The role of oxidants and vitamin C on neutrophil apoptosis and clearance

2004 ◽  
Vol 32 (3) ◽  
pp. 499-501 ◽  
Author(s):  
M.C.M. Vissers ◽  
M.B. Hampton
Keyword(s):  
Vitamin C ◽  
Chronic Granulomatous Disease ◽  
Surface Expression ◽  
Neutrophil Apoptosis ◽  
Granulomatous Disease ◽  
Probable Outcome ◽  
Induced Apoptosis ◽  
Deficient Mice ◽  
Surface Changes

We have investigated the role of neutrophil oxidants in the surface changes that result in recognition and uptake of neutrophils by macrophages. We have shown that H2O2 produced by stimulated neutrophils is essential for the surface expression of phosphatidylserine. This does not occur in neutrophils from mice with chronic granulomatous disease and may explain the formation of granuloma in this condition. We have also investigated the role of intracellular vitamin C on neutrophil apoptosis. Cells from vitamin C-deficient mice were found to be less likely to undergo both spontaneous and oxidant-induced apoptosis, with eventual necrosis being the most probable outcome.

scholarly journals Estrogen binding by leukocytes during phagocytosis,.

1977 ◽  
Vol 145 (4) ◽  
pp. 983-998 ◽  
Author(s):  
S J Klebanoff
Keyword(s):  
Chronic Granulomatous Disease ◽  
Reaction Mechanisms ◽  
Dehydrogenase Deficiency ◽  
Cell Types ◽  
Neutrophil Function ◽  
Granulomatous Disease ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Estrogen Binding ◽  
Two Populations

Estradiol binds covalently to normal leukocytes during phagocytosis. The binding involves three cell types, neutrophils, eosinophils, and monocytes and at least two reaction mechanisms, one involving the peroxidase of neutrophils and monocytes (myeloperoxidase [MPO]) and possibly the eosinophil peroxidase, and the second involving catalase. Binding is markedly reduced when leukocytes from patients with chronic granulomatous disease (CGD), severe leukocytic glucose 6-phosphate dehydrogenase deficiency, and familial lipochrome histiocytosis are employed and two populations of neutrophils, one which binds estradiol and one which does not, can be demonstrated in the blood of a CGD carrier. Leukocytes from patients with hereditary MPO deficiency also bind estradiol poorly although the defect is not as severe as in CGD. These findings are discussed in relation to the inactivation of estrogens during infection and the possible role of estrogens in neutrophil function.

Role of oxygen intermediates in cytotoxicity: Studies in chronic granulomatous disease

Inflammation ◽  
1993 ◽  
Vol 17 (1) ◽  
pp. 77-92 ◽  
Author(s):  
Robert L. Roberts ◽  
Bonnie J. Ank ◽  
Michael W. Fanger ◽  
Li Shen ◽  
E. Richard Stiehm
Keyword(s):  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Oxygen Intermediates ◽  
Cytotoxicity Studies

Further evaluation of luminol-enhanced luminescence in the diagnosis of disorders of leukocyte oxidative metabolism: role of myeloperoxidase.

1983 ◽  
Vol 29 (3) ◽  
pp. 513-515 ◽  
Author(s):  
M S Cohen ◽  
P S Shirley ◽  
L R DeChatelet
Keyword(s):  
Chronic Granulomatous Disease ◽  
Oxidative Metabolism ◽  
Clinical Consequence ◽  
Granulomatous Disease ◽  
Myeloperoxidase Deficiency ◽  
Luminescence Assay ◽  
Diagnostic Confusion ◽  
Enhanced Luminescence ◽  
Hereditary Nature

Abstract Chemiluminescence can be used to identify defects in the oxidative metabolism of granulocytes. This procedure has recently been adopted for use with microliter quantities of whole blood, appropriate for prenatal or neonatal study. Although the contribution of myeloperoxidase to the chemiluminescence assay has been noted, the possible diagnostic confusion between chronic granulomatous disease of childhood (which is rare and severe) and myeloperoxidase deficiency (which is common and of little clinical consequence) has not been stressed. We report a father and his infant daughter whose cells emitted no light in the luminol-enhanced luminescence assay; both patients are totally peroxidase deficient. These results emphasize the hereditary nature of myeloperoxidase deficiency, and the possibility for erroneous diagnosis of chronic granulomatous disease of childhood based on the luminol-enhanced luminescence test.

