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Biomedical subjects

L Chedid

Publications and source records attributed to L Chedid.

At least 109 records · Page 6Linked to original sources
PubMed1983

In vitro effects of lipopolysaccharides and mycobacterial cell wall components on swine alveolar macrophages.

The possible activation of swine alveolar macrophages (AM) by lipopolysaccharides (LPS) and mycobacterial cell wall components such as muramyl dipeptide (MDP) and interphase material (IPM) was investigated. Swine AM were harvested by post mortem lung washings and the following functions were assayed: adherence and spreading in cultures; phagocytosis of 51Cr-labelled chicken red cells; cytostatic activity against xenogeneic tumour cells (P815 mastocytoma cells); monokine synthesis; interferon and LAF (lymphocyte activating factor or interleukin-1). Incubation of swine AM with either MDP, LPS or IPM (0.1 micrograms to 100 micrograms/ml) for 24 hours did not affect the cell viability but increased their adherence and spreading slightly. Phagocytosis was not markedly modified. Under the same experimental conditions, the unstimulated AM cultures exhibited a strong cytostatic activity which was not modified by these components. No interferon synthesis could be observed in the normal or stimulated AM cultures. In contrast, LAF activity was consistently increased after 48 hours of incubation with LPS, whereas MDP produced this effect only in some experiments.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Lack of general immunosuppression during visceral Leishmania tropica infection in BALB/c mice: augmented antibody response to thymus-independent antigens and polyclonal activation.

Leishmania tropica causes a lethal visceral disease in highly susceptible BALB/c mice, with many immunopathologic features resembling those in human kala-azar. The responses to thymus-independent antigens of Type 1 and 2 (TI-1, TI-2) were compared in infected mice of susceptible BALB/c and resistant C57BL/6 strains at various times after infection. The infected BALB/c mice had an augmented response to both types of antigens at 45 days after infection. Later (day 76), the response to trinitrophenylated lipopolysaccharide (TNP-LPS, a TI-1 antigen) was diminished but that to dinitrophenylated Ficoll (DNP-Ficoll, a TI-2 antigen) remained statistically above the response of uninfected mice. The response of the resistant strain to either antigen was not modified as a result of the infection. Both strains showed significant polyclonal activation, which was considerably greater in the BALB/c than in the C57BL/6 mice. The observations presented here are in contrast to the widely held belief that a generalized nonspecific immunosuppression occurs in L. tropica infected BALB/c mice.

Animals↗
PubMed1983

[Demonstration of a bacterial structure in two human mediators: a sleep facilitating factor and a monokine].

A monoclonal anti-MDP antibody was found to bind to "Slow Wave Sleep" factor. This result confirms that this factor is a muramyl peptide and furthermore shows that it contains a structure characteristic of the synthetic adjuvant and of the bacterial cell wall, i.e. an acetylated muramic acid bound to L-alanine. This antibody was also shown to specifically inhibit a biological activity of a purified human monokine which induces fever. Because of these results and other recent observations we propose that a bacterial structure is present in certain mammalian mediators.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

[Enhancement of the activity of hepatitis B virus vaccine by association with murabutide].

Murabutide (N-acetyl-muramyl-L-alanyl-D-glutamine-alpha-butylester), an MDP analogue, is a potential adjuvant for Human immunization. High levels of specific antibodies were obtained in Mouse and Guinea-Pig following administration with murabutide of low dosages of anti-hepatitis B viral vaccine containing the surface antigen (HBs). The effect of murabutide was enhanced without increasing the level of specific IgE by association with suboptimal dosages of aluminium hydroxide.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Demonstration of muramyl dipeptide (MDP)-induced T suppressor cells responsible for MDP immunosuppressive activity.

Muramyl dipeptide (MDP), a synthetic immunostimulant, has been previously shown to increase or decrease the humoral and cellular immune responses, depending upon the experimental conditions used. In the present study we have investigated the mechanisms of MDP-induced immunosuppression. After repeated injections of high dosages of MDP in vivo, both adherent and B cell-enriched cell populations from MDP-treated mice were able to collaborate with normal complementary populations. In contrast, T cell-enriched populations exhibited suppressive activity which could be removed by treatment with anti-Thy-1.2 antiserum and complement. These results clearly indicate that MDP-induced immunosuppression is mediated by T cells.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Analysis of the antigenic relationship of various derivatives of n-acetyl-muramyl-l-ala-d-isoglutamine (MDP), using anti-MDP antibodies.

