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Biomedical subjects

L Chedid

Publications and source records attributed to L Chedid.

At least 145 records · Page 8Linked to original sources
PubMed1979

In vivo activation of murine peritoneal macrophages by Nocardia water soluble mitogen (NWSM).

In vitro NWSM has been shown to be a B cell mitogen and a polyclonal activator. Although NWSM has been also shown to be adjuvant active in vivo, motogenicity and polyclonal activation are not observed when this fraction has been administered to mice. In contrast, the experiments reported here demonstrate that after in vivo administration several effects of NWSM on mouse peritoneal macrophages can be observed: NWSM was able to induce an important increase in the ability of peritoneal macrophages to inhibit in vitro growth of tumor cells, to increase their phagocytic activity and to enhance their ability to induce an immune response, following the incubation with an antigen NWSM was able to stimulate phagocytic activity of macrophages of C3H/He Orl. mice (LPS-resistant strain). Those findings suggest that the adjuvant activity of NWSM in vivo can be related to its capacity to activate macrophages.

Adjuvants, Immunologic↗
PubMed1979

Fate of the synthetic immunoadjuvant, muramyl dipeptide (14C-labelled) in the mouse.

Synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide or MDP) represents the smallest unit that can substitute for whole Mycobacteria in Freund's complete adjuvant. In this paper the fate of 14C-labelled (on the muramyl moiety) MDP is reported. Following intravenous or subcutaneous injection into mice, more than 50% of 14C-MDP was recovered in the urine after 30 min and more than 90% after 2 h. The labelled compound was found unchanged in the urine, as shown by detailed analyses. However, MDP was sequestered for a longer time at the site of injection when administered as a water-in-oil emulsion. Considering the relatively rapid elimination observed, it is suggested that the biological effects of MDP and related compounds, when administered in an aqueous medium, may be due to their activity at minute concentrations and/or an immediate action at the cellular level.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Enhancement of certain biological activities of muramyl dipeptide derivatives after conjugation to a multi-poly(DL-alanine)--poly(L-lysine) carrier.

N-Acetylmuramyl-L-Ala-D-Glu-NH2 (muramyl dipeptide) and several of its derivatives are effective immunoactivators that can enhance nonspecific resistance to infection but can also elicit fever. In contrast, one of its stereoisomers, N-acetylmuramyl-D-Ala-D-Glu-NH2, is devoid of both these activities. Our present report demonstrates that macromolecularization of muramyl dipeptide by attachment of several units to a multi-poly(DL-Ala)-poly(L-Lys) carrier potentiates both its pyrogenic and its immunostimulant activity. This branched polymer has been extensively used as carrier to various haptens. Surprisingly, inactive N-acetylmuramyl-D-Ala-D-Glu-NH2, after conjugation under the same conditions, becomes capable of increasing nonspecific immunity although its lack of pyrogenicity is not greatly modified. Moreover, the N-acetylmuramyl-D-Ala-D-Glu--NH2 conjugate remains devoid of adjuvant, sensitizing, or eliciting activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Transfer by bone marrow cells of increased natural resistance to Klebsiella pneumoniae induced by lipopolysaccharide in genetically deficient C3H/He mice.

In a previous study we demonstrated that lipopolysaccharide failed to elicit nonspecific resistance in C3H/He lipopolysaccharide low-responder mice against Klebsiella infection in contrast to its activity in a closely related histocompatible high-responder subline, C3HeB/Fe. Complete restoration of lipopolysaccharide-induced protection against 10(5) Klebsiella was obtained in the present study by transferring bone marrow from high-responder mice to the highly deficient C3H/He mice. The ability of C3H/He mice to clear and destroy bacteria in 5 h was also transferred by C3HeB/Fe marrow cells. In contrast, when high-responder C3HeB/Fe mice were reconstituted with low-responder bone marrow, the clearance and destruction of K. pneumoniae were similar to what is observed in the high-responder strain, but survival was only temporary. Collectively, our data show that the failure of C3H/He mice to respond to lipopolysaccharide with nonspecific immunity is due to a defect in two types of bone-marrow-derived cells--radioresistant and radiosensitive.

Animals↗
PubMed1979

Enhancement by muramyl dipeptide of in vitro nude mice responses to a T-dependent antigen.

N-acetyl-muramyl-L-alanyl-D-isoglutamine (referred to as MDP for muramyl dipeptide) has been shown to enhance in vivo and in vitro immune responses to various antigens. It has previously been reported that in the case of T-dependent antigens, the adjuvant activity of MDP was mediated by a helper T-cell. Our present findings demonstrate that in vitro responses of nude mice spleen cells to T-independent, TNP-PAA or T-dependent SRBC can also be markedly increased by this synthetic adjuvant. Moreover, under the same conditions, MDP produced polyclonal activation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Effect of cell division inhibitors on polyclonal activation can vary according to the target cell used.

