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Biomedical subjects

F Bistoni

Publications and source records attributed to F Bistoni.

At least 163 records · Page 9Linked to original sources
PubMed1990

Presence of a plant-like glyoxalase II in Candida albicans.

Glyoxalase II from Candida albicans was purified by affinity chromatography on S-carbobenzoxyglutathione-Affi Gel 10. The enzyme was characterized and compared with the glyoxalases II from animal and plant sources. The relative molecular mass is 29 kDa, and the isoelectric point (pI) is 6.0. The acidic pI value appears to be typical for plant glyoxalase II, in contrast to the uniformly basic glyoxalase II pI values from animals. S-D-Lactoylglutathione and S-acetoacetylglutathione are the best substrates, and S-carbobenzoxyglutathione is the best inhibitor of the yeast enzyme. Glutathione derivatives with a thioether bond are not inhibitory. Glyoxalase II from Candida albicans is compared either with animal and plant enzymes.

Animals↗
PubMed1989

Protective immunity induced by low-virulence Candida albicans: cytokine production in the development of the anti-infectious state.

A low-virulence, agerminative strain of Candida albicans (PCA-2) is able to confer a high degree of nonspecific protection against subsequent challenge with highly virulent microorganisms in mice. In an attempt to better define the effect of PCA-2 vaccination on the immune system and the nature of the mechanisms involved in this protective state, we evaluated the pattern and kinetics of production of selected cytokines in PCA-2-treated mice. Thus, granulocyte/monocyte colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 1 (IL-1) were measured in the sera and spleen cell supernatants of vaccinated mice. In both cases, high levels of CSF, TNF, IL-1, and IFN were found 6 hr after PCA-2 infection and persisted for many days. There was always a correlation between the ability of PCA-2 to induce antimicrobial protection in vivo and its ability to cause cytokine production in vitro. Supernatants of splenocyte cultures from PCA-2-infected animals possessed macrophage-activating activity, as measured in microbiological assays. These data suggest an important involvement of cytokines in the nonspecific anti-infectious immunity induced by PCA-2, and also suggest a crucial role for IL-1 as an endogenous adjuvant in the initiation of the immune response to PCA-2.

Amphotericin B↗
PubMed1989

Identification of a trypanocidal factor against Trypanosoma equiperdum in normal human serum.

Normal human serum (HS) contains trypanolytic activity and agglutinins to Trypanosoma equiperdum, while such activities are not found in sera from a range of animals susceptible to infection. HS given to T. equiperdum-infected mice caused a rapid decrease in the number of circulating trypanosomes and protection from lethal infection. Trypanolytic activity of human serum was found to be associated, after DEAE chromatography and Sephadex G-200 gel filtration, with the fraction containing 19S antibodies. Immunofluorescence assays confirmed a binding of human IgM and C1q complement component onto the surface of T. equiperdum. Anti-T. equiperdum activity of HS was specifically directed to T. equiperdum surface components and not to some mouse serum components adsorbed on parasites during the growth in the host, because HS adsorbed in vivo in CD-1 mice retained full protective and agglutinating properties. Trypanocidal activity appears in human serum about the 7th month after birth and persists until late in life. On the contrary, human purified high-density lipoprotein had no significant in vitro or in vivo trypanocidal activity. In conclusion, strong natural anti-T. equiperdum activity in human serum was mainly mediated by natural antibodies of the IgM class. The presence of natural IgM active against T. equiperdum in HS could represent one of the natural mechanisms of resistance of refractory hosts against trypanosome infections. This phenomenon provides further evidence that host specificity of trypanosomes may be partly conditioned by the presence of natural antibodies.

Agglutination Tests↗
PubMed1989

Immunosuppressive effect of cyclosporin A on resistance to systemic infection with Candida albicans.

We studied the influence of cyclosporin-A (Cy-A) on resistance of mice to systemic infection with Candida albicans. Cy-A clearly inhibited resistance to C. albicans. The effect was dose-dependent and time and route of administration of the drug were important. This immunodepressive effect was due, at least in part, to an impairment of polymorphonuclear leucocyte (PMNL) candidacidal activity, as demonstrated in vitro by a reduction of phagocytic and cytotoxic activity and in vivo by protection when PMNL from untreated mice were transferred into cyclophosphamide-treated hosts challenged with C. albicans. The decreased activity of PMNL could be partly restored by adoptive transfer of normal T-lymphocytes into Cy-A-treated mice, as well as by exposure of PMNL to gamma-interferon (IFN-gamma) in vitro.

