scholarly journals Role of oxygen-dependent mechanisms in antibody-induced lysis of tumor cells by activated macrophages

1980 ◽  
Vol 152 (1) ◽  
pp. 198-208 ◽  
Author(s):  
C Nathan ◽  
Z Cohn
Keyword(s):  
Hydrogen Peroxide ◽  
Cytochalasin B ◽  
Starch Granules ◽  
Activated Macrophages ◽  
Myristate Acetate ◽  
Lymphoma Cells ◽  
Bacille Calmette Guerin ◽  
Effector Cells ◽  
Hydrogen Peroxide Release

The alloantiserum-dependent lysis of TLX9 lymphoma cells by peritoneal cells from Bacille Calmette-Guerin (BCG)-treated mice was inhibited 62 percent by depletion of oxygen. This effect did not appear to be a result of interference with mitochondrial respiration because cyanide, azide, and dinitrophenol did not inhibit cytotoxicity. Preincubating the effector cells for 2 h without glucose, which markedly reduces their ability to release hydrogen peroxide, likewise suppressed antibody-dependent cytolysis by 62 percent. Lysis of sensitized lymphoma cells was virtually abolished by 6 mg/ml of thioglycollate broth, a concentration that also abrogated the detectable release of hydrogen peroxide and the lysis of lymphoma cells by BCG-activated macrophages in response to phorbol myristate acetate (PMA). This concentration of thioglycollate broth was not toxic to the effector cells, as judged by adherence to plastic, binding of opsonized erythrocytes, and phagocytosis of radiolabeled starch granules. Catalase, superoxide dismutase, horseradish peroxidase, mannitol, ethanol, benzoate, and diazabicyclooctane were without consistent effects. Cytochalasin B and dihydrocytochalasin B both markedly suppressed cytolysis, whether induced by antibody or by PMA (ID(50), 0.5 μg/ml). Cytoehalasin B was an equally potent suppressor of glucose uptake and PMA-induced hydrogen peroxide release by BCG-activated macrophages (ID(50), 0.5 μg/ml). However, dihydrocytochalasin B lacked these latter effects, which suggests that cytotoxicity required intact contractile elements. The extracellular lysis of antibody-coated lymphoma cells by BCG-activated macrophages appears to have a predominantly oxidative basis.

scholarly journals Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity.

1979 ◽  
Vol 149 (1) ◽  
pp. 100-113 ◽  
Author(s):  
C F Nathan ◽  
S C Silverstein ◽  
L H Brukner ◽  
Z A Cohn
Keyword(s):  
Superoxide Dismutase ◽  
Spatial Relation ◽  
Target Cells ◽  
Activated Macrophages ◽  
Lymphoma Cells ◽  
Bacille Calmette Guerin ◽  
Effector Cells ◽  
Marked Inhibition ◽  
Necessary And Sufficient ◽  
Quench Singlet Oxygen

When deprived of oxygen, Bacille Calmette-Guérin (BCG)-activated macrophages no longer lysed P388 lymphoma cells. Both H2O2 release and cytotoxicity by BCG-activated macrophages and by granulocytes triggered with phorbol myristate acetate (PMA) were markedly inhibited when the glucose concentration in the medium was reduced to 0.03 mM or less, or if glucose were replaced with galactose. Catalase abolished PMA-triggered cytotoxicity by both types of effector cells, whereas superoxide dismutase had no effect. Ferricytochrome C reduced the cytotoxicity of BCG-activated macrophages, an effect which was largely reversed by superoxide dismutase. 10 drugs, thought to quench singlet oxygen and/or scavenge hydroxyl radical, did not affect cytotoxicity in this system. Neither azide nor cyanide reduced cytolysis, but there was marked inhibition by lactoperoxidase and iodide. This suggested that cytotoxicity was not dependent upon myeloperoxidase, and that lactoperoxidase may have diverted H2O2 from the oxidation of target cells to oxidation of substances in serum. Mouse erythrocytes, although sensitive targets, interfered with the cytolysis of lymphoma cells, probably by competition for H2O2. Starch particles with covalently bound glucose oxidase resembled macrophages in their spatial relation to the target cells and in the flux of H2O2 they generated from their surface, but were not expected to produce any other potentially toxic products. Such particles lysed lymphoma cells, and the lysis was prevented by catalase. Neither arginase nor thymidine appeared to be involved in cytolysis by BCG-activated macrophages under the conditions used. These findings demonstrated that release of H2O2 was both necessary and sufficient for cytolysis by BCG-activated macrophages and by granulocytes when pharmacologically triggered.

scholarly journals Extracellular cytolysis by activated macrophages and granulocytes. I. Pharmacologic triggering of effector cells and the release of hydrogen peroxide.