The effects of inhibitors of cell division on polyclonal stimulation induced either by bacterial lipopolysaccharide (LPS) or by a synthetic adjuvant, MDP, were compared, using different target cells. Doses of colchicine that prevented 3H-thymidine incorporation also prevented the induction of antibodies against TNP and against an altered self antigen: bromelain-treated mouse red blood cells (br-MRBC). Under identical conditions, incubation with cytosine arabinoside (CA) strongly prevented the induction of anti-TNP PFC and to a lesser degree anti-SRBC PFC. However, the number of anti br-MRBC PFC was unchanged even when a dose of CA which inhibits totally the incorporation of 3H-thymidine was used. Our findings indicate that the general term "polyclonal stimulation" may concern at least two different types of cell populations and therefore we strongly stress the importance of choosing similar targets in comparative experiments.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

[Increase of non-specific resistance to infection by synthetic adjuvants].

MDP and some other synthetic glycopeptides which are endowed with adjuvant properties are also able to increase non-specific resistance of mice to bacterial infections. They are effective by various routes including the oral route, and this protective activity can be demonstrated in animals having a poor immune status.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Macrophage activation by mycobacterial water soluble compounds and synthetic muramyl dipeptide.

The adjuvant effects of mycobacteria can be replaced by more chemically defined isolates of the cell walls including a water soluble fraction (WSA) and by the synthetic analog N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), which is the minimal structure required for adjuvanticity. These compounds can directly activate macrophages as determined by an increase in spreading and adherence and by an elevated synthesis of the enzyme collagenase. Moreover, this increase in collagenase production is modulated by enhanced production of prostaglandins that influences intracellular levels of cyclic AMP. In addition, both MDP and WSA induced macrophages to produce a biologically active mediator that triggers quiescent fibroblasts into active proliferation. It thus appears that a mechanism for mycobacterial adjuvant action as determined with MDP and WSA is via activation of macrophages, which may then precipitate a multiplicity of other reactions resulting in enhanced immune phenomena. Furthermore, the granulomatous and fibrotic reactions associated with mycobacterial infection may be a consequence of this direct activation of macrophages.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1978

The macrophage, target cell of the synthetic adjuvant muramyl dipeptide.

The mechanism of adjuvant activity of the synthetic glycopeptide N-acetylmuramul-L-alanyl-D-isoglutamine or muramyl dipeptide (MDP) was studied using in vitro plaque-forming cell (PFC) response to sheep erythrocytes (SRBC). Addition of MDP to DBA/2 mouse spleen cell cultures resulted regularly in a 2 to 3-fold increase of PFC numbers/10(6) recovered cells (p less than 0.01). Supernates (SPN) from MDP-stimulated cultures added to standard spleen cell + SRBC cultures brought about even more important increases of PFC numbers (p less than 0.01 to p less than 0.001). SPN from cultures supplemented with MDP alone (without SRBC) were more active than those of cell + MDP + SRBC cultures, and SPN removed on day 3 of culture were more active than those of day 5. This activity of SPN was maintained accross an H-2 histocompatibility barrier. Although pretreatment of spleen cells with anti-theta antigen serum entirely suppressed the anti-SRBC PFC response in spite of the presence of MDP, SPN from these cultures were as active as SPN from normal spleen cell MDP-stimulated cultures. In contrast, pretreatment of spleen cells with specific rabbit anti-mouse macrophage serum entirely suppressed both anti-SRBC response and SPN activity. It was concluded that the target cell for MDP is the macrophage which releases factors ultimately acting on B cells through T cell mediation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1978

Enhancement of the neonate's nonspecific immunity to Klebsiella infection by muramyl dipeptide, a synthetic immunoadjuvant.

N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) and certain derivatives that are structural analogs of part of the bacterial peptidoglycan monomer have been shown to be adjuvant active and to enhance the nonspecific immunity of adult mice infected by Klebsiella pneumoniae. In the present study muramyl dipeptide and two other synthetic analogs were found to be active in newborn mice. This activity could be demonstrated after administration by subcutaneous or even by oral route. In contrast to what was observed after treatment by lipopolysaccharide, 8-day-old mice were definitively protected against bacterial challenge by these glycopeptides. Therefore such molecules could have a great value in view of studying and correcting the neonate's unresponsiveness.

Adjuvants, Immunologic↗