IL-1-like factor production.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Dose-dependent efficacy of vaccination against K. pneumoniae in high and low antibody responder lines of mice.

Innate and acquired resistance to Klebsiella pneumoniae infection were investigated in high (HI) and low (LI) antibody responder lines of mice. The two lines were very susceptible to infection since even small inoculum doses of a virulent strain provoked a 100% mortality within a few days. However the mean survival time was significantly longer in LI than in HI. (HI X LI) F1 hybrids were more resistant than both parental lines. Immunization with heat killed K. pneumoniae was able to confer full protection on the mice in the two lines. However there was a large difference in the number of killed bacteria required to induce the protective effect in HI and in LI mice. The dose-effect relationship for protection correlated with that of antibody production. The protective role of antibodies was confirmed by the survival of HI and LI mice, when antibodies were passively given prior to lethal challenge. The results are in agreement with the fact already demonstrated, that the defect of LI mice in antibody responsiveness is a quantitative one. Therefore a satisfactory immune protection against K. pneumoniae could be obtained in LI mice by adapting the vaccination procedure.

Animals↗
PubMed1987

[Protective effect of tumor necrosis factor (TNF) obtained by genetic recombination against experimental bacterial or fungal infection].

Recombinant human tumor necrosis factor (rHuTNF) enhanced nonspecific resistance of mice to various bacterial and fungal infections, indicating that the protective effect previously reported by us with serum TNF (sTNF) prepared in mice, could be attributed to this macrophage-derived factor. Comparative assays with both TNF preparations have shown that the protection against the infections challenges was largely correlated with antitumor activity. The protective effect of the rHuTNF preparation, expressed from a cDNA clone in Escherichia coli, was not due to contaminating endotoxin products. Since recombinant TNF and sTNF have no direct bactericidal or anti-fungal activity, the enhanced resistance to infections can be explained by the action of TNF on macrophages and polymorphonuclear cells. The experimental data support the interpretation that TNF has an important role in nonspecific immunity.

Animals↗
PubMed1986

Dissociation between muramyl dipeptide-induced fever and changes in plasma metal levels.

A fall in plasma iron level and an increase in copper level were observed in rabbits subsequent with the febrile response induced by an intravenous administration of muramyl dipeptide, AcMur-L-Ala-D-isoGln (MDP). The pyrogenic activity of MDP was due partly to the induction of circulating endogenous pyrogen (EP). EP produced in vitro by activated macrophages also elicited changes in iron and copper levels in rabbits. Nonpyrogenic MDP derivatives murabutide [MDP(Gln)-OnBu] and the stereoisomer of MDP [MDP(D,D)] did not cause any change in blood metal levels. Another adjuvant and nonpyrogenic analogue, murametide [MDP(Gln)-OMe], elicited hypoferremia and hypercupremia. Murametide, which has been previously shown to induce secretion of circulating EP but prevents in vivo fever response, was unable to prevent an EP-induced effect on plasma metal concentrations. Injection of supernatant fluids of macrophages incubated with these different glycopeptides showed that only compounds able to induce EP release were capable of evoking hypoferremia and hypercupremia. The EP-containing fluid was 10-fold more active on change in temperature and in plasma metal levels when it was given intracerebroventricularly compared with intravenously. In contrast, a pyrogenic dose of MDP that can act directly on the central thermoregulatory structures did not modify iron and copper levels when it was injected intracerebroventricularly.

Acetylmuramyl-Alanyl-Isoglutamine↗