Activation of macrophages for enhanced release of superoxide anion and greater killing of Candida albicans by injection of muramyl dipeptide.

Cummings, Nancy P.; Pabst, Michael J.; Johnston, R B

doi:10.1084/jem.152.6.1659

Cited by 110 publications

(52 citation statements)

References 30 publications

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“…The experimental design varied with respect to different ratios of infection, exposure of C. albicans to one of the antifungal agents prior to macrophage ingestion, and exposure to the antifungal agents alone or in combination. It is known that resident peritoneal macrophages are unable to kill C. albicans during incubation in vitro and are even unable to prevent intracellular germ tube formation (2,3,7,24,38). As a consequence, the antifungal effect on intracellular C. albicans could be investigated without interference from the direct fungistatic or fungicidal effects of the macrophages themselves.…”

Section: Discussionmentioning

confidence: 99%

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Etten

Rhee

Kampen

et al. 1991

Antimicrob Agents Chemother

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The effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans were studied. With respect to the extracellular growth of C. albicans, antifungal activity was measured in terms of MICs and minimal fungicidal concentrations as well as by determination of the concentration that effectively killed (>99.9%) C. albicans in the absence or presence (amphotericin B only) of serum. Amphotericin B was highly active in terms of killing, even at an increased inoculum size. In the presence of serum, amphotericin B activity was substantially reduced. For fluconazole, activity was restricted to inhibition of fungal growth, even after the inoculum size was reduced. With respect to the intracellular growth of C. albicans, antifungal activity was measured by using monolayers of murine peritoneal macrophages infected with C. albicans and was measured in terms of inhibition of germ tube formation as well'as effective killing (>99%) of C. albicans. Amphotericin B was highly active against C. albicans. At an increased ratio of infection, amphotericin B activity was slightly reduced. Fluconazole had no antifungal activity. Neither a reduction in the ratio of infection nor exposure of C. albicans to fluconaz'ole prior to macrophage ingestion resulted in activity against intracellular C. albicans by fluconazole. Previous exposure of C. albicans to amphotericin B resulted in increased intracellular activity of amphotericin B. The. intracellular antifungal activity of the combination of fluconazole with amphotericin B was les than that of amphotericin B alone. Amphotericin B showed fungicidal activity against C. albicans growing both extracellularly and intracellularly, whereas fluconazole inhibited growth only of extracellular C. albicans. A slight antagonistic effect between fluconazole and aiflphotericin B was found with respect to intracellular as well as extracellular C. albicans.Deep-seated candidal infections are an important cause of morbidity and mortality in immunocompromised patients (15,21,22). The current drug of choice for most systemic mycoses is still amphotericin B (AmB), but its use is restricted by a variety of toxic side effects (6,13,15,21,22). Consequently, there is a need for effective and less toxic drugs for the treatment of patients with these infections. One of these antifungal agents is the triazole fluconazole (Flu) (4,10,14,33,34,41). In vivo experimental studies suggested that Flu is active against disseminated candidiasis (8,9,29,31,32,35,37). Recently, the antifungal efficacy of Flu was demonstrated in persistently granulocytopenic rabbits when it was used for prevention or early treatment (39,40). Little is still known, however, on the role of Flu in the treatment of systemic candidiasis in immunocompromised patients. Since the host defense mechanisms in these patients are severely impaired, the intrinsic antifungal activity of the antifungal agent is of great importance for effective treatment. Unfortunately, standardized in vitro methods for assessment of ...

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Section: Discussionmentioning

confidence: 99%

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Etten

Rhee

Kampen

et al. 1991

Antimicrob Agents Chemother

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“…An FITC-labeled preparation of C. albicans was prepared as in [25,26]. Control or toxin-treated neutrophils (0.9 ml, 1 x 10' cells/ml) were mixed with 0.9 ml micro-orga~sms (1 x 10' organisms/ml) and 0.2 ml heat-treated human serum.…”

Section: Phagocytosis Of C Albicansmentioning

confidence: 99%

A step sensitive to pertussis toxin and phorbol ester in human neutrophils regulates chemotaxis and capping but not phagocytosis

Lad¹,

Olson²,

Grewal³

1986

FEBS Letters

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Treatment of human neutrophils with pertussis toxin (PT) abolishes chemotaxis in response to either platelet-activating factor (PAF) or f-Met-Leu-Phe (FMLP), and capping induced via the concanavalin A (Con A) receptor. These functional effects are accompanied by the inhibition of calcium mobilization by PAF, FMLP and Con A. The agent phorbol 12-myristate-13-acetate (PMA) also inhibits chemotaxis and capping as well as calcium mobilization by these receptors. In sharp contrast, neither PT, cholera toxin (CT), nor PMA, inhibits the phagocytosis of non-opsonized and opsonized Candida albicans, sheep erythrocytes or fluorescent latex beads. Our results suggest that receptor-initiated chemotaxis and capping involve a step that is sensitive to PT and PMA, and that phagocytosis is not regulated in a similar fashion.

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“…In sys temic candidal infection in experimental animals, these sub stances were able to improve survival [6][7][8], but because of their toxicity they have not been appealing as a therapy in humans. These immunomodulatory drugs are able to induce synthesis and secretion of interleukin 1 (IL1), a family of cytokines mediating the acute-phase response [9].…”

Section: Introductionmentioning

confidence: 99%

Protection of neutropenic mice from lethal Candida albicans infection by recombinant interleukin 1

Wout¹,

Meer

Barza

et al. 1988

Eur J Immunol

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Natural and synthetic immunomodulators that increase nonspecific resistance to infection are also known to induce interleukin 1 (IL1) production. Previous studies have demonstrated a protective effect of recombinant human IL 1(3 against death from infection caused by Pseudomonas aeruginosa. In the present study we investi gated the effect of IL 1(3 or IL la on the survival of neutropenic mice with a lethal Candida albicans infection. Mice with cyclophosphamide-induced neutropenia were injected with 3 x 10D C. albicans i.v. When 80 ng IL1(3 was given as a single i.p. injection 24 h before the infection, survival compared to that in control animals was as follows: 100% vs. 97% at 24 h, 83% vs. 70% at 48 h and 70% vs. 23% at 72 h after the infection (p<0.01). The effect of IL1 was also apparent when it was given Zi h before or 6 h after the infection. The results obtained with 80 ng IL la given at 24 h before infection were similar to that obtained with IL1(3. The numbers of Candida cultured from the blood, liver, spleen, and kidney were not significantly different in ILip-treated and control animals. Passive transfer of serum obtained from mice pretreated with IL 1 to recipient mice did not provide protection against a subsequent lethal candidal infection. In conclusion, the present study demonstrates that IL ip and IL la prolong survival in neutropenic mice with a lethal C. albicans infection.

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Activation of macrophages for enhanced release of superoxide anion and greater killing of Candida albicans by injection of muramyl dipeptide.

Cited by 110 publications

References 30 publications

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

Effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans

A step sensitive to pertussis toxin and phorbol ester in human neutrophils regulates chemotaxis and capping but not phagocytosis

Protection of neutropenic mice from lethal Candida albicans infection by recombinant interleukin 1

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