1979 ◽  
Vol 149 (1) ◽  
pp. 84-99 ◽  
Author(s):  
C F Nathan ◽  
L H Brukner ◽  
S C Silverstein ◽  
Z A Cohn
Keyword(s):  
Trypan Blue ◽  
Response Curve ◽  
Target Cells ◽  
Activated Macrophages ◽  
Lymphoma Cells ◽  
Effector Cells ◽  
Proteose Peptone ◽  
Standard Assay ◽  
Different Types ◽  
J774 Cells

Lymphoma cells were rapidly lysed by activated macrophages and granulocytes in the presence of PMA. Release of 51Cr from lymphoma cells correlated closely with their destruction as viewed by scanning electron microscopy, and with reduction in the number of trypan blue-excluding cells. The standard assay involved 51 Cr release measured at 4.5 h, but injury appeared to be complete in 1 h. Of eight different types of effector cells tested, only those releasing abundant H2O2 in response to PMA were effective, that, is BCG-, C. parvum-, or casein-activated macrophages, or thioglycollate-elicited granulocytes. Normal macrophages, J774 cells, or macrophages elicited with thioglycollate broth or proteose-peptone were ineffective. BCG-activated macrophages and granulocytes caused 50% specific release of 51Cr from P388 lymphoma cells at E:T ratios between 1.4 and 4.5, and from mouse erythrocytes at E:T ratios of 0.017 to 0.025. 10 types of target cells varied widely in their susceptibility to lysis by reagent H2O2, with one-half maximal lysis occurring at H2O2 concentrations ranging from 3.63 X 10(-6) M to 3.85 X 10(-5) M. Effector cells were expected to generate approximately that much H2O2 during the period of injury. Susceptibility of the target cells to lysis by PMA-triggered granulocytes correlated closely with their sensitivity to H2O2 (r = 0.98). The membrane-active agents LPS and digitonin, which did not trigger H2O2 release, did not trigger cytotoxicity. The dose-response curve for triggering of H2O2 release by PMA was identical to that for triggering cytotoxicity. These results provided strong circumstantial evidence for the importance of H2O2 in extracellular cytolysis by activated macrophages and granulocytes when pharmacologically triggered.

scholarly journals Role of activated macrophages in antibody-dependent lysis of tumor cells.

1980 ◽  
Vol 152 (1) ◽  
pp. 183-197 ◽  
Author(s):  
C Nathan ◽  
L Brukner ◽  
G Kaplan ◽  
J Unkeless ◽  
Z Cohn
Keyword(s):  
Tumor Cells ◽  
Peritoneal Macrophages ◽  
Activated Macrophages ◽  
Fab Fragment ◽  
Bacille Calmette Guerin ◽  
Pharmacologic Agent ◽  
Peritoneal Cells ◽  
Specific Contact ◽  
Cytolytic Response

Treatment of mice with Bacille Calmette-Guérin (BCG) or C parvum activates their peritoneal macrophages to release increased amounts of H2O2, and thereby to lyse extracellular tumor cells, in response to a pharmacologic agent, phorbol myristate acetate (PMA) (1-3). In the present study, the same bacterial vaccines activated peritoneal cells to become cytolytic to lymphoma cells sensitized with alloantiserum, in the absence of PMA. Resident peritoneal cells, or those elicited with thioglycollate broth, were ineffective, not only in PMA-induced lysis, but also in antibody-dependent lysis of tumor cells. The cytolytic effect of BCG peritoneal cells toward sensitized tumor cells appeared to be mediated mostly by macrophages. Cytotoxicity was immunologically specific, contact dependent, rapid, and efficient. Phagocytosis of intact tumor cells was not involved. Alloantiserum-dependent cytolysis was specifically blocked by the Fab fragment of a monoclonal antibody directed against the trypsin-resistant macrophage Fc receptor (FcR II). Thus, tumor cells coated with homologous immunoglobulin interact with FcR II on activated macrophages to trigger an extra-cellular cytolytic response.

scholarly journals Jagged-1 regulates Foxp3 expression and cytokine production in CD4+ T cells

