Biomedical subjects

G Riveau

Publications and source records attributed to G Riveau.

17 recordsLinked to original sources

PubMed1994

Construction, expression, and immunogenicity of the Schistosoma mansoni P28 glutathione S-transferase as a genetic fusion to tetanus toxin fragment C in a live Aro attenuated vaccine strain of Salmonella.

A vector has been constructed to allow genetic fusions of guest antigens via a hinge domain to the C terminus of the highly immunogenic C fragment of tetanus toxin. A fusion has been constructed with the gene encoding the protective 28-kDa glutathione S-transferase (EC 2.5.1.18) from Schistosoma mansoni. The recombinant vector has been electroporated into the nonvirulent Salmonella typhimurium aroA live vaccine strain SL3261. The corresponding chimeric protein is stably expressed in a soluble form in Salmonella as evaluated by Western blotting with fragment C and glutathione S-transferase antisera. Mice immunized intravenously with a single dose of the live recombinant bacteria elicit antibodies to both fragment C and glutathione S-transferase as detected by enzyme-linked immunosorbent assays. Furthermore, all of the mice were solidly protected when challenged with lethal doses of either tetanus toxin or the virulent Salmonella typhimurium strain C5. Mice have also elicited antibodies to fragment C and glutathione S-transferase after oral immunization. It may be that a live trivalent vaccine against typhoid, tetanus, and schistosomiasis is feasible.

Animals↗

PubMed1994

Surface-associated filamentous hemagglutinin induces autoagglutination of Bordetella pertussis.

Filamentous hemagglutinin (FHA) is a major adhesin produced by Bordetella pertussis, the etiologic agent of whooping cough. FHA has been shown to be surface associated but is also secreted by virulent bacteria. Microscopic observations of lungs of mice infected with B. pertussis showed that the bacteria grow as clusters within the alveolar lumen. When B. pertussis was cultivated in vitro with chemically defined medium, bacteria grew as aggregates, mimicking growth observed in vivo. This aggregation was abolished by the addition of cyclodextrin (CDX) to the growth medium and depended on the production of FHA, because a mutant lacking the FHA structural gene failed to form aggregates in a CDX-free medium. Western blot (immunoblot) analyses revealed that, in the absence of CDX, FHA was attached to the bacterial surface and was not efficiently released into the growth medium. Hydrophobic chromatography of FHA showed that CDX drastically reduced the hydrophobicity of FHA, suggesting a direct binding of CDX to FHA, which was further supported by the partial protection of FHA from trypsin digestion in the presence of CDX. In addition, free FHA can interact in a CDX-inhibitable manner with solid phase-immobilized FHA. It can therefore be postulated that the B. pertussis aggregates are most likely due to direct FHA-FHA interaction.

Adhesins, Bacterial↗

PubMed1994

Development of a vaccine strategy against human and bovine schistosomiasis. Background and update.

Two specific characteristics of schistosome infection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive hosts (unlike protozoan parasites) and a partial non-sterilizing immunity can have a marked effect on the incidence of pathology and on disease transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reduction in parasite burden is a sufficient goal for vaccine induced immunity. We originally showed that IgE antibodies played in experimental models a pivotal role for the development of protective immunity. These laboratory findings have now been confirmed in human populations. Following the molecular cloning and expression of a 28 kDa protein of Schistosoma mansoni and its identification as a glutathione-S-transferase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction in parasite burden, vaccination with Sm28 GST was recently shown to reduce significantly parasite fecundity and egg viability leading to a decrease in liver pathology. Whereas IgE antibodies were shown to be correlated with protection against infection, IgA antibodies have been identified as one of the factors affecting egg laying and viability. In human populations, a close association was found between IgA antibody production to Sm28 GST and the decrease of egg output. The use of appropriate monoclonal antibody probes made it possible to demonstrate that the inhibition of parasite fecundity following immunization was related to the inhibition of enzymatic activity of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Production and enhanced anti-tumor activity of tumor necrosis factor in mice treated with cyclophosphamide.

We demonstrated recently that the production of tumor necrosis factor (TNF) is induced in normal mice and in the immunosuppressed nude mouse model by the administration of muramyl dipeptide (MDP) derivatives followed by endotoxin (lipopolysaccharide). In the present study, the ability of this treatment to induce the production of TNF in mice receiving cyclophosphamide (CY) was examined. Two days following treatment with high-dose CY (250 mg/kg), mice exhibited leukocytopenia and drastically reduced splenic weight. However, these animals remained capable of producing TNF, albeit at lower levels, when treated with MDP derivatives and lipopolysaccharide (LPS), particularly when the lipophilic analogue MDP-dipalmitoyl glycerol (GDP) was utilized. TNF was also induced by the administration of MDP-GDP and LPS to Meth A sarcoma-bearing mice treated with this dose of CY. Furthermore, in all animals receiving this combination therapy, sarcoma necrosis and complete regression were obtained without any sign of tumor regrowth. A dose of 100 mg/kg CY was not effective for inhibiting tumor regrowth under the same experimental conditions. These results demonstrated that the anti-tumor activity of endogenously induced TNF is potentiated by combined therapy with a high dose of CY.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1989

Interleukin-1-induced sleep and febrile responses differentially altered by a muramyl dipeptide derivative.

Muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine; AcMur-L-Ala-D-iGln; MDP) is a somnogenic, pyrogenic, and immunoadjuvant component of bacterial cell wall peptidoglycan. It enhances the production of the cytokine interleukin 1 (IL-1) in vivo and in vitro; IL-1 itself is somnogenic and pyrogenic. The pyrogenic effects of IL-1 may be separated from its somnogenicity by the use of antipyretics. A methyl ester derivative of MDP (murametide; AcMur-L-Ala-D-Gln-alpha-methyl ester) blocks IL-1-induced fever, but induces IL-1 production/release. Therefore, the effects of murametide on IL-1-induced sleep and fever responses were determined. Rabbits were pretreated with intravenous injections of murametide 0, 30 or 60 min before intravenous injection of a pyrogenic/somnogenic dose of recombinant IL-1 beta (rIL-1 beta). Murametide alone produced no effects on sleep or brain temperatures. Murametide given simultaneously with rIL-1 beta potentiated increases of brain temperatures, whereas when there was a 60 min delay between the injection of murametide and rIL-1 beta, responses were similar to those induced by rIL-1 beta alone. Murametide given 30 min before rIL-1 beta, blocked the expected IL-1-induced fevers but not the rIL-1 beta-mediated increases of slow-wave sleep and decreases of rapid-eye-movements sleep. These results reinforce the conclusion that, in part, independent brain mechanisms are involved in the somnogenic and pyrogenic actions of IL-1.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1988

Decrease in pyrogenicity of muramyl dipeptide after coupling with luteinizing hormone-releasing hormone.

Muramyl dipeptide (MDP) and its adjuvant active derivative lysine-MDP (Lys-MDP) have been demonstrated to be pyrogenic and to induce endogenous pyrogen (EP) production in vivo and in vitro. It has recently been shown that immunologic castration can be achieved in mice by immunization with luteinizing hormone-releasing hormone (LHRH) directly conjugated by carbodiimide to Lys-MDP, termed LHRH-Lys-MDP (cdi), or with a linear monomeric MDP-linked molecule obtained by total synthesis, termed LHRH-Lys-MDP (s). These preparations were tested in the rabbit for their capacity to induce fever and were found to be devoid of pyrogenicity at dosage levels of Lys-MDP that induced fever. This decrease of pyrogenicity of Lys-MDP after coupling to LHRH seems to be related to the structure of the conjugate because the derivative LHRH-LysNH2-MDP exhibited the same pyrogenic activity as the free glycopeptide. Surprisingly, nonpyrogenic LHRH-Lys-MDP induced production of EP and interleukin-1 (IL-1) in vitro and increased in vivo modifications of metal levels attributed to the action of IL-1. Moreover, LHRH-Lys-MDP reduced the pyrogenic effect of an exogenous dose of EP.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1987

Differential effect of MDP treatment on magnesium in rat tissues.

Magnesium determinations were performed by atomic absorption spectrophotometry on several tissues of MDP-treated and control rats. Sixteen hours after a single administration of 1 mg of MDP, Mg concentrations were increased in both the liver and the adrenals. After three daily injections of the same MDP doses, statistically significant increases of Mg concentration were observed in the liver, the brain and the adrenals. For the latter, however, the results were significant only when Mg concentrations were referred to the weight of tissue water but not when they were referred to the dry weight. Blood, thymus, spleen, kidneys, cardiac and skeletal muscle Mg determinations were also performed; no significant effect of MDP has been observed under our experimental conditions. The present results show that MDP modifies the distribution of Mg in various compartments of the body and suggest the possible role of Mg in some biological actions of MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗

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↗

PubMed1985

Production of differentiation-stimulating factor for murine leukemic myeloblast line by monocytic cells stimulated by a nonpyrogenic muramyl dipeptide derivative.

