Hypoxia prolongs neutrophil survival in vitro

Hannah, Sharon; Mecklenburgh, Kathryn; Rahman, Irfan; Bellingan, Geoffrey; Greening, A P; Haslett, Christopher; Chilvers, Edwin R.

doi:10.1016/0014-5793(95)00986-j

Cited by 191 publications

(136 citation statements)

References 43 publications

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“…A mitochondrial contribution to this activity cannot be ruled out. Finally, it is established that neutrophil-derived reactive oxidant species can regulate the progression of these cells into apoptosis (45)(46)(47). Oxidants derived from either NADPH oxidase or mitochondria may be involved in this process.…”

Section: Discussionmentioning

confidence: 99%

The Mitochondrial Network of Human Neutrophils: Role in Chemotaxis, Phagocytosis, Respiratory Burst Activation, and Commitment to Apoptosis

Fossati

Moulding

Spiller

et al. 2003

The Journal of Immunology

314

251

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It is commonly assumed that human neutrophils possess few, if any, functional mitochondria and that they do not depend on these organelles for cell function. We have used the fluorescent mitochondrial indicators, JC-1, MitoTracker Red, and dihydrorhodamine 123 to show that live neutrophils possess a complex mitochondrial network that extends through the cytoplasm. The membrane potential of these mitochondria was rapidly (within 2 min) disrupted by the addition of FCCP (IC50 = 20 nM), but not by the Fo-ATPase inhibitor, oligomycin (at up to 7 μg/ml). However, inhibition of mitochondrial function with both agents resulted in cell shape changes. Neither activation of the respiratory burst nor phagocytosis of either latex particles or serum-opsonized Staphylococcus aureus was affected by the addition of FCCP or oligomycin. However, FCCP inhibited chemotaxis at concentrations that paralleled disruption of mitochondrial membrane potential. Furthermore, prolonged (2-h) incubation with oligomycin resulted in an impaired ability to activate a respiratory burst and also inhibited chemotaxis. These observations indicate that intact mitochondrial function is required to sustain some neutrophil functions, but not for the rapid initiation of the respiratory burst or phagocytosis. Loss of mitochondrial membrane potential was a very early marker for commitment of neutrophils into apoptosis and preceded the appearance of phosphatidylserine on the cell surface. However, inhibition of mitochondrial function did not accelerate the rate of neutrophil apoptosis. These data shed important insights into the hitherto unrecognized importance of mitochondria in the function of neutrophils during infection and inflammation.

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Section: Discussionmentioning

confidence: 99%

The Mitochondrial Network of Human Neutrophils: Role in Chemotaxis, Phagocytosis, Respiratory Burst Activation, and Commitment to Apoptosis

Fossati

Moulding

Spiller

et al. 2003

The Journal of Immunology

314

251

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show abstract

“…In addition, constitutive neutrophil apoptosis is delayed under hypoxic conditions (46) and in neutrophils from chronic granulomatous disease patients (45). ROI production is not, however, inevitably linked to acceleration of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Induction of Neutrophil Apoptosis by thePseudomonas aeruginosaExotoxin Pyocyanin: A Potential Mechanism of Persistent Infection

Usher

Lawson

Geary³

et al. 2002

The Journal of Immunology

201

173

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Pseudomonas aeruginosa colonizes and infects human tissues, although the mechanisms by which the organism evades the normal, predominantly neutrophilic, host defenses are unclear. Phenazine products of P. aeruginosa can induce death in Caenorhabditis elegans. We hypothesized that phenazines induce death of human neutrophils, and thus impair neutrophil-mediated bacterial killing. We investigated the effects of two phenazines, pyocyanin and 1-hydroxyphenazine, upon apoptosis of neutrophils in vitro. Pyocyanin induced a concentration- and time-dependent acceleration of neutrophil apoptosis, with 50 μM pyocyanin causing a 10-fold induction of apoptosis at 5 h (p < 0.001), a concentration that has been documented in sputum from patients colonized with P. aeruginosa. 1-hydroxyphenazine was without effect. In contrast to its rapid induction of neutrophil apoptosis, pyocyanin did not induce significant apoptosis of monocyte-derived macrophages or airway epithelial cells at time points up to 24 h. Comparison of wild-type and phenazine-deleted strains of P. aeruginosa showed a highly significant reduction in neutrophil killing by the phenazine-deleted strain. In clinical isolates of P. aeruginosa pyocyanin production was associated with a proapoptotic effect upon neutrophils in culture. Pyocyanin-induced neutrophil apoptosis was not delayed either by treatment with LPS, a powerfully antiapoptotic bacterial product, or in neutrophils from cystic fibrosis patients. Pyocyanin-induced apoptosis was associated with rapid and sustained generation of reactive oxygen intermediates and subsequent reduction of intracellular cAMP. Treatment of neutrophils with either antioxidants or synthetic cAMP analogues significantly abrogated pyocyanin-induced apoptosis. We conclude that pyocyanin-induced neutrophil apoptosis may be a clinically important mechanism of persistence of P. aeruginosa in human tissue.

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“…One characteristic feature of advanced solid tumors is hypoxia. In fact, hypoxia promotes HIF-1a-dependent neutrophil survival (44,45) but impairs the respiratory burst activity in human neutrophils (46). In addition, it has been reported that blockade of TGFb in the tumor microenvironment drives neutrophil polarization from a protumoral "N2" phenotype to an antitumoral "N1" phenotype characterized by enhanced cytotoxic and immunostimulatory activities (47).…”

Section: Ly6gmentioning

confidence: 99%

The Complex Role of Neutrophils in Tumor Angiogenesis and Metastasis

Liang

Ferrara

2016

Cancer Immunology Research

298

224

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Chronic inflammation fosters cancer development and progression and also modulates tumor responses to anticancer therapies. Neutrophils are key effector cells in innate immunity and are known to play a critical role in various inflammatory disorders. However, the functions of neutrophils in cancer pathogenesis have been largely neglected until recently and still remain poorly characterized compared with other immune cells in the tumor microenvironment. We highlight recent findings on the mechanisms by which tumor cells, in cooperation with tumorassociated stromal cells, induce expansion, recruitment, and polarization of neutrophils. We also review the multifaceted roles that neutrophils play in different aspects of cancer development and progression, with an emphasis on tumor angiogenesis and metastasis.

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Hypoxia prolongs neutrophil survival in vitro

Cited by 191 publications

References 43 publications

The Mitochondrial Network of Human Neutrophils: Role in Chemotaxis, Phagocytosis, Respiratory Burst Activation, and Commitment to Apoptosis

The Mitochondrial Network of Human Neutrophils: Role in Chemotaxis, Phagocytosis, Respiratory Burst Activation, and Commitment to Apoptosis

Induction of Neutrophil Apoptosis by thePseudomonas aeruginosaExotoxin Pyocyanin: A Potential Mechanism of Persistent Infection

The Complex Role of Neutrophils in Tumor Angiogenesis and Metastasis

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