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1.
A L Rakhmilevich M S Rakhimova T M Andronova N V Bovin 《Antibiotiki i khimioterapii͡a》1989,34(8):586-589
The effect of muramyldipeptide (MDP), glucosaminylmuramyldipeptide (GMDP) and their six synthetic derivatives on production of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-2 (IL-2) by murine spleen cells in vitro was studied. MDP induced insignificant TNF production and did not stimulate production of IL-1 by the murine splenocytes within a 24-hour cultivation period whereas in combination with lipopolysaccharide (LPS) it induced significant production of both the cytokins. GMDP induced marked production of TNF (54 per cent cytotoxic index) and IL-1 (stimulation index 8). Addition of LPS in an amount of 10 ng/ml increased production of TNF by the murine splenocytes under the effect of GMDP but had no effect on production of IL-1. Neither MDP nor GMDP even in combination with LPS induced production of IL-2 by splenocytes of mice DVA/2 and C57B1/6 at activation for 24 hours. All the synthetic derivatives of MDP and GMDP except the MDP polymer activated TNF production by the murine spleen cells. GMDP lysine had the highest effect: 67 per cent cytotoxic index. In combination with LPS its cytotoxic index amounted to 87 per cent. The TNF activity was always higher when LPS in an amount of 10 ng/ml was added to the glycopeptides. 相似文献
2.
Grabchenko NI Karpov AV Chirva VIa Tkachikova L Spivak NIa 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》2001,(3):50-53
The work deals with the results of experimental evaluation of the influence of some new modified derivatives of muramyldipeptide (MDP) on the course of staphylococcal infection in mice. The preparations under study were found to produce rapid elimination of bacteria from kidneys and the increase of phagocytic activity of blood macrophages in animals. At the same time MDP and its derivatives stimulated natural killer cells whose activity was inhibited during infection. The dependence between the structure of these compounds and their protective action in staphylococcal infection, as well as the increase of the natural immunity characteristics of the body was followed. 相似文献
3.
L V Kozlov L I Rostovtseva T S Lomaka N S Sutovskaia I B Sorokina 《Bioorganicheskaia khimiia》1985,11(11):1510-1518
Along with complement activation by the classical pathway, blastolysin, an antitumor and adjuvant preparation of Lactobacillus bulgaricus peptidoglycans, effectively inhibits the transformation of C3 in to C5 convertase. Values of inhibition maximum and dissociation constants of the reversible C3b-acceptor complex for blastolysin and main immunological active structural moieties of peptidoglycans (GMDP, MDP) and their inactive carbohydrate components (N-acetylglucosaminyl-N-acetylmuramic acid, N-acetylglucosamine, and N-acetylmuramic acid) have been determined. Immunostimulator concentrations for blastolysin, GMDP, and MDP in inhibition of the C5 convertase formation (C3b binding) correlate with their doses in vivo (animal blood), displaying antitumor activity. 相似文献
4.
E A Meshcheriakova S V Gur'ianova E A Makarov T M Andronova V T Ivanov 《Bioorganicheskaia khimiia》1991,17(9):1157-1165
The structure-function relationships in a series of synthetic glucosaminylmuramyl peptides--glycopeptide adjuvants of the bacterial origin--have been investigated. Modification of the N-acetylglucosaminyl-(beta 1-4)-N-acetylmuramyl-L-alanyl-D-isoglutamine (GMDP) molecule affects its adjuvant and pyrogenic activity in vivo. GMDP is shown to readily stimulate the synthesis of the IgG2a and IgG3 of the immunoglobulin subclasses upon the secondary immune response to the protein antigen. The adjuvant effect correlates with the comitogenic test of the reaction of splenocytes blast-transformation in the presence of B-cell mitogen. No direct dependence has been revealed between the level of the glycopeptides adjuvant action and their effect on the IL-1 production by macrophages. 相似文献
5.
