Hydroxyl Radical as a Potential Intracellular Mediator of Polymorphonuclear Neutrophil Apoptosis

Rollet-Labelle, Emmanuelle; Grange, Marie‐José; Elbim, Carole; Marquetty, Claude; Gougerot‐Pocidalo, Marie‐Anne; Pasquier, Claude

doi:10.1016/s0891-5849(97)00292-x

Cited by 210 publications

(109 citation statements)

References 43 publications

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“…There are numerous reports in the literature showing that oxidants kill cells by inducing apoptosis (12,15,(45)(46)(47)(48), and induction of oxidative stress is often proposed as a common mechanism whereby diverse agents induce apoptosis (13,17,49). Our results (this report and Ref.…”

Section: Modes Of Cell Death Induced In Burkitt's Lymphoma Cells By Vsupporting

confidence: 71%

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Lee

Shacter

1999

Journal of Biological Chemistry

253

215

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Apoptosis and necrosis are two forms of cell death that are induced under different conditions and that differ in morphological and biochemical features. In this report, we show that, in the presence of oxidative stress, human B lymphoma cells are unable to undergo apoptosis and die instead by a form of necrosis. This was established using the chemotherapy drug VP-16 or the calcium ionophore A23187 to induce apoptosis in Burkitt's lymphoma cell lines and by measuring classical markers of apoptotic death, including cell morphology, annexin V binding, DNA ladder formation, and caspase activation. In the presence of relatively low levels of H 2 O 2 (75-100 M), VP-16 and A23187 were unable to induce apoptosis in these cells. Instead, the cells underwent non-apoptotic cell death with mild cytoplasmic swelling and nuclear shrinkage, similar to the death observed when they were treated with H 2 O 2 alone. We found that H 2 O 2 inhibits apoptosis by depleting the cells of ATP. The effects of H 2 O 2 can be overcome by inhibitors of poly(ADP)-ribosylation, which also preserve cellular ATP levels, and can be mimicked by agents such as oligomycin, which inhibit ATP synthesis. The results show that oxidants can manipulate cell death pathways, diverting the cell away from apoptosis. The potential physiological ramifications of this finding will be discussed.

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Section: Modes Of Cell Death Induced In Burkitt's Lymphoma Cells By Vsupporting

confidence: 71%

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Lee

Shacter

1999

Journal of Biological Chemistry

253

215

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“…GO is a H 2 O 2 -generating enzyme that can be used to continuously produce H 2 O 2 in the cell culture environment (37). We found that a 72-h incubation of normal NK cells in the presence of GO (100 ng/ml) significantly reduced NKG2D surface expression ( p Ͻ 0.01) but sMICA alone (data not shown) or in association with glucose oxidase had no effect on NKG2D down-modulation (Fig.…”

Section: Ros Are Major Effectors Responsible For Decreased Nkg2d Exprmentioning

confidence: 78%

Oxidative Stress Mediates a Reduced Expression of the Activating Receptor NKG2D in NK Cells from End-Stage Renal Disease Patients

Péraldi

Berrou

Dulphy

et al. 2009

The Journal of Immunology

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To characterize the immune defect of patients with end-stage renal disease (ESRD), we performed NK cell subset analysis in 66 patients with ESRD treated by hemodialysis (n = 59) or peritoneal dialysis (n = 7). Compared with healthy blood donors, patients undergoing chronic dialysis showed a profound decrease in NKG2D+ cells within both the CD8+ T cell (58% vs 67%, p = 0.03) and NK cell (39% vs 56%, p = 0.002) populations. CD56dim cells, which comprise the majority of NK cells in the periphery, were more affected in this regard than were CD56bright cells. Uremic serum could decrease NKG2D expression on NK cells from healthy donors. Among factors that could contribute to the decrease in NKG2D expression in ESRD patients, reactive oxygen species (ROS) play a major role. We found that catalase could reverse the effects of uremic serum on NKG2D expression (p < 0.001) and that ROS down-regulated NKG2D at the mRNA level and at the NK cell surface. Additionally, ESRD patients had both increased membrane-bound MHC class I-related chain A (MICA) on monocytes (p = 0.04) and increased soluble MICA (203 pg/ml vs 110 pg/ml; p < 0.001). Both ROS and uremic serum could significantly increase in vitro the expression of the NKG2D ligand MICA on the renal epithelial cell line HK-2. Taken together, these studies suggest for the first time that both low NKG2D expression and up-regulation of its ligand MICA are related to ROS production and may be involved in the immune deficiency of ESRD patients.

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“…We capitalized on the low constitutive abundance of Oxidized PS is an essential phagocytic signal VA Tyurin et al oxidizable PS in HL60 cells to understand the importance of cell surface PSox presentation to engulfment by macrophages. We elected to use H 2 O 2 to induce apoptosis 27 in naive HL60 cells (low in oxidizable PS) and LA-HL60 cells (high in oxidizable PS). We were able to demonstrate that accumulation of PSox in apoptotic LA-HL60, but not naive HL60 cells, was associated with their remarkably enhanced phagocytosis by RAW264.7-and THP-1-derived macrophages.…”

Section: Resultsmentioning

confidence: 99%

Oxidatively modified phosphatidylserines on the surface of apoptotic cells are essential phagocytic ‘eat-me’ signals: cleavage and inhibition of phagocytosis by Lp-PLA2

et al. 2014

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Diversified anionic phospholipids, phosphatidylserines (PS), externalized to the surface of apoptotic cells are universal phagocytic signals. However, the role of major PS metabolites, such as peroxidized species of PS (PSox) and lyso-PS, in the clearance of apoptotic cells has not been rigorously evaluated. Here, we demonstrate that H 2 O 2 was equally effective in inducing apoptosis and externalization of PS in naive HL60 cells and in cells enriched with oxidizable polyunsaturated species of PS (supplemented with linoleic acid (LA)). Despite this, the uptake of LA-supplemented cells by RAW264.7 and THP-1 macrophages was more than an order of magnitude more effective than that of naive cells. A similar stimulation of phagocytosis was observed with LA-enriched HL60 cells and Jurkat cells triggered to apoptosis with staurosporine. This was due to the presence of PSox on the surface of apoptotic LA-supplemented cells (but not of naive cells). This enhanced phagocytosis was dependent on activation of the intrinsic apoptotic pathway, as no stimulation of phagocytosis occurred in LA-enriched cells challenged with Fas antibody. Incubation of apoptotic cells with lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), a secreted enzyme with high specificity towards PSox, hydrolyzed peroxidized PS species in LA-supplemented cells resulting in the suppression of phagocytosis to the levels observed for naive cells. This suppression of phagocytosis by Lp-PLA 2 was blocked by a selective inhibitor of Lp-PLA 2 , SB-435495. Screening of possible receptor candidates revealed the ability of several PS receptors and bridging proteins to recognize both PS and PSox, albeit with diverse selectivity. We conclude that PSox is an effective phagocytic 'eat-me' signal that participates in the engulfment of cells undergoing intrinsic apoptosis.

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Hydroxyl Radical as a Potential Intracellular Mediator of Polymorphonuclear Neutrophil Apoptosis

Cited by 210 publications

References 43 publications

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Oxidative Stress Mediates a Reduced Expression of the Activating Receptor NKG2D in NK Cells from End-Stage Renal Disease Patients

Oxidatively modified phosphatidylserines on the surface of apoptotic cells are essential phagocytic ‘eat-me’ signals: cleavage and inhibition of phagocytosis by Lp-PLA2

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