Animals↗
PubMed1989

Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice.

Protective immunity to lethal Candida albicans challenge in vivo and activation of splenic macrophages with highly candidacidal activity in vitro were detected in mice infected with low-virulence agerminative yeast cells of the variant strain PCA-2, at a time when a strong delayed-type hypersensitivity (DTH) reaction to C. albicans occurred in the footpads of PCA-2-treated mice. The DTH reaction was transferable with spleen cell populations from these animals, and enrichment of splenic lymphocytes in L3T4+ cells significantly increased the footpad swelling. The reactivity transferred by L3T4+ cells was a radiosensitive (2,500 rads in vitro) phenomenon that required collaboration with radioresistant, silica-sensitive syngeneic cells in the host and was inhibited by treatment of recipient mice with antibodies to the L3T4 antigen or murine gamma interferon. In vitro, the PCA-2-immune L3T4+ cells produced various lymphokine activities upon incubation with C. albicans, including gamma interferon and granulocyte-macrophage colony-stimulating factor. Anti-L3T4 monoclonal antibody treatment of PCA-2-infected mice significantly impaired their footpad reaction and resistance to C. albicans, as shown by increased recovery of yeast cells from the kidneys of anti-L3T4-treated mice. These results suggested that the mechanisms of anti-Candida resistance induced by PCA-2 may involve specific induction of a DTH response mediated by inflammatory L3T4+ T cells and lymphokine-activated phagocytic effectors. However, the survival rate of the PCA-2-immune mice challenged with C. albicans was not significantly modified by administration of the anti-L3T4 antibody, thus allowing for the conclusion that compensatory mechanisms lead to considerable anti-Candida resistance when the activity of L3T4+ cells is deficient.

Animals↗
PubMed1989

Selective inhibition of cytokine-induced lysozyme activity by tetanus toxin in the GG2EE macrophage cell line.

This study was designed to evaluate the effects of tetanus toxin (TT) on lysozyme (LZM) activity by the GG2EE macrophage cell line. GG2EE cells spontaneously produced low amounts of LZM, which were mostly secreted into the culture medium. Upon treatment with various cytokines, GG2EE cells exhibited altered LZM activity. In particular, exposure of GG2EE cells to alpha/beta interferon (IFN-alpha/beta) reduced LZM activity, as opposed to treatment with gamma interferon (IFN-gamma) or colony-stimulating factor 1, which potentiated LZM activity. Spontaneous LZM activity of GG2EE cells was not susceptible to TT action; in contrast, when IFN-gamma- or colony-stimulating factor 1-susceptible cells were treated with TT, a significant reduction on LZM activity was observed. The TT inhibitory effect was dose dependent and manifested only after a 6-h incubation of GG2EE cells with TT. Treatment of GG2EE cells with heat-inactivated TT as well as Ibc- and B-IIb-TT-derived fragments was found to be ineffective, while pretreatment with B-IIb- but not with Ibc-TT-derived fragment abrogated the TT effect. Overall, these data indicate the existence of a specific TT-GG2EE cell interaction, leading to selective inhibition of cytokine-induced LZM activity.

Animals↗
PubMed1989

Modulation of anti-Candida activity of human alveolar macrophages by interferon-gamma or interleukin-1-alpha.

The fungicidal and bactericidal activities of human alveolar macrophages (AM) and peripheral blood monocytes (PBM) from 18 healthy volunteers were evaluated. The results showed that AM were able to phagocytize and kill Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. However, killing of the bacteria was already complete in 2 h, whereas killing of Candida required 4 to 6 h despite an early phagocytosis of yeast cells. The fungicidal activity of freshly collected AM and PBM was also tested after effector cell exposure to interferon-gamma (IFN-gamma), interleukin-1-alpha (IL-1 alpha), endotoxin lipopolysaccharide (LPS), or interleukin 2 (IL-2). It was found that treatment with IFN-gamma, IL-1 alpha, or LPS significantly augmented macrophage and PBM candidacidal activity, whereas the addition of IL-2 was ineffective. We also evaluated killing of C. albicans by AM cultured in vitro for different times. While phagocytosis was apparently unaffected, the candidacidal activity progressively decreased over the in vitro culture period, an effect that was largely reversed by cell exposure to IFN-gamma, IL-1 alpha, or LPS. In an experimental model in which mice infected with an agerminative C. albicans strain (PCA-2) resisted lethal microbial challenge, freshly harvested AM showed increased cytotoxic activity to Aspergillus fumigatus in vitro as well as enhanced IL-1 production. In conclusion, present data confirm the crucial role of AM in the surveillance of bacterial and fungal infections and indicate that treatment of these cells with IFN-gamma or IL-1 alpha is able to enhance their antimicrobial capability.