2019 ◽  
Author(s):  
Soichiro Kimura ◽  
Ronald Allen ◽  
Melissa Scola ◽  
Nicholas W Lukacs ◽  
Steven L. Kunkel ◽  
...  
Keyword(s):  
T Cells ◽  
Cytokine Production ◽  
Foxp3 Expression ◽  
Bacille Calmette Guerin ◽  
Altered Expression ◽  
Effector Cells ◽  
T Cell Regulation ◽  
Notch Ligands ◽  
Draining Lymph Nodes

AbstractNotch ligands are present during the interactions between T cells and dendritic cells (DC) and induce a myriad of effects that facilitate the activation of T cells, including the induction of T cell regulation, survival, and cytokine production. Although the ligands Delta-like 4 and Delta-like 1 are expressed as a function of DC activation, the notch ligand Jagged-1 is constitutively expressed on DC. We sought to determine the role of Jagged-1 in the interactions between CD4+ T cells and DC. We observed that Jagged-1 regulates Foxp3 expression, and Cd11cCre+Jaggedff mice have an altered expression of Foxp3 in effector cells that arise as a result of infection with the mycobacterium Bacille Calmette-Guerin. The observed changes in Foxp3 expression were correlated with an increase in cytokine production from cultures of antigen-stimulated draining lymph nodes.

Experimental oxygen concentration influences rates of mitochondrial hydrogen peroxide release from cardiac and skeletal muscle preparations

2020 ◽  
Vol 318 (5) ◽  
pp. R972-R980
Author(s):  
Lance C. Li Puma ◽  
Michael Hedges ◽  
Joseph M. Heckman ◽  
Alissa B. Mathias ◽  
Madison R. Engstrom ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Hydrogen Peroxide ◽  
Amplex Red ◽  
Chemical Background ◽  
Tissue Homogenates ◽  
Final Electron ◽  
Hydrogen Peroxide Release ◽  
Permeabilized Fibers ◽  
Final Electron Acceptor

Mitochondria utilize the majority of oxygen (O2) consumed by aerobic organisms as the final electron acceptor for oxidative phosphorylation (OXPHOS) but also to generate reactive oxygen species (mtROS) that participate in cell signaling, physiological hormesis, and disease pathogenesis. Simultaneous monitoring of mtROS production and oxygen consumption ( Jo2) from tissue mitochondrial preparations is an attractive investigative approach, but it introduces dynamic changes in media O2 concentration ([O2]) that can confound experimental results and interpretation. We utilized high-resolution fluorespirometry to evaluate Jo2 and hydrogen peroxide release ( Jh2o2) from isolated mitochondria (Mt), permeabilized fibers (Pf), and tissue homogenates (Hm) prepared from murine heart and skeletal muscle across a range of experimental [O2]s typically encountered during respirometry protocols (400–50 µM). Results demonstrate notable variations in Jh2o2 across tissues and sample preparations during nonphosphorylating (LEAK) and OXPHOS-linked respiration states at 250 µM [O2] but a linear decline in Jh2o2 of 5–15% per 50-µM decrease in chamber [O2] in all samples. Jo2 was generally stable in Mt and Hm across [O2]s above 50 µM but tended to decline below 250 µM in Pf, leading to wide variations in assayed rates of Jh2o2/O2 across chamber [O2]s and sample preparations. Development of chemical background fluorescence from the H2O2 probe (Amplex Red) was also O2 sensitive, emphasizing relevant calibration considerations. This study highlights the importance of monitoring and reporting the chamber [O2] at which Jo2 and Jh2o2 are recorded during fluorespirometry experiments and provides a basis for selecting sample preparations for studies addressing the role of mtROS in physiology and disease.

scholarly journals Role of arginase in killing of schistosomula of schistosoma mansoni

1980 ◽  
Vol 151 (6) ◽  
pp. 1557-1562 ◽  
Author(s):  
GR Olds ◽  
JJ Ellner ◽  
LA Kearse ◽  
JW Kazura ◽  
AAF Mahmoud
Keyword(s):  
Schistosoma Mansoni ◽  
Acquired Resistance ◽  
Multicellular Organism ◽  
Infectious Agents ◽  
Activated Macrophages ◽  
Myristate Acetate ◽  
Nonspecific Resistance ◽  
Cell Monolayers