Antibodies to N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) were produced in rabbits by injection of MDP conjugated to various carriers [bovine gamma globulin (BGG), methylated BSA or sheep erythrocytes]. The anti-MDP was assayed by a direct enzyme-linked immunosorbent assay (ELISA) using horse radish peroxidase linked to MDP-Lys. Various derivatives of MDP were employed in an inhibition of ELISA for analysis of specificity of antibodies and study of the relationship of configuration to biological activity. The results confirmed previous findings that MDP alone is not immunogenic but can act as a hapten when conjugated to carriers. The antibodies were shown to be primarily directed against the muramyl residue. Modifications of this region of MDP yielded derivatives with weak reactivity against anti-MDP, while some changes of other regions had no effect on its antigenicity. Optical isomers of MDP had reduced activity as compared to MDP and polymeric MDP was a strong inhibitor. The structure and function relationship is discussed for some derivatives.

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↗
PubMed1982

Fate of two 14C labelled muramyl peptides: Ac-Mur-L-Ala-gamma-D-Glu-meso-A2pm and Ac-Mur-L-Ala-gamma-D-Glu-meso-A2pm-D-Ala-D-Ala in mice. Evaluation of their ability to increase non specific resistance to Klebsiella infection.

The metabolic fate in mice of two 14C labelled meso-A2pm containing muramyl-peptides, the muramyl-tripeptide (Ac-Mur-L-Ala-gamma-D-Glu-14C-meso-A2pm) (MTP) and the muramyl-pentapeptide (Ac-Mur-L-Ala-gamma-D-Glu-meso-A2pm-14C-D-Ala-14C-D-Ala) (MPP) has been studied. As with 14C-MDP, the radioactive muramyl-tripeptide and muramyl-pentapeptide disappear rapidly from the organs and the radioactivity is found mainly in the urine. In contrast to MDP, the two meso-A2pm containing muramyl-peptides are not excreted intact in the urine. In both cases labelled fragments have been identifed: meso-A2pm from MTP and the tetrapeptide gamma-D-Glu-meso-A2pm-D-Ala-D-Ala from MPP. The ability of the two muramyl-peptides to increase nonspecific resistance of mice to Klebsiella infection was also investigated. The muramyl-pentapeptide injected i.v. one day before a lethal dose of K. pneumoniae protects both adult and neonate mice, as does MDP itself; the muramyl-tripeptide is inactive.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Successful immunization with a totally synthetic diphtheria vaccine.

Three peptides corresponding to fragments of diphtheria toxin have been synthesized. They include the previously described tetradecapeptide and two structural analogs, the hexadecapeptide and the octadecapeptide. Conjugates of these peptides to proteins or a synthetic carrier have induced in guinea pig protection against the dermonecrotic activity of diphtheria toxin. All of the conjugates were immunogenic when administered either in complete Freund's adjuvant or with N-acetylmuramyl-L-alanyl-D-isoglutamine in aqueous medium. Positive immune response toward the octadecapeptide was obtained in mice as well. In this case, the immunogenic combinations were conjugates with bovine serum albumin administered either in Freund's adjuvant or with the muramyl dipeptide and a complete synthetic conjugate comprising both the octadecapeptide and the muramyl dipeptide covalently attached to a synthetic carrier, multichain poly(DLAla). This last immunogen, which induced the most effective immune response, is a completely synthetic immunogen with built-in adjuvanticity and induces protective antitoxic immunity when administered in a physiological medium.

Adjuvants, Immunologic↗
PubMed1982

Immunological castration of male mice by a totally synthetic vaccine administered in saline.

It had been reported that immunological neutralization of the hypothalamic luteinizing hormone-releasing hormone (LH-RH) can be achieved by injection of the synthetic hormone, a decapeptide, linked to a carrier and administered with Freund's complete adjuvant. Data presented here demonstrate that the resulting immunological castration can be obtained by administering in an aqueous medium the synthetic decapeptide directly conjugated to the synthetic immunomodulator glycopeptide N-acetylmuramyl-L-alanyl-D-isoglutamine. In the group receiving the conjugate, a higher titer of anti-LH-RH antibodies was obtained than in the group receiving LH-RH in Freund's emulsion. Moreover, histological examination showed that seminiferous tubules were atrophied and that no spermatozoides could be observed. This procedure could lead to applications in the veterinary field and also serve as a useful model for other antiviral or antibacterial synthetic vaccines.

Animals↗
PubMed1982

Visceral Leishmania tropica infection of BALB/c mice: cellular analysis of in vitro unresponsiveness to sheep erythrocytes.

