The phagocytosis and transforming activity of crystalline metal sulfide particles are related to their negative surface charge

Abbracchio, Maria P.; Heck, J. Daniel; Costa, Max

doi:10.1093/carcin/3.2.175

Cited by 57 publications

(31 citation statements)

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“…The synthesis procedure used differed from that ofAbbracchio et al (10) only in our use of an acetate buffered medium. Both the cytotoxicity (LD50 = 4.1 pg Ni/ml) and mutagenicity of "amorphous NiS" suggest that crystalline NiS2 is a sulfide of high cytotoxic and genotoxic potency.…”

Section: Discussionmentioning

confidence: 99%

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Toxicity, uptake, and mutagenicity of particulate and soluble nickel compounds.

Fletcher

Rossetto

Turnbull

et al. 1994

Environ Health Perspect

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Toxicity testing in AS52 cells (24-hr exposures) gave LC50 values of 2 to 130 pg Ni/ml for particulate nickel compounds and 45 to 60 pg Ni/ml for water-soluble salts (NiCI2, NiSO4, Ni(CH3COO)2). The Ni(OH)2, NiCO3, and sulfides (Ni3S2, Ni7S6, "amorphous NiS") exhibited similar toxicities (LC50's of 2 to 8 pg Ni/ml), while three nickel oxides were more variable and less toxic (LC50's of 18 to 130 pg Ni/ml). Most compounds displayed nuclear to cytoplasmic nickel ratios of -1:1.5 to 1:5 (except -1:20 for nickel salts). At the LC50's, a 75-fold range in exposure levels occurred compared to a 1 0-fold range in cytoplasmic and nuclear nickel concentrations, [Nil. Cellular nickel distribution indicated three groupings: inert compounds (green NiO, lithium nickel oxide, relatively low nuclear and cytosolic [Nil); water-soluble salts (very low nuclear [Nil; high cytosolic [Nil), and slightly soluble compounds (relatively high cytosolic and nuclear [Nil). Nickel compounds are considered to be only weak or equivocal mutagens. In this study, a low but significant increase in mutation rate at the gpt locus was shown. Although the results would not be sufficient to deem nickel compounds mutagenic by traditional criteria, characterization by PCR analysis indicated that the spontaneous and nickel-induced mutants exhibited different and compound-specific mutational spectra (thus confirming nickel compound involvement). The results reported illustrate some of the methodologic problems involved in testing "weak" mutagens and indicate that alternative approaches may be necessary in classifying the mutagenicity of nickel and other compounds. -Environ Health Perspect 1 02(Suppl 3): 69-79 (1994).

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Section: Discussionmentioning

confidence: 99%

“…Financial assistance was received from the Nickel Producers Environmental Research Association the ability of nickel to enter the cell by phagocytosis (8)(9)(10). Attempts to explain the mechanism of action and potency differences between various nickel compounds have lead to the "Nickel-Ion Hypothesis" (11,12).…”

Section: Introductionmentioning

confidence: 99%

Toxicity, uptake, and mutagenicity of particulate and soluble nickel compounds.

Fletcher

Rossetto

Turnbull

et al. 1994

Environ Health Perspect

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“…Although it has been established that this electronegative potential plays a role in the process of phagocytosis (1,44), the contribution of charge to virulence in C. neoformans is still uncertain. Comparative zeta potential analysis of intact chronologically young and old cells showed significant differences in electronegative potential.…”

Section: Vol 79 2011 Age-related Dynamics Of C Neoformans Ps Capsumentioning

confidence: 99%

Chronological Aging Is Associated with Biophysical and Chemical Changes in the Capsule of Cryptococcus neoformans

et al. 2011

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Does the age of a microbial cell affect its virulence factors? To our knowledge, this question has not been addressed previously, but the answer is of great relevance for chronic infections where microbial cells persist and age in hosts. Cryptococcus neoformans is an encapsulated human-pathogenic fungus notorious for causing chronic infections where cells of variable age persist in tissue. The major virulence factor for C. neoformans is a polysaccharide (PS) capsule. To understand how chronological age could impact the cryptococcal capsule properties, we compared the elastic properties, permeabilities, zeta potentials, and glycosidic compositions of capsules from young and old cells and found significant differences in all parameters measured. Changes in capsular properties were paralleled by changes in PS molecular mass and density, as well as modified antigenic density and antiphagocytic properties. Remarkably, chronological aging under stationary-phase growth conditions was associated with the expression of ␣-1,3-glucans in the capsule, indicating a new structural capsular component. Our results establish that cryptococcal capsules are highly dynamic structures that change dramatically with chronological aging under prolonged stationary-phase growth conditions. Changes associated with cellular aging in chronic infections could contribute to the remarkable capacity of this fungus to persist in tissues by generating phenotypically and antigenically different capsules.