A L Rakhmilevich T L Migdal M S Rakhimova M A Shne?derova V Ia Chirva A E Zemliakov 《Antibiotiki i khimioterapii͡a》1989,34(11):836-839
Production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) by macrophages of the spleen and peritoneal exudate of mice as well as cytotoxic factors (CFs) by murine splenocytes after in vitro activation was estimated. All the derivatives of muramyldipeptide (MDP) and glucosaminylmuramyldipeptide (GMDP) were able to induce production of TNF and CFs. In the presence of lipopolysaccharide (LPS), the effect was always higher. The response of the spleen macrophages to the effect of the preparations was higher than that of the peritoneal ones and ++non-fractionated splenocytes. GMDP and GMDP4 especially in the presence of LPS had the highest effect on induction of IL-1 by the murine peritoneal macrophages. On the contrary, MDP induced higher IL-1 synthesis by the spleen macrophages. The most active substances with respect to production of TNF, CFs and IL-1, i.e. MDP3 and GMDP4, might be recommended for immunotherapy of syngeneic tumors in animals. 相似文献
6.
I J Fidler W E Fogler E S Kleinerman I Saiki 《Journal of immunology (Baltimore, Md. : 1950)》1985,135(6):4289-4296
Highly purified human blood monocytes, isolated by continuous Percoll density gradients under endotoxin-free conditions, and mouse peritoneal exudate macrophages (PEM) were activated in vitro by the combination of muramyl dipeptide (MDP) and recombinant interferon-gamma (r-IFN-gamma) to become tumoricidal against their respective tumorigenic target cells. The activation of human monocytes or mouse PEM by free unencapsulated r-IFN-gamma and MDP was species specific: human r-IFN-gamma activated human blood monocytes to lyse allogeneic melanoma cells, but did not activate mouse PEM. Mouse r-IFN-gamma activated mouse PEM to lyse syngeneic melanoma cells, but did not activate cytotoxic properties in human monocytes. The encapsulation of either mouse or human r-IFN-gamma with MDP within the same liposome preparation produced synergistic activation of cytotoxic properties in both PEM and monocytes without apparent species specificity. The activation of tumoricidal properties in macrophages by r-IFN-gamma and MDP occurred as a consequence of intracellular interaction. We base this conclusion on the data showing that whereas free r-IFN-gamma and MDP did not activate macrophages pretreated with pronase, liposome-encapsulated r-IFN-gamma and MDP did. Moreover, the i.v. injection of liposomes containing human or mouse r-IFN-gamma and MDP produced in vivo activation of mouse alveolar macrophages. These data suggest that in contrast to activation with free r-IFN-gamma, which requires binding to macrophage surface receptors, the intracellular interaction of r-IFN-gamma, which produces tumoricidal activity in macrophages, is not species specific. 相似文献
7.
Semenov BF Zakharova NS Britsina MV Mertsalova NU Ozeretskovskaia MN Valiakina TI Komaleva RL Andronova TM Nesmeianov VA 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》2004,(6):31-36
As shown in this work, the synthetic immunomodulator glucosaminylmuramyldipeptide (GMDP) can be included into acellular pertussis vaccine (APV). The optimal doses of GMDP, ranging from 0.001 to 0.0001 microg, have been found. These doses enhance the protective activity of APV, especially its low-active doses. GMDP decrease the manifestations of toxic, anaphylactogenic and pyrogenic properties of APV, which may lead to the decrease of the antigenic load of APV on the body of the vaccines and thus to lessening the side-effects of vaccination. GMDP has been shown to considerably increase, in comparison with common pertussis vaccine and APV, the percentage of phagocytizing leukocytes by day 14. The immunization of mice with APV with and without GMDP in doses of 0.01 and 0.001 microg leads to a change in T-lymphocyte/B-lymphocyte ratio in the population of spleen lymphocytes. 相似文献
8.
