Serum Proteins Modified by Neutrophil-Derived Oxidants as Mediators of Neutrophil Stimulation

Körmöczi, Günther F.; Wölfel, Ulrike M.; Rosenkranz, Alexander R.; Hörl, Walter H.; Oberbauer, Rainer; Zlabinger, Gerhard J.

doi:10.4049/jimmunol.167.1.451

Cited by 21 publications

(13 citation statements)

References 70 publications

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“…Activation of normal PMN in vitro and in vivo leads to an increased expression of CD66b, which is mobilized from intracellular granules to the cell membrane (15, 16). In fact, MDSC from RCC patients had an increased expression of CD66b compared with autologous PMN and PMN from controls ( P = 0.0272; Fig.…”

Section: Resultsmentioning

confidence: 99%

Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes

et al. 2009

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Myeloid-derived suppressor cells (MDSC) producing arginase I are increased in the peripheral blood of patients with renal cell carcinoma (RCC). MDSC inhibit T-cell function by reducing the availability of L-arginine and are therefore considered an important tumor escape mechanism. We aimed to determine the origin of arginase I-producing MDSC in RCC patients and to identify the mechanisms used to deplete extracellular L-arginine. The results show that human MDSC are a subpopulation of activated polymorphonuclear (PMN) cells expressing high levels of CD66b, CD11b, and VEGFR1 and low levels of CD62L and CD16. In contrast to murine MDSC, human MDSC do not deplete L-arginine by increasing its uptake but instead release arginase I into the circulation. Activation of normal PMN induces phenotypic and functional changes similar to MDSC and also promotes the release of arginase I from intracellular granules. Interestingly, although activation of normal PMN usually ends with apoptosis, MDSC showed no increase in apoptosis compared with autologous PMN or PMN obtained from normal controls. High levels of VEGF have been shown to increase suppressor immature myeloid dendritic cells in cancer patients. Treatment of RCC patients with anti-VEGF antibody bevacizumab, however, did not reduce the accumulation of MDSC in peripheral blood. In contrast, the addition of interleukin-2 to the treatment increased the number of MDSC in peripheral blood and the plasma levels of arginase I. These results may provide new insights on the mechanisms of tumor-induced anergy/tolerance and may help explain why some immunotherapies fail to induce an antitumor response. [Cancer Res 2009;69(4):1553-60]

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Section: Resultsmentioning

confidence: 99%

Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes

et al. 2009

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“…Activated PMNLs can modify serum proteins via the production of reactive oxygen species. These modified proteins, in turn, bind to and activate PMNLs [175]. Therefore it has been suggested that local PMNL-initiated oxidative alterations of serum proteins may be a general autocrine and paracrine pro-inflammatory enhancer mechanism for PMNL activation and accumulation at the site of inflammation [175].…”

Section: Uremic Toxinsmentioning

confidence: 99%

Immune Dysfunction in Uremia—An Update

Cohen¹,

Hörl²

2012

Toxins

149

137

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Kidney dysfunction leads to disturbed renal metabolic activities and to impaired glomerular filtration, resulting in the retention of toxic solutes affecting all organs of the body. Cardiovascular disease (CVD) and infections are the main causes for the increased occurrence of morbidity and mortality among patients with chronic kidney disease (CKD). Both complications are directly or indirectly linked to a compromised immune defense. The specific coordinated roles of polymorphonuclear leukocytes (PMNLs), monocytes/macrophages, lymphocytes and antigen-presenting cells (APCs) in maintaining an efficient immune response are affected. Their normal response can be impaired, giving rise to infectious diseases or pre-activated/primed, leading to inflammation and consequently to CVD. Whereas the coordinated removal via apoptosis of activated immune cells is crucial for the resolution of inflammation, inappropriately high apoptotic rates lead to a diminished immune response. In uremia, the balance between pro- and anti-inflammatory and between pro- and anti-apoptotic factors is disturbed. This review summarizes the interrelated parameters interfering with the immune response in uremia, with a special focus on the non-specific immune response and the role of uremic toxins.

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“…The difference may be due to the fact that the NADPH oxidase is inactive in resting cells and activation of the NADPH oxidase is a multistep process requiring adequate stimulation of the neutrophil granulocyte [5]. In particular, cell separation and the lack of selected serum proteins may suppress neutrophil respiratory burst [31]. Therefore, we measured respiratory burst in whole blood and cells were stimulated by fMLP or opsonized E. coli, both known to be adequate stimuli [32,33].…”

Section: Discussionmentioning

confidence: 99%

Increased Respiratory Burst and Increased Expression of Complement Receptor-3 (CD11b/CD18) and of IL-8 Receptor-A in Neutrophil Granulocytes from Newborns after Vaginal Delivery

Gessler

Dahinden²

2003

Neonatology

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To study neutrophil activation in cord blood as a function of the mode of delivery, we performed analysis of the function of neutrophil granulocytes by assessing their ability to produce reactive oxygen products (ROP) as well as neutrophil cell surface expression of CD11b/CD18 and interleukin (IL)-8 receptors quantified with flow cytometry. Plasma levels of granulocyte colony-stimulating factor (G-CSF) were measured using an immunoassay. Neutrophil granulocytes were derived from cord blood of term newborns delivered vaginally (n = 20) and by cesarean section (n = 10), and, for comparison, from adult peripheral blood (n = 15). Blood neutrophil counts and the capacity of neutrophil granulocytes to produce ROP in response to stimulation with Escherichia coli was increased in newborns after vaginal delivery as compared to newborns delivered by cesarean section. The level of expression of the adhesion molecule/complement receptor CD11b/CD18 and the chemokine receptor IL-8 RA was also higher after vaginal delivery. Plasma concentrations of G-CSF in cord blood of newborns were higher than those of adults with no difference detectable between vaginal delivery and cesarean section. The data demonstrate a higher functional responsiveness and a higher expression level of functionally important receptors in neutrophils after vaginal delivery possibly due to activation of neutrophil granulocytes during labor.

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Serum Proteins Modified by Neutrophil-Derived Oxidants as Mediators of Neutrophil Stimulation

Cited by 21 publications

References 70 publications

Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes

Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes

Immune Dysfunction in Uremia—An Update

Increased Respiratory Burst and Increased Expression of Complement Receptor-3 (CD11b/CD18) and of IL-8 Receptor-A in Neutrophil Granulocytes from Newborns after Vaginal Delivery

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