Role for Endogenous and Acquired Peroxidase in the Toxoplasmacidal Activity of Murine and Human Mononuclear Phagocytes

Locksley, Richard M.; Wilson, Christopher; Klebanoff, Seymour J.

doi:10.1172/jci110545

Cited by 88 publications

(58 citation statements)

References 40 publications

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“…The organisms were harvested by peritoneal lavage, separated from leukocytes by filtration through a 3-,um polycarbonate filter (Nuclepore), washed three times, and suspended at 107 T. gondii per ml in Krebs-Ringer phosphate buffer (pH 7.4) containing 5.5 mM glucose (KRPG buffer) as described (9). Organisms prepared in this fashion were >90% viable as assessed by acridine orange-ethidium bromide fluorescence (9). In selected studies, T. gondii were heat-killed by incubation at 100°C (Sigma).…”

Section: Methodsmentioning

confidence: 99%

“…After allowing the mixture to settle and then shaking them for 60 min at 37°C, supernatants were harvested into iced tubes and cleared by centrifugation. Superoxide dismutase-inhibitable ferricytochrome c reduction was used to calculate superoxide anion (O2 ) generation (9), and the oxidation of scopoletin was used to calculate H202 production as described (10).…”

Section: Methodsmentioning

confidence: 99%

“…Macrophage monolayers were established on 15-mm glass coverslips as described (9) and challenged with zymosan or T. gondii at the same concentrations used for the generation of LT. At the indicated time points, coverslips were washed to remove nonadherent particles, fixed in 2.5% glutaraldehyde, and stained with Dif-Quik. The number of ingested particles per cell was assessed microscopically under oil immersion.…”

Section: Methodsmentioning

confidence: 99%

“…Murine Peritoneal Macrophages. Resident peritoneal cells were collected in Ca2+/Mg2+-free Hanks' balanced salt solution (GIBCO) by lavage of 5-to 8-week-old BALB/c or C57BL/6 mice as described (9). Corynebacterium parvumactivated peritoneal macrophages were collected similarly from animals that had been given 1.4 mg of C. parvum suspension (Wellcome) intraperitoneally 12 days previously.…”

Section: Each Of These Compounds Incorporated [3h]arachidonic Acidmentioning

confidence: 99%

“…Corynebacterium parvumactivated peritoneal macrophages were collected similarly from animals that had been given 1.4 mg of C. parvum suspension (Wellcome) intraperitoneally 12 days previously. Macrophage monolayers were established by adherence followed by washing in 35-mm tissue culture dishes as described (9). The addition of 6 x 106 macrophages per dish yielded z300 ,ug ofadherent protein when using resident cells and -400 ug of adherent protein when using C. parvumactivated cells.…”

Section: Each Of These Compounds Incorporated [3h]arachidonic Acidmentioning

confidence: 99%

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Alteration of leukotriene release by macrophages ingesting Toxoplasma gondii.

Locksley¹,

Fankhauser²,

Henderson³

1985

Proc. Natl. Acad. Sci. U.S.A.