Zakharova NS Agal'tsova SI Shmeleva EI Britsina MV Ozeretskovskaia MN Remova TN Bazhanova IG Mertsalova NU Ermolova EV 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》2003,(3):30-34
Toxic properties of acellular pertussis vaccine (APV) and morphological changes in white mice in response to intramuscular injection of APV (without or with immunomodulator glucosaminylmuramyl dipeptide-GMDP) were under study. APV used in these experiments was developed at the Mechnikov Research Institute for Vaccines and Sera (the Russian Acad. Med. Sci.) on the basis of Bordetella pertussis cultures in synthetic fluid culture media. In experiments on acute and chronic toxicity of APV (without GMDP) increased tissue immunity reactions in spleen, thymus, liver, lungs and intestinal wall was detected. There was no difference in immunomorphological reactions in mice receiving APV with different doses of GMDP, but some difference was observed in time dynamics of tissue immunity reactions. A small dose of GMDP should be preferred (0.0001 microgram) which results in gradual growth of tissue immunity reactions less pronounced toxic reactions caused be the APV injection. 相似文献
9.
Somesh D. Sharma Van Tsai James L. Krahenbuhl Jack S. Remington 《Cellular immunology》1981,62(1):101-109
The ability of muramyl dipeptide (MDP) and its structural analogs (des-MDP, abu-MDP, and des-abu-MDP) to influence mouse natural killer (NK) cells in two different strains of mice was examined. In CBA/J mice, administration of MDP by both intraperitoneal (ip) and intravenous (iv) routes enhanced splenic NK cell activity. Maximum augmentation of NK cell activity was observed 3 days after MDP treatment. NK cell activity was also stimulated upon in vitro culture of CBA/J mouse spleen cells with MDP. Only iv inoculation of MDP to C57BL/6 mice 7 days previously enhanced NK cell activity of spleen cells. Peritoneal NK cell activity was not affected in either strain of mice, regardless of the route of inoculation of MDP. Two structural analogs of MDP, abu-MDP and des-abu-MDP, enhanced peritoneal NK cell activity, whereas des-MDP had no effect when tested 3 days after ip treatment of CBA/J mice with these compounds. Peritoneal NK cell activity of C57BL/6 mice was not modulated by des-MDP, abu-MDP, or des-abu-MDP. A synergistic effect on peritoneal NK cell activity was observed in both CBA/J and C57BL/6 mice treated first with MDP and then with lipopolysaccharide (LPS) or Bacillus Calmette-Guerin (BCG). 相似文献
10.
Ermolova EV Britsina MV Ozeretskovskaia MN Shepeleva IB Zakharova NS 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》1999,(6):56-59
The influence of whole-cell and acellular pertussis vaccines, introduced both alone and in combination with N-acetylglucosaminylmuramyl-2-alanine-D-isoglutamine (GMDP) on the activity of two enzymes of peritoneal exudate macrophages (5'-nucleotidase and Na+K(+)-adenosine triphosphatase) was studied. The study revealed that both pertussis vaccines exhibited immunomodulating properties, these properties being most pronounced in whole-cell pertussis vaccine. The use of GMDP in combination with pertussis vaccines led to changes in the enzymatic activity of peritoneal exudate macrophages, which was indicative of a decrease in the immunomodulating action of pertussis preparations. 相似文献
11.
Muramyl dipeptide (MDP), a synthetic adjuvant, increased the primary response of CBA mice to sheep red blood cells (SRBC). In reconstituted irradiated recipients, cooperation between T and B lymphocytes was required for the expression of adjuvant activity and MDP increased the efficiency of SRBC-educated T cells. The role of T-derived lymphocytes in mediating the MDP adjuvant activity was also demonstrated in irradiated mice and in mice reconstituted with various splenic cellular types of donors which had received SRBC and MDP 24 hr earlier. In our experiments, the macrophage did not seem to be involved, since MDP did not increase the phagocytic capacity of peritoneal exudate cells and MDP- and SRBC-pretreated macrophages had no increased ability to induce an anti-SRBC immune response. These results demonstrate the importance of T lymphocytes as mediators of the adjuvant activity of MDP. 相似文献
12.
