scholarly journals Murine Kupffer cells. Mononuclear phagocytes deficient in the generation of reactive oxygen intermediates.

1985 ◽  
Vol 161 (5) ◽  
pp. 1079-1096 ◽  
Author(s):  
D A Lepay ◽  
C F Nathan ◽  
R M Steinman ◽  
H W Murray ◽  
Z A Cohn
Keyword(s):  
Kupffer Cells ◽  
Leishmania Donovani ◽  
Reactive Oxygen ◽  
Antigen Expression ◽  
Peritoneal Macrophages ◽  
Mononuclear Phagocytes ◽  
High Yield ◽  
Reactive Oxygen Intermediates ◽  
Oxygen Intermediates

Murine Kupffer cells (KC) were isolated by a high yield collagenase perfusion technique. The morphology, surface markers, and secretory products were typical of macrophages in other tissues. However, KC released negligible levels of H2O2 and O-2, in contrast to peritoneal macrophages. KC oxygen consumption was not increased by agents triggering a respiratory burst in peritoneal cells. Moreover, KC capacity to secrete reactive oxygen intermediates (ROI), in contrast to Ia antigen expression, was not enhanced by exposure to lymphokines or recombinant gamma interferon. The selective defect in KC oxidative response was paralleled by impaired in vitro killing of Toxoplasma gondii trophozoites and Leishmania donovani promastigotes and amastigotes. Deficient secretion of ROI by KC might protect hepatocytes and erythrocytes from injury during endocytosis by KC, but might render the liver more susceptible to parasitization by organisms that are primarily killed through oxygen-dependent mechanisms.

scholarly journals Coxiella burnetiiAcid Phosphatase Inhibits the Release of Reactive Oxygen Intermediates in Polymorphonuclear Leukocytes

2010 ◽  
Vol 79 (1) ◽  
pp. 414-420 ◽  
Author(s):  
J. Hill ◽  
J. E. Samuel
Keyword(s):  
Acid Phosphatase ◽  
Nadph Oxidase ◽  
Polymorphonuclear Leukocytes ◽  
Q Fever ◽  
Reactive Oxygen ◽  
Host Cells ◽  
Reactive Oxygen Intermediates ◽  
Oxygen Intermediates

ABSTRACTCoxiella burnetii, the etiological agent of Q fever, is a small, Gram-negative, obligate intracellular bacterium. Replication ofC. burnetiiduring infection has been shown to be increased by decreasing oxidative stress using p47phox −/−and iNOS−/−micein vivoand by pharmacologic inhibitorsin vitro. Building upon this model, we investigated the role polymorphonuclear leukocytes (PMN) play in the control of infection, since NADPH oxidase-mediated release of reactive oxygen intermediates (ROI) is a primary bactericidal mechanism for these cells that is critical for early innate clearance. Earlier studies suggested thatC. burnetiiactively inhibited release of ROI from PMN through expression of an unidentified acid phosphatase (ACP). Recent genomic annotations identified one open reading frame (CBU0335) which may encode a Sec- and type II-dependent secreted ACP. To test this model, viableC. burnetiipropagated in tissue culture host cells or axenic media,C. burnetiiextracts, or purified recombinant ACP (rACP) was combined with human PMN induced with 4-phorbol 12-myristate 13-acetate (PMA). The release of ROI was inhibited when PMN were challenged with viableC. burnetii,C. burnetiiextracts, or rACP but not when PMN were challenged with electron beam-inactivatedC. burnetii. C. burnetiiextracts and rACP were also able to inhibit PMA-induced formation of NADPH oxidase complex on PMN membranes, suggesting a molecular mechanism responsible for this inhibition. These data support a model in whichC. burnetiieludes the primary ROI killing mechanism of activated PMN by secreting at least one acid phosphatase.

H2O2-Induced Apoptosis of Thymocytes Involves Mobilization of Divalent Cations

2002 ◽  
Vol 15 (3) ◽  
pp. 195-200 ◽  
Author(s):  
A. Acharya
Keyword(s):  
Divalent Cations ◽  
Reactive Oxygen ◽  
Time Dependent ◽  
Dependent Manner ◽  
Reactive Oxygen Intermediates ◽  
Oxygen Intermediates ◽  
Thymocyte Apoptosis ◽  
Induced Apoptosis

More than 90% of thymocytes undergo apoptosis while undergoing differentiation in the thymus. Although several factors act in concert to induce thymocyte apoptosis, it remains speculative if reactive oxygen intermediates produced by thymic macrophages may play a role in this process. The present investigation was carried out to determine if H2O2 is capable of inducing apoptosis of thymocytes in vitro. It was observed that H2O2 could induce apoptosis of thymocytes in vitro in a dose and time dependent manner. It was further found that H2O2-induced thymocyte apoptosis was dependent on the mobilization of divalent cations. The result of this study will help further in the understanding of the mechanism of H2O2 - induced apoptosis.

Reactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro

1992 ◽  
Vol 73 (5) ◽  
pp. 1797-1804 ◽  
Author(s):  
M. B. Reid ◽  
K. E. Haack ◽  
K. M. Franchek ◽  
P. A. Valberg ◽  
L. Kobzik ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
High Frequency ◽  
Low Frequency ◽  
Reactive Oxygen ◽  
Muscular Contraction ◽  
Fiber Bundles ◽  
Reactive Oxygen Intermediates ◽  
Oxygen Intermediates ◽  
Low Frequency Fatigue

We hypothesized that muscle fiber bundles produce reactive oxygen intermediates and that reactive oxidant species contribute to muscular fatigue in vitro. Fiber bundles from rat diaphragm were mounted in chambers containing Krebs-Ringer solution. In studies of intracellular oxidant kinetics, bundles were loaded with 2′,7′-dichlorofluorescin, a fluorochrome that emits at 520 nm when oxidized; emissions were quantified using a fluorescence microscope. Emissions from unstimulated muscles increased over time (P < 0.001). Accumulation of fluorescence was slowed by addition of catalase (P < 0.001) or superoxide dismutase (P < 0.001) and was accelerated by repetitive muscular contraction (P < 0.05). To determine effects of reactive oxygen intermediates on fatigue, curarized bundles were stimulated to contract isometrically; force was measured. Catalase, superoxide dismutase, and dimethyl sulfoxide were screened for effects on low- and high-frequency fatigue. Antioxidants inhibited low-frequency fatigue [after 5 min of repetitive contractions, force at 30 Hz was 20% greater than control (P < 0.015)] and increased the variability of fatigue at 30 Hz (P < 0.03). Antioxidants did not alter high-frequency (200-Hz) fatigue. We conclude that 1) diaphragm fiber bundles produce reactive oxygen intermediates, including O2-. and H2O2; 2) muscular contraction increases intracellular oxidant levels; and 3) reactive oxygen intermediates promote low-frequency fatigue in this preparation.

scholarly journals Modulation of Intracellular Formation of Reactive Oxygen Intermediates in Peritoneal Macrophages and Microglia/Brain Macrophages by Propentofylline

1994 ◽  
Vol 14 (1) ◽  
pp. 145-149 ◽  
Author(s):  
R. B. Banati ◽  
P. Schubert ◽  
G. Rothe ◽  
J. Gehrmann ◽  
K. Rudolphi ◽  
...  
Keyword(s):  
Cell Death ◽  
Reactive Oxygen ◽  
Peritoneal Macrophages ◽  
Microglial Cells ◽  
Reactive Oxygen Intermediates ◽  
Respiratory Burst Activity ◽  
Brain Macrophages ◽  
Oxygen Intermediates ◽  
Pathological Conditions ◽  
Nerve Cell Death

Ischemia-induced nerve cell death can partly be prevented by propentofylline, a pharmacon structurally related to xanthine derivates that interacts with the neuromodulatory function of endogenous adenosine. To evaluate a possible mechanism of neuroprotection by propentofylline, we studied its effect on the cellular production of reactive oxygen intermediates in microglial cells, which under pathological conditions can differentiate into brain macrophages, in comparison to peritoneal macrophages. Using a flow cytometric assay, we determined the intracellular formation of reactive oxygen intermediates by measuring the oxidation of the membrane-permeable and nonfluorescent dihydrorhodamine 123 to the cationic and intracellularly trapped, green fluorescent rhodamine 123 in single viable cells. Propentofylline at the therapeutic concentration of 50 μ M completely inhibited the Ca2+-dependent Con A-induced increase in the production of reactive oxygen intermediates in peritoneal macrophages. In isolated and cultured microglial cells, which have a high spontaneous respiratory burst activity, the spontaneous production of reactive oxygen intermediates was reduced by ∼30%. A phorbol 12-myristate 13-acetate-induced rise in the respiratory burst activity could not be inhibited by propentofylline in either cell type. An increased generation of reactive oxygen intermediates is thought to contribute to nerve cell death after brain ischemia, edema, and neurodegenerative diseases like Alzheimer's disease. These pathological conditions are all accompanied by an activation of microglial cells. We therefore suggest that the neuroprotective properties of propentofylline might in part be due to a modulation of the microglial production of potentially harmful reactive oxygen intermediates.