Muramyl dipeptide (MDP) and adjuvant-active derivatives were confirmed as unable directly to induce differentiation of mouse myeloid leukemia M1 cells. They were, however, found effective in stimulating either rabbit macrophages or human blood monocytes to produce differentiation-stimulating activity (D factor). The various conditioned media (CM) thus obtained were able to induce differentiation of the myeloblastic M1 cell line as indicated by the appearance of Fc receptors and inhibition of cell proliferation. Among the synthetic glycopeptides inducing the production of D factor, murabutide (MDP[Gln]-OnBu) was as effective as MDP, although it did not stimulate monocytes to simultaneously release endogenous pyrogen. The absence of pyrogenicity in murabutide CM was attested by IV or intracerebroventricular administration to rabbits. However, in the same CM, LAF(IL1) activity estimated by potentiation of the in vitro proliferative response to phytohemagglutinin of mouse thymocytes was usually higher than that induced by MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1984

Changes in rabbit febrile responses to muramyl dipeptide (MDP) after coupling to a synthetic carrier.

Muramyl dipeptide (MDP) is a small molecular weight synthetic glycopeptide (less than 500), which has been shown to be an immunoadjuvant, and to induce a biphasic febrile response in the rabbit--probably via the release of endogenous pyrogen--accompanied by a marked leukopenia. Macromolecularization by coupling to a synthetic carrier (MW approximately or equal to 60,000) potentiates the immunostimulant properties of MDP but also its pyrogenicity. The present study demonstrates that such a conjugate induced the release of endogenous pyrogen in vivo and in vitro at lower dosage levels than free MDP. Further experiments showed that there existed several differences between free and conjugated MDP. Thus, after intravenous administration of the conjugate, the fever pattern was monophasic with a prompt defervescence and not accompanied by leukopenia at dosage levels inducing similar increase in body temperature. In addition, when fever was recorded after intracerebroventricular administration, the increase in sensitivity was much greater in the case of free MDP than of MDP-A--L.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1984

Specific absorption with monoclonal antibodies to muramyl dipeptide of the pyrogenic and somnogenic activities of rabbit monokine.

It is well established that muramyl dipeptide (MDP) can induce fever and enhance slow-wave sleep. Recently, crude or purified supernatants of activated macrophages containing endogenous pyrogen (EP) were also shown to enhance slow-wave sleep. These similarities and the recent finding that a mammalian factor that enhances slow-wave sleep is a muramyl peptide triggered us to study the possibility of the presence of this bacterial structure in the EP molecule. In the present study, EP was produced by stimulation of rabbit peritoneal cells with a nonpyrogenic, nonsomnogenic analog of MDP. The EP-containing supernatant lost its pyrogenicity and somnogenicity after passage over an immunoadsorbent column of monoclonal anti-MDP but not of another monoclonal antibody of different specificity. High percentage of the EP was recovered by elution of the anti-MDP columns with HCl/glycine buffer. Results suggest that bacterial muramyl peptides may be incorporated by mammalian cells into substances that act in picomole quantities to mediate immunological and physiological processes. In addition, the technique may be useful to extract interleukin 1 for structural studies.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1984

Inhibition of endogenous pyrogen-induced fever by a muramyl dipeptide derivative.

N-acetylmuramyl-L-alanyl-D-isoglutamine, or muramyl dipeptide (MDP), is a synthetic immunoadjuvant analogue of a bacterial peptidoglycan subunit that has a definite pyrogenic effect in the rabbit. Some adjuvant-active derivatives such as murabutide [MDP(Gln)-OnBu] or murametide [MDP(Gln)-OMe] are not pyrogenic. Murabutide did not stimulate human or rabbit cells to release endogenous pyrogen (EP), but murametide induced EP production at the same dosage levels as MDP. Moreover, plasma from rabbits treated with murametide transferred into untreated recipients elicited a febrile response typical of EP fever and comparable with that induced by plasma from MDP-treated animals. Murametide not only inhibited the central effect of EP that is generated but also the effect of an extra dose of EP administered later by the intravenous route. Moreover, pretreatment of rabbits with murametide decreased fever responses induced by certain high-molecular-weight exogenous pyrogens as mediated through the production of EP.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1982

Production of lymphocyte activating factor in the absence of endogenous pyrogen by rabbit or human leukocytes stimulated by a muramyl dipeptide derivative.

N-acetylmuramyl-L-alanyl-D-isoglutamine or MDP is a synthetic immunoadjuvant capable of inducing a febrile response in the rabbit and of eliciting production of endogenous pyrogen (EP) in vivo and in vitro. It was also shown to stimulate in vitro lymphocyte activating factor (LAF) release. After conjugation to a synthetic carrier, the pyrogenic effect of MDP is strongly enhanced. Recently, adjuvant active derivatives of MDP devoid of pyrogenicity such as MDP(Gln)-OnBu (AcMur-L-Ala-D-Gln-alpha-nbutyl ester) have become available. In the present study, their stimulating properties on rabbit peritoneal exudate cells or human peripheral blood mononuclear cells were simultaneously evaluated by testing lymphocyte activating property and pyrogenic effect of the culture supernatant. In both types of cell cultures, whereas MDP elicited dual effects, the nonpyrogenic analog MDP(Gln)-OnBu produced LAF without detectable pyrogenicity even when a very sensitive assay (intracerebroventricular administration) was used. In contrast, conjugated MDP was capable of inducing the production of endogenous pyrogen in rabbit cell cultures with no or little LAF release. These results argue against the possibility that a single factor is responsible for both LAF and EP activities.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1980

Central pyrogenic activity of muramyl dipeptide.