B B Fuks A I Shapoval I Grzhebin IM 《Biulleten' eksperimental'no? biologii i meditsiny》1991,112(7):78-80
We investigated the phenomenon of increased sensitivity of tumor-bearing mice to endotoxin shock. I/V administration of sera from tumor (EL-4, B16, R815, MOPC-315) bearers or tumoral culture media into intact mice caused the increased sensitivity to lethal action of LPS plus GMDP. Production of TNF in above mice was also significantly increased under the influence of LPS plus GMDP. Sensitivity induced factors in tumor bearing mice sera have mol. weight more than 50 kDa. This action was partially abolished by indomethacin. 相似文献
13.
M V Britsina I B Shepeleva A P Baturo S I Elkina N G Kalina T M Andronova E V Ermolova N S Zakharova V T Ivanov T V Sokolova 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》1992,(5-6):43-45
As revealed in animal experiments, glucosaminylmuramyl dipeptide (GMDP), the synthetic analog of muramyl dipeptide, when introduced intraperitoneally in a single injection or orally, exhibits adjuvant activity with respect to Citrobacter 0-antigens, Shigella flexneri and enhances the protective properties of dysentery and pertussis vaccines. The stimulating properties of GMDP depend on its dose, the route of its administration, the time elapsed after its administration, its ratio to the concomitant doses of bacterial antigens and to the dose of the virulent culture used for challenge. 相似文献
14.
15.
MurNAc-l-Ala-d-isoGln (N-acetylmuramyl-l-alanyl-d-isoglutamine, MDP), a synthetic compound, acts as an adjuvant on the humoral immune response and on the T cell-mediated immune response. In this report, we attempted to directly demonstrate the initial target cells of MDP for its adjuvant activity in vitro by using cell separation procedures.It was demonstrated that MDP enhanced the immune response following direct interaction with antigen-stimulated T and B lymphocytes, but nonstimulated lymphocytes, shortly after triggering by antigen, and that there was no macrophage requirement for MDP to elicite the adjuvant action in the primary anti-SRBC PFC response in vitro. It has also been demonstrated that the adjuvant activity of MDP is due to an enhancing effect which is different from the possible mitogenic activity to spleen cells and MDP replaces neither a function of macrophages, which is substituted by 2-mercaptoethanol nor a helper function of T cells. 相似文献
16.
N G Kalina S I Elkina V V Sergeev 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》1984,(12):107-110
The stimulating influence of glucose-containing muramyldipeptide (GMDP) on the nonspecific resistance of mice was shown to depend on the features of the pathogenesis of the infection. Thus, the intraperitoneal injection of GMDP increased the survival rate of mice infected with Escherichia coli, but had no stimulating effect on the resistance of the animals to Salmonella typhimurium natural infection in whose pathogenesis macrophages played an essential role. Experiments demonstrated that GMDP was capable of enhancing the ingestive function of macrophages, but did not increase their bactericidal activity with respect to this infection. 相似文献
17.
Vladimir I Slesarev Rita Ellithorpe Todor Dimitroff 《Cancer immunology, immunotherapy : CII》1998,15(1):37-43
The current study was designed to investigate direct inhibitory effects of N-acetylglucosaminyl-muramyldipeptide (GMDP) over
the cytotoxic nature of TNF-α. A lactate dehydrogenase (LDH) assay of the inhibition of TNF-α cytotoxicity was donein vitro on the following cell lines: A549 (human lung carcinoma cells), A431 (human breast cancer cells) and L929 (mouse breast cancer
cells). In a double-blind placebo-controlled trial, cancer patients with an elevated activity of all five LDH isoensymes were
randomized to receive either a GMDP solution or a placebo; 63 patients were evaluated every third day for the mean daily number
of episodes of nausea or vomiting, changes in clinical status, cell blood count and blood chemistry. A 95% inhibition of LDH
release was noticed on A549 cells. Other cell lines were less sensitive to GMDP, with an observed 72% dose-dependent reduction
in LDH activity.In vivo, LDH activity was decreased by 41% (+/−4%) (mean +/−SD) in all 21 subjects who were given 0.5–1.0 mg of GMDP daily. A lowering
of LDH activity by 73.4% (+/−4%) was observed in 23 patients who received GMDP at a dosage of 1.5 mg/kg daily. Correspondingly,
a 10% (+/−2%) increase in LDH activity was noticed in 19 patients who were given a placebo (P<0.01). During the follow-up period, the overall clinical condition of all patients treated with GMDP was improved. No side
effects were observed. In nine patients who experienced nausea from tumor toxicity before treatment, the symptom subsided.
