Stimulation of Resistance of Immunocompromised Mice by a Muramyl Dipeptide Analog

Osada, Yasuaki; Mitsuyama, Masao; Matsumoto, Kensuke; Une, Tsutomu; Otani, Tomoyuki; Ogawa, Hidemasa; Nomoto, Kikuo

doi:10.1128/iai.37.3.1285-1288.1982

Cited by 27 publications

(6 citation statements)

References 17 publications

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“…Because WAM025 contains protein, N-acetylglucosamine, and phosphorus, constituting phosphomannan-protein complex(es) (2,10,15), while WNM consists of a simple polysaccharide with a very small amount of protein, it is suggested that the other components of WAM025 other than the mannan part may have an important role in evoking the protection against C. albicans infection in mice. WAM-025 should thus be a useful immunostimulant in the host-defense system of infected and tumor-bearing hosts, similar to several immunopotentiators (16,(18)(19)(20)23). The possible collaboration of other factors with infection-protecting activity and the effect of post-treatment with WAM025 on C. albicans infection remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Acidic Mannan Fraction of Bakers' Yeast on Experimental Candidiasis in Mice

Okawa

Suzuki

Kobayashi

et al. 1986

Microbiology and Immunology

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An acidic fraction of bakers' yeast mannan, WAMO25, showed a significant protective effect against Candida albicans infection in mice, but a neutral fraction of the same bakers' yeast mannan, WNM, did not exhibit this effect. Moreover, pretreatment with WAM025 resulted in a marked reduction of proliferation of C. albicans cells in the organs of the infected mice. We investigated the stimulative effect of these mannan fractions on the function of mouse peritoneal phagocytes, and found that mice administered WAMO25 showed a greater increase in the number of peritoneal exudate cells, macrophages and polymorphonuclear leucocytes (PMN), than the mice treated with WNM, especially in the proportion of PMN. Peritoneal phagocytes, PMN and macrophages obtained from WAMO25-treated mice showed marked candidacidal activity. Of the phagocytes, PMN were responsible for the larger part of the candidacidal activity. The myeloperoxidase activities of PMN and macrophages in WAM025-treated PEC were greater than in untreated macrophages. The myeloperoxidase activity of WAM025-treated PMN was significantly greater than that of WAM025-treated macrophages. This activity paralleled the active oxygen-releasing activity of the phagocytes. On the other hand, the phagocytic activity of phagocytes from mice administered WNM or WAM025 for C. albicans cells was identical to that of untreated phagocytes. WAM025 seems to cause enhance elimination of the pathogen from mice, by increasing the number and candidacidal activity of phagocytic cells.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Acidic Mannan Fraction of Bakers' Yeast on Experimental Candidiasis in Mice

Okawa

Suzuki

Kobayashi

et al. 1986

Microbiology and Immunology

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“…The bands of C3 protein in sera of mice with PBS and those from mice with the adjuvant were illustrated on the upper and lower side of each agarose slit, respectively. complement systems might be involved in the resistance mechanisms of animals to microbial infections, which are stimulated by MDPs (6,14,15,22,23,25). To clarify its involvement in the enhancement of defense by MDP-Lys(L18) against microbial infections in mice, a quantitative and qualitative examination was made of serum C3 in mice treated with or without the adjuvant.…”

Section: Discussionmentioning

confidence: 99%

“…Muramyl dipeptide (MDP) and some of its analogs (MDPs) have been reported to enhance the nonspecific resistance of animals to microbial infections (6,14,15,22,23,25). Osada et al have recently found that polymorphonuclear leukocytes (PMNs) were activated in vitro and in vivo by an MDP analog, Nn-(N-acetyl-muramyl-L-alanyl-D-isoglutamine)-N'-stearoyl-Llysine [MDP-Lys(L18)] (24).…”

mentioning

confidence: 99%

Stimulation of complement production in mice by N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutamine)-N epsilon-stearoyl-L-lysine

Endo¹,

Okuda²,

Osada³

et al. 1983

Infect Immun

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N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutamine)-N epsilon-stearoyl-L-lysine, a synthetic muramyl dipeptide analog, stimulated the production of the third component of complement (C3) in mice. The serum concentration of C3 was elevated significantly by subcutaneous treatment with a single dose (10 to 100 micrograms per mouse) of the adjuvant 24 h before assay of the serum. Thereafter, the concentration decreased gradually with time and returned to the normal level on day 4 to 5. Immunoelectrophoretic analysis of the serum revealed that the decrease in serum C3 could not be accounted for by the cleavage to C3a and C3b. By intermittent treatment with the adjuvant on every fifth day, a significant increase in serum C3 was repeated. However, no continuous retention of the serum level of C3 was established even during continuous treatment with the adjuvant once a day for 10 consecutive days. Instead, in this case, the level of C3 increased repeatedly at almost 5-day intervals.

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“…The two molecules were also found to effectively limit infection of the opportunistic pathogen Cornyebacterium kutscheri in a cortisone‐mediated model of immunosuppression . Similarly, 6‐ O ‐stearoyl‐MDP enhanced host resistance against both E. coli and C. albicans infection in immunocompromised mice treated with either X‐ray irradiation or cyclophosphamide and limited P. aeruginosa ‐associated pneumonia in immunocompromised guinea pigs . Nonspecific protection was observed as well during viral infections.…”

Section: Peptidoglycan Metabolites and Adjuvanticitymentioning

confidence: 93%

Translation of peptidoglycan metabolites into immunotherapeutics

et al. 2019

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The discovery of defined peptidoglycan metabolites that activate host immunity and their specific receptors has revealed fundamental insights into host–microbe recognition and afforded new opportunities for therapeutic development against infection and cancer. In this review, we summarise the discovery of two key peptidoglycan metabolites, γ‐d‐glutamyl‐meso‐diaminopimelic acid (iE‐DAP) and muramyl dipeptide and their respective receptors, Nod1 and Nod2, and review progress towards translating these findings into therapeutic agents. Notably, synthetic derivatives of peptidoglycan metabolites have already yielded approved drugs for chemotherapy‐induced leukopenia and paediatric osteosarcoma; however, the broad effects of peptidoglycan metabolites on host immunity suggest additional translational opportunities for new therapeutics towards other cancers, microbial infections and inflammatory diseases.

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Stimulation of Resistance of Immunocompromised Mice by a Muramyl Dipeptide Analog

Abstract: L18-MDP(Ala), a synthetic derivative of muramyl dipeptide, enhanced resistance against Escherichia coli and Candida albicans infections in aged mice and younger adult mice whose defense mechanism(s) had been depressed by X-ray irradiation or by treatment with cyclophosphamide.

Cited by 27 publications

References 17 publications

Protective Effect of Acidic Mannan Fraction of Bakers' Yeast on Experimental Candidiasis in Mice

Protective Effect of Acidic Mannan Fraction of Bakers' Yeast on Experimental Candidiasis in Mice

Stimulation of complement production in mice by N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutamine)-N epsilon-stearoyl-L-lysine

Translation of peptidoglycan metabolites into immunotherapeutics

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