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“…Since the medium remained the same between samples, the difference in the zeta potential in the irradiated cells suggests dissimilarities in the exposed capsule regions that affect the characteristics of the surface around the cells. Changes in zeta potential may have significance in host interactions, since they have been proposed/shown to affect the outcome of phagocytosis (1,59).…”

Section: Vol 6 2007 Structure Of Radial Regions Of C Neoformans Camentioning

confidence: 99%

Radial Mass Density, Charge, and Epitope Distribution in theCryptococcus neoformansCapsule

Maxson¹,

Dadachova

Casadevall³

et al. 2007

Eukaryot Cell

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Exposure of Cryptococcus neoformans cells to gamma radiation results in a gradual release of capsular polysaccharide, in a dose-dependent manner. This method allows the systematic exploration of different capsular regions. Using this methodology, capsule density was determined to change according to the radial distribution of glucuronoxylomannan and total polysaccharide, becoming denser at the inner regions of the capsule. Scanning electron microscopy of cells following gamma radiation treatment confirmed this finding. The zeta potential of the capsule also increased as the capsule size decreased. However, neither charge nor density differences were correlated with any change in sugar composition (xylose, mannose, and glucuronic acid) in the different capsular regions, since the proportions of these sugars remained constant throughout the capsule. Analysis of the capsular antigenic properties by monoclonal antibody binding and Scatchard analysis revealed fluctuations in the binding affinity within the capsule but not in the number of antibody binding sites, suggesting that the spatial organization of high-and low-affinity epitopes within the capsule changed according to radial position. Finally, evidence is presented that the structure of the capsule changes with capsule age, since the capsule of older cells became more resistant to gamma radiation-induced ablation. In summary, the capsule of C. neoformans is heterogeneous in its spatial distribution and changes with age. Furthermore, our results suggest several mechanisms by which the capsule may protect the fungal cell against exogenous environmental factors.Capsules are a common feature among microorganisms, especially pathogenic bacteria such as Bacillus anthracis, Streptococcus pneumoniae, and Neisseria meningitidis. Microbial capsules can confer particular characteristics, such as protection against stress conditions (64), and are prominent virulence factors. In contrast to the situation in bacteria, extracellular capsules are rare in fungi. The only encapsulated pathogenic fungus is the basidiomycetous yeast Cryptococcus neoformans. This fungus is commonly found in the environment, inhabiting various niches such as pigeon droppings, trees, and water (reviewed in reference 8). The pathogenesis of C. neoformans has been well studied. The yeast is commonly acquired by the host via inhalation. The infection is asymptomatic in immunocompetent hosts. However, in cases of immune suppression, pulmonary infection can be followed by extrapulmonary dissemination of the yeast into other organs, such as spleen, liver, and brain. Untreated cryptococcal meningitis is invariably fatal.The polysaccharide capsule of C. neoformans is considered the main virulence factor of this pathogen (37). Acapsular C. neoformans strains manifest greatly reduced virulence (10, 31), and mutants that produce a larger capsule are hypervirulent (19). The capsule of this yeast is believed to function in protection from desiccation, radiation, and predation by phagocytic organisms (reviewed in...

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The phagocytosis and transforming activity of crystalline metal sulfide particles are related to their negative surface charge

Cited by 57 publications

References 0 publications

Toxicity, uptake, and mutagenicity of particulate and soluble nickel compounds.

Toxicity, uptake, and mutagenicity of particulate and soluble nickel compounds.

Chronological Aging Is Associated with Biophysical and Chemical Changes in the Capsule of Cryptococcus neoformans

Radial Mass Density, Charge, and Epitope Distribution in theCryptococcus neoformansCapsule

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