Deletion of OLFM4 Rescues Defective Host Defense Against Staphylococcus Aureus, but Not Aspergillus Fumigatus in Murine X-Linked Chronic Granulomatous Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3276-3276
Author(s):  
Wenli Liu ◽  
Janyce A Sugui ◽  
Hongzhen Li ◽  
Kyung J Kwon-Chung ◽  
Griffin P. Rodgers
Keyword(s):  
Staphylococcus Aureus ◽  
Innate Immunity ◽  
Chronic Granulomatous Disease ◽  
Host Defense ◽  
Cathepsin G ◽  
Granulomatous Disease ◽  
Wild Type ◽  
Cathepsin C ◽  
Host Innate Immunity ◽  
Deficient Mice

Abstract Abstract 3276 Introduction: Chronic granulomatous disease (CGD) patients have recurrent life-threating bacterial and fungal infections due to the mutation of one of four subunits of the respiratory burst oxidase (NADPH-oxidase). Currently, the overall fatality rate in CGD patients remains high, making it necessary to better understand the basic biological processes governing host defense against bacteria and fungi in CGD. Olfactomedin 4 (OLFM4) is a neutrophil granule protein, which has been recently identified as a negative regulator of host innate immunity against bacteria infection in mice through modulation of neutrophil protease activity. The goal of this study was to evaluate the impact of OLFM4 deletion on host innate immunity against Staphylococcus aureus and Aspergillus fumigatus, two major pathogens encountered in CGD patients, in a murine X-linked CGD model. Results: We created gp91phox-and OLFM4-double deficient mice and investigated the mice defense against S. aureus and A. fumigatus infection. We found that neutrophil intracellular killing and in vivo clearance of S. aureus have been significantly increased in gp91phox- and OLFM4-double deficiency mice compared with CGD mice. The mice survival to S. aureus sepsis in gp91phox- and OLFM4-double deficiency mice has also been significantly prolonged compared with CGD mice. Our study has shown that the CGD mice immune deficiency against S. aureus has been totally corrected by additional loss of OLFM4 gene. To explore the mechanism that OLFM4 deletion rescued the bactericidal activities of CGD neutrophils, we analyzed cathepsin C and its downstream protease (neutrophil elastase and cathepsin G) activities in the mice neutrophils. Cathepsin C activities in OLFM4 deficient as well as double deficient mice neutrophils were significantly higher than those in WT mouse neutrophils. Cathepsin C activities in the neutrophils of CGD were similar to those in WT mice. Accordingly, the elastase and cathepsin G activities in the neutrophils of OLFM4 deficient and double deficient mice were also substantially higher than those in WT mice as well as CGD mice. However, we have not observed enhanced innate immunity against A. fumigatus in OLFM4 deficiency mice compared with wild-type mice using a lung infection model. The lung histopathology showed similar inflammation and fungal burden in the OLFM4 deficiency mice compared with wild-type mice. Correspondingly, mice survival to severe A. fumigatus infection did not show significant difference in gp91phox- and OLFM4-double deficiency mice compared with CGD mice, suggesting that OLFM4 may not play a role in mice host defense against A. fumigatus. Conclusion: 1. The damaged neutrophil bacterial killing and host innate immunity against S. aureus in CGD mice due to oxidative mechanism deficiency could be successfully rescued by deletion of OLFM4. 2. These results showed that the granule protease activities in CGD neutrophils could be substantially enhanced above the level in normal neutrophils by deletion of OLFM4, suggesting that the increased of serine proteinase activities due to OLFM4 deletion is NADPH-independent. 3. OLFM4 may not play a role in mice host defense against pulmonary A. fumigatus infection. 4. OLFM4 might prove to be an important target in CGD patients to augment host defense against bacterial infection. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Karolina Bień ◽  
Justyna Sokołowska ◽  
Piotr Bąska ◽  
Zuzanna Nowak ◽  
Wanda Stankiewicz ◽  
...  
Keyword(s):  
T Cells ◽  
Inflammatory Response ◽  
Fas Ligand ◽  
Antiviral Response ◽  
Target Cells ◽  
Local Inflammatory Response ◽  
Induced Apoptosis ◽  
Deficient Mice

Fas receptor-Fas ligand (FasL) signalling is involved in apoptosis of immune cells as well as of the virus infected target cells but increasing evidence accumulates on Fas as a mediator of apoptosis-independent processes such as induction of activating and proinflammatory signals. In this study, we examined the role of Fas/FasL pathway in inflammatory and antiviral response in lungs using a mousepox model applied to C57BL6/J, B6. MRL-Faslpr/J, and B6Smn.C3-Faslgld/J mice. Ectromelia virus (ECTV) infection of Fas- and FasL-deficient mice led to increased virus titers in lungs and decreased migration of IFN-γexpressing NK cells, CD4+ T cells, CD8+ T cells, and decreased IL-15 expression. The lungs of ECTV-infected Fas- and FasL-deficient mice showed significant inflammation during later phases of infection accompanied by decreased expression of anti-inflammatory IL-10 and TGF-β1 cytokines and disturbances in CXCL1 and CXCL9 expression. Experiments in vitro demonstrated that ECTV-infected cultures of epithelial cells, but not macrophages, upregulate Fas and FasL and are susceptible to Fas-induced apoptosis. Our study demonstrates that Fas/FasL pathway during ECTV infection of the lungs plays an important role in controlling local inflammatory response and mounting of antiviral response.