Adult↗
PubMed1989

Sarcoidosis: an alveolar macrophage disease?

The Authors focus on new functions of alveolar macrophages (AM) from patients with active pulmonary sarcoidosis. They show that sarcoid AM present a candidacidal activity higher than normal controls, probably due to an enhanced phagocytic efficiency. Furthermore, after LPS stimulation cultured sarcoid AM secrete larger amount of interleukin 1 (IL-1) and of tumor necrosis factor (TNF) than normal controls. In conclusion, a new key role is emerging for sarcoid AM: not only an antigen-presenting cell, but a cell with a great primitive potential in modulating the inflammatory process.

Bronchoalveolar Lavage Fluid↗
PubMed1988

Microbial flora of surface versus core tonsillar cultures in recurrent tonsillitis in children.

Surface and 'core' tonsillar specimens were collected from 60 children, between 2 and 14 years of age, suffering from recurrent tonsillitis, in order to establish the reliability of surface tonsillar swabbing technique and to define the most frequently involved aerobic and anaerobic microorganisms. From the qualitative point of view, the same mixed aerobic and anaerobic flora were obtained in both samples thus demonstrating the reliability of the surface swabbing technique. From the quantitative point of view, 187 microorganisms, 129 (69.2%) aerobes and 58 (30.8%) anaerobes were isolated from surface cultures while 184, 109 (59.2%) aerobes and 75 (40.8%) anaerobes from the core cultures, thus demonstrating a greater number of anaerobes in the core of the tonsil. The most common isolated aerobic microorganisms were the alpha- and beta-hemolytic Streptococci, the Neisseriae and the Staphylococcus aureus; the predominant anaerobic ones were the Fusobacterium nucleatum, the Bacteroides sp. and the Veillonella parvula. The isolated staphylococcus aureus and the bacteroides sp. were all beta-lactamase producers.

Adolescent↗
PubMed1988

Immunomodulation by a low-virulence, agerminative variant of Candida albicans. Further evidence for macrophage activation as one of the effector mechanisms of nonspecific anti-infectious protection.

Systemic infection of mice with a Candida albicans strain (PCA-2) incapable of yeast-mycelial conversion is known to activate host macrophages and confer protection against subsequent challenge with highly pathogenic cells of the same species or by other micro-organisms. In an attempt to define the relative contributions of different immune components to the protection mediated by PCA-2, we evaluated the effect of manipulations known to selectively deplete immune functions. By means of cytostatic drug or silica induced toxicity, it was possible to demonstrate that no crucial role in protection is played by cytotoxic T lymphocytes or B cells, nor by PCA-2 induced granulocytosis alone. The cells responsible for this effect were dacarbazine-resistant silica-sensitive macrophages whose activity in vivo paralleled the in vitro expression of splenic candidacidal activity. Macrophage activation by PCA-2 and increased anti-Candida resistance did not result from an immunological response mediated by T-dependent effectors, as these effects could be reproduced in athymic mice.

Adjuvants, Immunologic↗
PubMed1988

Cell wall components of Candida albicans as immunomodulators: induction of natural killer and macrophage-mediated peritoneal cell cytotoxicity in mice by mannoprotein and glucan fractions.