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Mouse resident peritoneal macrophages incubated with ionophore A23187 or opsonized zymosan released leukotrienes (LT) B4 and C4 (LTB4 and LTC4) and LTC4 and LTD4, respectively. In contrast, incubation with Toxoplasma gondii, an obligate intracellular protozoan, led to the formation of 11-, 12-, and 15-hydroxyicosatetraenoic acids (HETEs), together with an unidentified compound, designated compound X. Each of these compounds incorporated [3H]arachidonic acid from the macrophage during phagocytosis of T. gondi. Compound X migrated immediately prior to 15-HETE by reversephase HPLC and was distinct from authentic monoHETE, monohydroperoxyicosatetraenoic acid (mono-HPETE), and dihydroxyicosatetraenoic acid (diHETE) standards. The generation of compound X by macrophages correlated with the extent of phagocytosis of T. gondii and with intracellular survival of the organisms. Prior antibody-coating of T. gondii or activation of macrophages, either of which inhibited survival and replication of ingested organisms, was associated with production of LTD4 but not compound X. Killed organisms also stimulated LTD4 release only. Although T. gondii concentrated arachidonic acid, they did not metabolize the compound to identifiable lipoxygenase products. Preincubation of macrophages with the relative lipoxygenase inhibitors nordihydroguaiaretic acid or 5,8,11,14-icosatetraynoic acid inhibited the formation of compound X. The absence of leukotriene production by macrophages ingesting T. gondji may explain the relative lack of a neutrophil inflammatory response in diseases due to obligate intracellular organisms. Alternatively, compound X may have functional activities that might mediate some of the host responses to cellular parasitism.The leukotrienes (LT) have been identified as potentially important inflammatory mediators of host defense (1, 2). LTB4 is a potent neutrophil chemoattractant and stimulus for aggregation, degranulation, and adherence to endothelium. The sulfidopeptide leukotrienes LTC4, LTD4, and LTE4, which collectively constitute the slow-reacting substance of anaphylaxis (SRS), promote vasoconstriction and enhance permeability across the postcapillary venule. Resident tissue macrophages are major sources of the LT (3-5). The plasma membrane of these cells is rich in esterified arachidonate that is released during membrane perturbation and is then available to Ca2+-dependent 5-lipoxygenase that regulates the formation of the LT (6, 7). Traditional stimuli for LT production by macrophages in vitro include both soluble (calcium ionophore A23187, endotoxin, phorbol myristate acetate) and particulate (zymosan, immunocomplexes) stimuli; LT production in response to the latter has been related directly to the degree of phagocytosis (3-5).Resident tissue macrophages are the initial target of many obligate intracellular pathogens that infect man, but the capacity of viable organisms to trigger the release of inflammatory mediators from macrophages has not been systematically investigated. The pathogenic protozoa...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Each Of These Compounds Incorporated [3h]arachidonic Acidmentioning

confidence: 99%

Section: Each Of These Compounds Incorporated [3h]arachidonic Acidmentioning

confidence: 99%

See 3 more Smart Citations

Alteration of leukotriene release by macrophages ingesting Toxoplasma gondii.

Locksley¹,

Fankhauser²,

Henderson³

1985

Proc. Natl. Acad. Sci. U.S.A.

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Oxidative Response of Phagocytes to Parasite Invasion

Klebanoff

Locksley

Jong

et al. 1983

Ciba Foundation Symposium 99 ‐ Cytopathology of Parasitic Disease

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Biodegradable Elastomers and Gels for Elastic Electronics

Chen

Chu

et al. 2022

Advanced Science

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Biodegradable electronics are considered as an important bio‐friendly solution for electronic waste (e‐waste) management, sustainable development, and emerging implantable devices. Elastic electronics with higher imitative mechanical characteristics of human tissues, have become crucial for human‐related applications. The convergence of biodegradability and elasticity has emerged a new paradigm of next‐generation electronics especially for wearable and implantable electronics. The corresponding biodegradable elastic materials are recognized as a key to drive this field toward the practical applications. The review first clarifies the relevant concepts including biodegradable and elastic electronics along with their general design principles. Subsequently, the crucial mechanisms of the degradation in polymeric materials are discussed in depth. The diverse types of biodegradable elastomers and gels for electronics are then summarized. Their molecular design, modification, processing, and device fabrication especially the structure–properties relationship as well as recent advanced are reviewed in detail. Finally, the current challenges and the future directions are proposed. The critical insights of biodegradability and elastic characteristics in the elastomers and gel allows them to be tailored and designed more effectively for electronic applications.

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Role for Endogenous and Acquired Peroxidase in the Toxoplasmacidal Activity of Murine and Human Mononuclear Phagocytes

Cited by 88 publications

References 40 publications

Alteration of leukotriene release by macrophages ingesting Toxoplasma gondii.

Alteration of leukotriene release by macrophages ingesting Toxoplasma gondii.

Oxidative Response of Phagocytes to Parasite Invasion

Biodegradable Elastomers and Gels for Elastic Electronics

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