scholarly journals Involvement of Reactive Oxygen Intermediates in Spontaneous and CD95(Fas/APO-1)–Mediated Apoptosis of Neutrophils

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1748-1753 ◽  
Author(s):  
Yoshihito Kasahara ◽  
Kazuyuki Iwai ◽  
Akihiro Yachie ◽  
Kunio Ohta ◽  
Akihiro Konno ◽  
...  
Keyword(s):  
Signal Transduction Pathway ◽  
Reactive Oxygen ◽  
Reactive Oxygen Intermediates ◽  
Transduction Pathway ◽  
Spontaneous Apoptosis ◽  
Oxygen Intermediates ◽  
Hereditary Defect ◽  
Oxidative Products

Apoptosis is well known to be mediated by oxidative stress. To evaluate the functional role of reactive oxygen intermediates (ROI) produced by neutrophils, we compared the rates of apoptosis in neutrophils isolated from normal donors and from patients with chronic granulomatous disease (CGD), a hereditary defect in ROI production. Spontaneous cell death in CGD neutrophils in vitro was significantly inhibited relative to normal neutrophils. The acceleration of apoptosis induced by anti-Fas monoclonal antibody (MoAb) in CGD neutrophils was much slower than that seen in normal neutrophils. These findings suggest that the apoptosis of neutrophils may be mediated by endogenous oxidative products. This suggestion was confirmed by observation that apoptosis of normal neutrophils was markedly inhibited by reduction of intracellular levels of hydrogen peroxide (H2O2 ). The inhibition of apoptosis in normal neutrophils by adding catalase occurred regardless of the presence of anti-Fas MoAb. H2O2 increased both spontaneous apoptosis and Fas-mediated apoptosis of the CGD neutrophils in proportion to that seen in normal neutrophils. Although several factors that mediate the apoptosis of neutrophils remain to be determined, these results suggest that ROI are major mediators of the apoptosis in neutrophils and may be involved in Fas-mediated signal transduction pathway.

scholarly journals The origin, kinetics, and characteristics of the kupffer cells in the normal steady state

1978 ◽  
Vol 148 (1) ◽  
pp. 1-17 ◽  
Author(s):  
RW Crofton ◽  
MMC Diesselhoff-Den Dulk ◽  
RV Furth
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Kupffer Cells ◽  
Peritoneal Macrophages ◽  
Turnover Time ◽  
Mononuclear Phagocytes ◽  
Labeling Index ◽  
Cell Labeling ◽  
Initial Suspension

Enzymatic digestion with pronase and DNAase was used to isolate Kupffer cells from mouse liver. The characteristics of these cells were found to be similar to those of peritoneal macrophages, except that in the initial suspension the percentage of Kupffer cells with Fc receptors was low, C receptors were absent and the ingestion of opsenized bacteria was very poor, because of the effect of pronase on the cell membrane. After 24 h incubation in vitro all these characteristics return. The in vitro and 1 h-pulse [(3)H]thymidine labeling of the Kupffer cells is low (0.8 and 1 percent, respectively) indicating that in essence these cells do not divide. It was also shown that the small percentage of in vitro labeled Kupffer cells was recently derived from the circulation. After an intravenous injection of zymosan the in vitro labeling index of the Kupffer cells increased 16-fold, but it was proven that these dividing cells were immature mononuclear phagocytes very recently recruited from the bone marrow. The labeling of Kupffer cells aider one or four injections of [(3)H]thymidine reached a peak of 10.4 percent at 48 h or 24.1 percent at 60 h, respectively, indicating that these cells are derived from labeled monocytes. Further evidence for this conclusion was obtained by the absence of an increase of labeled Kupffer cells during treatment with hydrocortisone, which causes a monocytopenia during which no circulating monocytes are available to migrate to the tissues. Labeling studies in animals X-irradiated with hind-limb shielding gave a Kupffer cell labeling index of 5-10 percent of the normal values, which confirms their bone marrow origin. A quantitative study on the production of labeled monocytes in the bone marrow and their transit through the circulation showed that in the normal steady state at least 56.4 percent of the monocytes leaving the circulation become Kupffer cells. Considering the Kupffer cells as kinetically homogeneous this gives a mean turnover time of the total population of Kupffer cells of 21 days.

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