Fever can be elicited in the rabbit by the intravenous administration of relatively large doses of a synthetic immunoadjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine, or muramyl dipeptide (MDP). This response could be mediated by endogenous pyrogen because MDP has been shown to induce their production both in vivo and in vitro. The results reported here show that intracisternal injection of minute amounts of MDP could elevate fever without activating the release of endogenous pyrogen in the plasma or in the cerebrospinal fluid. Moreover, indomethacin inhibited hyperthermia produced by intracerebroventricular administration of MDP. Therefore, our findings argue in favor of a direct effect of the glycopeptide on the thermoregulatory centers besides its indirect effect through the production of leukocytic pyrogen. This molecule apparently represents the minimal requirement for the pyrogenicity of bacterial peptidoglycan because administration, even by the intracerebral route, of a mixture of muramic acid and of its dipeptide moiety did not elicit fever.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1980

Effect of indomethacin on increased resistance to bacterial infection and on febrile responses induced by muramyl dipeptide.

The pyrogenicity in the rabbit and the ability to stimulate nonspecific resistance to bacterial infection in the mouse of muramyl dipeptide (MDP), a synthetic immunoadjuvant, are known to be enhanced when the glycopeptide has been conjugated to a carrier. The effects of indomethacin on fever induced by MDP or its conjugated derivative were studied. Indomethacin reduced febrile responses to MDP or its derivative, although it did not decrease production of endogenous pyrogen in vivo or in vitro. When incubated with rabbit peritoneal cells, indomethacin suppressed the elevation in prostaglandin levels usually induced by MDP. When administered to mice, indomethacin alone stimulated resistance to bacterial infection and, under appropriate conditions, had a strong synergistic effect when combined with free or conjugated MDP. The results demonstrate that neither pyrogenicity nor increased prostaglandin levels are prerequisites for immunopotentiation by synthetic glycopeptides.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1980

Influence of indomethacin on various immunopharmacological effects of muramyl dipeptide (MDP).

Muramyl dipeptide (MDP) is a low molecular (less than 500 daltons) synthetic analogue of a streptococcal peptidoglycan subunit. It was demonstrated to be the minimal structure essential for eliciting the adjuvant effect ascribed to Freund's complete adjuvant (FCA). MDP was likewise shown to represent the minimal requirement for peptidoglycan-induced changes in temperature and it was at first concluded that there was an almost perfect correlation between pyrogenicity and adjuvant activity. However, other experiments showed that certain MDP derivatives were as adjuvant active without eliciting a febrile response in the rabbit. Moreover an anti-inflammatory substance such as indomethacin completely inhibits the pyrogenic effect of MDP but does not affect or even enhance various of its immunostimulant properties. Inhibition of MDP-induced fever is not associated with modification of leucopenia or production of circulating endogenous pyrogens observed after MDP injection. Indomethacin incubated with peritoneal macrophage cultures at a dose which blocks prostaglandin synthesis, does not decrease the production by MDP of endogenous pyrogens.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMedDate not supplied

Development of a vaccine strategy against human and bovine schistosomiasis. Background and update.

Schistosomiasis is a chronic and debilitating parasitic disease that affects over 200 million people throughout the world and causes about 500,000 deaths annually. Two specific characteristics of schistosome infection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive hosts (unlike protozoan parasites) and a partial non-sterilizing immunity can have a marked effect on the incidence of pathology and on disease transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reduction in parasite burden is a sufficient goal for vaccine induced immunity. We originally showed that IgE antibodies played in experimental models a pivotal role for the development of protective immunity. These laboratory findings have been now confirmed in human populations. Following the molecular cloning and expression of a protein 28 kDa protein of Schistosoma mansoni and its identification as a glutathion S-transferase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction in parasite burden, vaccination with Sm28 GST was recently shown to reduce significantly parasite fecundity and egg viability leading to a decrease in liver pathology. Whereas IgE antibodies were shown to be correlated with protection against infection, IgA antibodies have been identified as one of the factors affecting egg laying and viability. In human populations, a close association was found between IgA antibody production to Sm28 GST and the decrease of egg output.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