scholarly journals Contribution of glutaredoxin-1 to Fas s-glutathionylation in ethanol-induced liver injury

2020 ◽  
Author(s):  
Xiaomin Sun ◽  
Qin Deng ◽  
Yunfei Zhang ◽  
Jingyu Chen ◽  
chunbao guo
Keyword(s):  
Liver Injury ◽  
Alcohol Exposure ◽  
Nuclear Factor Κb ◽  
Signaling Cascades ◽  
Alcoholic Liver Injury ◽  
Genetic Ablation ◽  
Induced Apoptosis ◽  
The Impact ◽  
Deficient Mice

Abstract Background The reversible glutathionylation modification (PSSG) of Fas augments apoptosis, which can be reversed by the cytosolic deglutathionylation enzyme glutaredoxin-1 (Grx1), but its roles in alcoholic liver injury remain unknown. Therefore, the objective of this study was to investigate the impact of genetic ablation of Grx1 on Fas-SSG in regulating ethanol-induced injury. Methods The role of Grx1 in alcoholic liver injury was investigated in Grx1 knockout mice. Alcoholic liver injury was achieved by feeding mice with a liquid diet containing 5% ethanol for 2 weeks. Results We demonstrated that ethanol-fed mice had increased Grx1 activity and oxidative damage in the liver. On the other hand, Grx1-deficient mice had more serious liver damage when exposed to ethanol compared to that of wild-type mice, accompanied by increased alanine aminotransferase and aspartate aminotransferase levels, Fas-SSG, cleaved caspase-3 and hepatocyte apoptosis. Grx1 ablation resulted in the suppression of ethanol-induced nuclear factor-κB (NF-κB) signaling, its downstream signal, and Akt signaling cascades, which are required for protection against Fas-mediated apoptosis. Accordingly, blocking NK-κB prevented Fas-induced apoptosis in WT mice but not Grx1-/- mice. Furthermore, the number of Kupffer cells and related proinflammatory cytokines, including Akt, were lower in Grx1-/- livers than those of the controls. Conclusions Grx1 is essential for adaptation to alcohol exposure-induced oxidative injury by modulating Fas-SSG and Fas-induced apoptosis.

MiR-223 is dispensable for platelet production and function in mice

2013 ◽  
Vol 110 (12) ◽  
pp. 1207-1214 ◽  
Author(s):  
Xavier Loyer ◽  
Simon Leierseder ◽  
Tobias Petzold ◽  
Lin Zhang ◽  
Steffen Massberg ◽  
...  
Keyword(s):  
Platelet Adhesion ◽  
Cell Types ◽  
Surface Expression ◽  
Wild Type ◽  
Platelet Production ◽  
Multiple Cell ◽  
And Function ◽  
Deficient Mice ◽  
Platelet Depletion

SummaryMicroRNAs (miRNAs) are key physiological regulators in multiple cell types. Here, we assessed platelet production and function in mice deficient in miR-223, one of the most abundantly expressed miRNAs in platelets and megakaryocytes. We found platelet number, size, lifespan as well as surface expression of platelet adhesion receptors to be unchanged in miR-223-deficient mice. Likewise, loss of miR-223 did not affect platelet activation, adhesion and aggregation and also had no effect on bleeding times. Moreover, miR-223 null megakaryocytes developed normally and were capable to form pro-platelets. However, we detected a transient delay in the recovery of platelet numbers following antibody-induced platelet depletion in miR-223-deficient animals. This delay was not observed after transplantation of bone marrow from miR-223-deficient animals into wild-type recipients, indicating a non-cell-autonomous role of miR-223 for thrombopoiesis. Overall, our data indicate a surprisingly modest role of miR-223 in platelet production, while the function of platelets does not seem to depend on miR-223.

Liver involvement in chronic granulomatous disease: the role of ultrasound in diagnosis and treatment.

Radiology ◽  
1984 ◽  
Vol 153 (1) ◽  
pp. 117-121 ◽  
Author(s):  
L A Garel ◽  
D M Pariente ◽  
C Nezelof ◽  
V J Barral ◽  
C Aboulker ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Diagnosis And Treatment ◽  
Liver Involvement ◽  
Granulomatous Disease
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