In parallel, an extremely beneficial effect on lipids metabolism was noticed in all patients with elevated cholesterol and
trigliceride levels. A dietary supplementation of GMDP has been shown to reduce systemic TNF-α cytotoxicity during tumor shock. 相似文献
18.
Akhmatova NK Semenova IB Donenko FV Kiselevskiĭ MV Kurbatova EA Egorova NB 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》2006,(6):35-40
Effect of immunomodulators for microbial origin on innate immunity and antitumor system was continued to study. Immunomodificator Immunovac VP-4, purified staphylococcal toxoid and glucosaminyl muramyl dipeptide (GMDP) equally enhanced cytotoxicity of mononuclear leukocytes of peripheral blood of healthy donors. Index of cytotoxicity was 2.78, 2.77 and 2.70 respectively. Reduced metastatic progression of Lewis lung carcinoma in mice was observed after Immunovac VP-4 and GMDP administration. Effectiveness was seen when preparations administered according to schedules including their administration before implantation of the tumor. If preparations were administered number of metastases reduced in 4.4-5.6 times and size of metastases reduced in 7-10 times. Interplay between antitumor activity of studied immunomodulators and cytotoxic activity of NK-cells, which are base effectors of antitumor immune response, are discussed. 相似文献
19.
Direct augmentation of cytolytic activity of tumor-derived macrophages and macrophage cell lines by muramyl dipeptide. 总被引:7,自引:0,他引:7
Macrophages derived from MSV-induced tumors and several macrophage cell lines showed direct cytolytic activity in an 18-hr 51Cr release assay against tumor target cells. The cytolytic activity of these macrophages was augmented by the addition of muramyl dipeptide (MDP) to the cytotoxicity assay, an effect similar to that observed with bacterial lipopolysaccharide. The stimulation of macrophage-mediated cytotoxicity by MDP appeared to be under genetic control since macrophages from BALB/c mice were augmented with MDP while those from C57BL/6 animals were not. MDP appears to act directly on the macrophage without the participation of any other cell type, since MDP increased the activity of the macrophage cell lines. 相似文献
20.
Nanne Bloksma Frans M. A. Hofhuis Jan M. N. Willers 《Cancer immunology, immunotherapy : CII》1985,19(3):205-210
Summary The potentiation of endotoxin-induced necrosis and regression of solid syngeneic Meth A tumors in mice previously observed following administration of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) was investigated further by use of various muramyl peptide analogues and two unrelated synthetic adjuvants, viz. the pluronic polyol L121 and dimethyldioctadecylammonium bromide (DDA) instead of MDP. All agents were administered in aqueous solution by the IV route. None of the muramyl peptide analogues nor L121 or DDA had any strong antitumor action of their own. Two 6-O-acylated muramyl peptides (L2-MDP and B30-MDP) and muramyl dipeptide stearoyllysine [MDP-Lys (L18)] clearly potentiated endotoxin-induced necrosis and regression. In contrast, MDP with L- instead of D-isoglutamine was completely inactive. Optimal activity of B30-MDP and MDP-Lys (L18) was only achieved by adding of suitable amounts of a nonionic surfactant. L121 and DDA could not replace muramyl peptides as potentiating agent. The combination of endotoxin, MDP, and L121 caused complete tumor regression in all mice, but was highly toxic.On the basis of the data in the literature on the biological response-modifying activities of the agents used it is concluded that the potentiating activity of muramyl peptides cannot yet be related to their immunoadjuvant action or their capacity to activate macrophages or to enhance nonspecific bacterial resistance.The work described in this paper was supported by grant UUKC 82-15 from the Koningin Wilhelmina Fonds, The Netherlands Cancer Organization 相似文献