In mice, infection with Leishmania tropica initially produced a nonspecific enhancement of the immune response to sheep erythrocytes as measured both in vitro and in vivo. Subsequently, the spleen cell responses of susceptible mice (BALB/c) to sheep erythrocytes and T- and B-cell mitogens in vitro decreased dramatically, whereas those of the resistant strain (C57BL/6) returned to normal. Analysis of the spleen cells of infected animals revealed that macrophages (the target cells of Leishmania) were not defective. However, both T- and B-cell-depleted splenocyte populations of infected animals lacked the ability to respond in the presence of their corresponding B- and T-cell-depleted populations of normal spleen cells. It was also observed that the addition of various numbers of Leishmania organisms did not alter the response of normal spleen cells in vitro. The results of cocultures of various ratios of cells from the spleen of infected and normal animals ruled out the possibility of a strong active immunosuppression. The decrease of in vitro response is attributed to the depletion of immunocompetent cells in the spleen of infected mice, which is heavily populated by null cells.

Animals↗
PubMed1982

Absence of antibodies to muramyl dipeptide in patients with tuberculosis or leprosy.

The enzyme-linked immunosorbent assay (ELisa) was used to detect the presence of antibodies to muramyl dipeptide (MDP) in serum of patients with leprosy or tuberculosis. Using a conjugate of MDP-lysine to horse radish peroxidase, no such antibodies could be detected in sera of either patients or controls. Antibodies to a sonicate antigen of Mycobacterium tuberculosis were found in sera of all individuals tested and the binding of these antibodies to the M. tuberculosis antigen could not be inhibited by MDP. On the other hand, binding of MDP to anti-MDP antibodies, raised in rabbits, was largely inhibited by free MDP, slightly inhibited by M. tuberculosis antigen and was not inhibited by the patients' sera.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Adjuvant polyarthritis. V. Induction by N-acetylmuramyl-L-alanyl-D-isoglutamine, the smallest peptide subunit of bacterial peptidoglycan.

N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), an apparently nonimmunogenic bacterial peptidoglycan-derived small peptide, was found to induce a polyarthritis the rat similar to that induced by Freund's complete adjuvant when injected in the form of an oil emulsion. An oil emulsion of its isomer, N-acetylmuramyl-L-alanyl-L-isoglutamine, which unlike MDP has no immunostimulatory activity, failed to induce the disease.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Active antitoxic immunization by a diphtheria toxin synthetic oligopeptide.

Diphtheria toxin (DT) is a single polypeptide chain of molecular weight 62,000 with two disulphide bridges. Immunization against diphtheria rests on the stimulation of antibodies against detoxified toxin which also combine with the native toxin. Because the antibodies differ functionally from each other, however, only some of them are able to neutralize toxicity. We have therefore set out to synthesize part of the amino acid sequence of the toxin whose function as a stimulator of antibodies might be less ambiguous, and have chosen the loop of 14 amino acids subtended by the disulphide bridge nearer the NH2 terminus of the molecule (Fig. 1). There is reason to think that this loop may be involved in the toxicity and immunological specificity of the molecule. We report here our finding that the tetradecapeptide (residues 188-201), when linked covalently with two different carriers, will elicit in guinea pigs antibodies which not only bind specifically with the toxin but neutralize its dermonecrotic and lethal effects. To our knowledge these results constitute the first example of successful active immunization against a lethal bacterial toxin using a synthetic antigen.

Amino Acid Sequence↗
PubMed1981

Properties of reference Escherichia coli endotoxin and its phthalylated derivative in humans.

The properties of a reference bacterial endotoxin prepared from Escherichia coli and its phthalylated derivative were studied in normal human volunteers infected intravenously with the compounds. The minimal pyrogenic dose of the reference endotoxin is about 0.1-0.5 ng/kg. The increase in white blood cell count, absolute granulocyte count, absolute immature granulocyte count, and concentrations of serum amyloid A, cortisol, and growth hormone was directly related to the concentration of reference endotoxin administered. Phthalylated reference endotoxin up to 1,000 ng/kg (at least 500 ng of the patent compound/kg) was administered to normal human volunteers without significant changes in temperature, white blood cell count, absolute granulocyte count, and concentrations of serum amyloid A, cortisol, and growth hormone. Thus, this study defines biologic properties of the new reference bacterial endotoxin in humans and demonstrates effective detoxification by phthalylation of the present compound.

Adult↗
PubMed1981

Increased resistance and depressed delayed-type hypersensitivity to Listeria monocytogenes induced by pretreatment with lipopolysaccharide.

Intravenous injection of a small dose of lipopolysaccharide 24 h before infection with Listeria monocytogenes enhanced the resistance of mice to this organism. This protective effect of lipopolysaccharide related to the ability of nonimmune macrophages to inhibit bacterial proliferation in livers and spleens. Surprisingly, lipopolysaccharide-treated mice exhibited inferior acquired immunity, as measured by adoptive transfer of immunity to normal mice, delayed-type hypersensitivity to Listeria antigens, and uptake of tritiated thymidine by lymphocytes in the spleen. These results support the view that lipopolysaccharide stimulates a highly effective anti-Listeria immunity via the macrophage component, despite interference with the lymphocyte component.

Animals↗