Cell wall components from Candida albicans were compared to intact cells for their ability to induce natural cytotoxic immunoeffectors in the peritoneal cavity of mice. A soluble mannoprotein extract (MP) and an insoluble glucan fraction (GG) strongly stimulated the generation of peritoneal effectors capable of lysing YAC-1 and P-815 tumour cell lines in vitro. The anti-YAC-1 effectors were characterized as natural killer (NK) lymphocytes while the anti-P-815 effectors appeared to be activated macrophages. The activity of each fraction was typically dose-dependent and both fractions differed from whole cells in the kinetics of induction of cytotoxicity. However, the NK and macrophage effectors generated by these materials had similar functional and phenotypic properties, irrespective of the material used as inducer. No mannoprotein was detected in the insoluble glucan fraction GG. Hence, the immunoenhancing activity of GG could not be attributed to the presence of some MP or MP-like component. Mannan-rich fractions with low (less than 3%) protein content (M) or extracted by hot alkaline reagent (M-alk) were inactive as NK and macrophage inducers. Thus, the cell wall of C. albicans contains at least two distinct macromolecular complexes which mediate the induction in murine peritoneal exudates of cytotoxic effectors active against tumour cell lines.

Animals↗
PubMed1988

Immunomodulation by Candida albicans: crucial role of organ colonization and chronic infection with an attenuated agerminative strain of C. albicans for establishment of anti-infectious protection.

Intravenous inoculation of an attenuated agerminative strain of Candida albicans (PCA-2) of low virulence, but not of two other species of Candida of low virulence (C. parapsilosis and C. viswanathii) into CD2F1 mice conferred protection against the highly virulent microbes C. albicans CA-6, Staphylococcus aureus and Aspergillus fumigatus. To provide protection, a definite inoculum size (10(6) cells per mouse) resulting in organ colonization and establishment of a long-lasting chronic infection with PCA-2 was needed. An inoculum of 10(5) cells gave rise to transient kidney colonization whereas inocula greater than 10(6) cells led to acute septicaemia and eventual death. Chronic infection of mice following inoculation of 10(6) PCA-2 cells was accompanied by detectable mannoprotein antigen levels in the serum (30-70 ng ml-1) while specific antibodies did not appear until 14 d after inoculation, at which time low antimannan antibody was present (ELISA titre 1:40-1:80). Chronic infection was characterized by the presence in the kidneys of 2-3 x 10(6) c.f.u. of PCA-2 for at least 40 d after inoculation. Pharmacological modulation of the host through administration of either an anti-Candida drug, amphotericin B, or an immunosuppressive agent, cyclophosphamide, strongly supported the premise that the anti-infectious state conferred by PCA-2 'immunization' correlated with the maintenance of a sufficient number of PCA-2 in vivo. Protection was 'switched on' when 2-3 x 10(5) cells were present in the kidneys. It was maximal at a kidney count of 2-3 x 10(6) c.f.u. of PCA-2, and promptly declined when the number of PCA-2 cells in the kidney fell below 2 x 10(5). Mice chronically infected with PCA-2 had splenic macrophages with pronounced candidacidal activity in vitro. Modulation of the growth of PCA-2 in vivo, which determined activation or deactivation of the protective state, was paralleled by a similar modulation in macrophage activation, showing that in all cases resistance to virulent organisms persisted as long as macrophage activation was present. The results demonstrate that a critical in vivo antigenic load is crucial for the occurrence of resistance to infection and suggests that macrophages could be involved in this protection.

Adjuvants, Immunologic↗
PubMed1987

Cell wall of Candida albicans and host response.

Modulation in chemistry and organization of cell wall macromolecules play decisive roles in the morphogenic processes and virulence of Candida albicans. Cell wall components also have a diversified range of effects on the host's immune system, including immunopotentiating or immunodepressing activities. Mannan, mannan-protein, and glucan fractions have been especially studied in this context. In in vitro cultured human peripheral blood mononuclear cells, a mannan-protein fraction (GMP) from the cell wall of the yeast form acted as a strong antigenic activator by stimulating lymphokine production and lymphocyte proliferation. Cytolytic effectors active against several tumor targets were also generated. In the mouse, GMP was a strong inducer of natural killer lymphocytes. Other cell wall components, mostly the insoluble beta-glucan, modulated the activity of macrophages and monocyte precursors. Some of the immunomodulating properties of artificially extracted components were shared, even with greater potency, by antigens which were released from C. albicans during its growth and hyphal morphogenesis. Altogether, the range of the immunoresponses elicited and the intensity of the observed effects are such as to individuate in this human indigenous fungus a microorganism capable of profoundly affecting the host's immune system.

Animals↗