Nonspecific resistance to the multicellular organism Schistosoma mansoni can be induced in mice by several infectious agents. We utilized the observed genetic restriction of such acquired resistance to study the mediators of killing of the larval stage of S. mansoni in vitro. Adherent peritoneal cell monolayers from Corynebacterium parvum-treated C57BL/6J but not from C. parvum-treated BALB/cJ mice killed an increased proportion of schistosomula in 24 h. Activated macrophages (Mφ) from both strains exhibited enhanced H(2)0(2) production after incubation with the parasites or phorbol myristate acetate. Thus H(2)0(2) production was not associated with schistosomula killing. Moreover, schistosomula killing was unaffected by catalase or superoxide dismutase. In contrast, activated C57BL/6J (but not BALB/cJ) Mφ released fourfold more arginase into supernates than control Mφ. Schistosomula killing by these Mφ correlated with arginase content of the supernates, was exaggerated in arginine-poor medium, and could be blocked by the addition of arginine. Exogenous bovine arginase added to Fischer's medium without macrophages produced comparable parasite mortality. Our data suggest that arginase is a critical mediator of in vitro killing of this multicellular organism by activated macrophages.

scholarly journals Angiotensin Type 1a Receptor Signaling Is Not Necessary for the Production of Reactive Oxygen Species in Polymorphonuclear Leukocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Fumiko Yamato ◽  
Junji Takaya ◽  
Shoji Tsuji ◽  
Masafumi Hasui ◽  
Kazunari Kaneko
Keyword(s):  
Hydrogen Peroxide ◽  
Polymorphonuclear Leukocytes ◽  
No Production ◽  
Polymorphonuclear Leucocytes ◽  
Oxygen Species ◽  
Ang Ii ◽  
Wild Type ◽  
Myristate Acetate ◽  
At1a Receptor

Background. Although angiotensin II (Ang II) has inflammatory effects, little is known about its role in polymorphonuclear leucocytes (PMLs). To elucidate the role of Ang II in PMLs ROS production, we examined hydrogen peroxide (H2O2), one of the ROS, and NO production in AT1a receptor knockout (AT1KO) mice. Methods and Results. PMLs were analyzed from Ang II type 1a receptor knockout mice (AT1KO) and C57BL/6 wild type mice. Using flow cytometry, we studied hydrogen peroxide (H2O2) production from PMLs after Staphylococcus aureus phagocytosis or phorbol myristate acetate (PMA) stimulation. Nitric oxide (NO) production in the AT1KO was low at basal and after phagocytosis. In the AT1KO, basal H2O2 production was low. After PMA or phagocytosis stimulation, however, H2O2 production was comparable to wild type mice. Next we studied the H2O2 production in C57BL/6 mice exposed to Ang II or saline. H2O2 production stimulated by PMA or phagocytosis did not differ between the two groups. Conclusions. AT1a pathway is not necessary for PMLs H2O2 production but for NO production. There was a compensatory pathway for H2O2 production other than the AT1a receptor.

The role of copper ions in hydrogen peroxide bleaching: Their origin, removal, and effect on pulp quality

TAPPI Journal ◽  
2012 ◽  
Vol 11 (7) ◽  
pp. 37-46 ◽  
Author(s):  
PEDRO E.G. LOUREIRO ◽  
SANDRINE DUARTE ◽  
DMITRY V. EVTUGUIN ◽  
M. GRAÇA V.S. CARVALHO
Keyword(s):  
Hydrogen Peroxide ◽  
Copper Ions ◽  
Peroxide Bleaching ◽  
Metals Removal ◽  
Peroxide Decomposition ◽  
Equipment Corrosion ◽  
And Performance ◽  
And Control ◽  
Main Effects

This study puts particular emphasis on the role of copper ions in the performance of hydrogen peroxide bleaching (P-stage). Owing to their variable levels across the bleaching line due to washing filtrates, bleaching reagents, and equipment corrosion, these ions can play a major role in hydrogen peroxide decomposition and be detrimental to polysaccharide integrity. In this study, a Cu-contaminated D0(EOP)D1 prebleached pulp was subjected to an acidic washing (A-stage) or chelation (Q-stage) before the alkaline P-stage. The objective was to understand the isolated and combined role of copper ions in peroxide bleaching performance. By applying an experimental design, it was possible to identify the main effects of the pretreatment variables on the extent of metals removal and performance of the P-stage. The acid treatment was unsuccessful in terms of complete copper removal, magnesium preservation, and control of hydrogen peroxide consumption in the following P-stage. Increasing reaction temperature and time of the acidic A-stage improved the brightness stability of the D0(EOP)D1AP bleached pulp. The optimum conditions for chelation pretreatment to maximize the brightness gains obtained in the subsequent P-stage with the lowest peroxide consumption were 0.4% diethylenetriaminepentaacetic acid (DTPA), 80ºC, and 4.5 pH.

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