Intracellular signaling in neutrophil priming and activation

Downey, Gregory P.; Fukushima, Toshiro; Fialkow, Léa; Waddell, Thomas K.

doi:10.1016/s1043-4682(05)80005-4

Cited by 85 publications

(50 citation statements)

References 52 publications

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“…This partial phosphorylation of p47 phox could be one mechanism by which GM-CSF primes neutrophil respiratory burst. Other candidate-priming mechanisms include increased membrane expression of cytochrome b558 (16,17), increased expression of triggering receptors such as fMLP receptors, activation of heterotrimeric G proteins (18), and other mechanisms (2,3).…”

Section: Tnf-␣ Inducesmentioning

confidence: 99%

TNF-α Induces Phosphorylation of p47phox in Human Neutrophils: Partial Phosphorylation of p47phox Is a Common Event of Priming of Human Neutrophils by TNF-α and Granulocyte-Macrophage Colony-Stimulating Factor

Dewas

Dang

Gougerot‐Pocidalo

et al. 2003

The Journal of Immunology

147

116

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Phosphorylation of p47phox is a key event in NADPH oxidase activation. We examined the ability of proinflammatory cytokines such as TNFα, IL-1, and G-CSF to induce this process compared with GM-CSF. Only TNF-α and GM-CSF induced a clear p47phox phosphorylation. This phosphorylation was time dependent and reached its maximum at 20 min. Two-dimensional phosphopeptide mapping of p47phox phosphorylated in neutrophils primed with TNF-α revealed partial phosphorylation of p47phox on the same peptide as for GM-CSF. Neutrophil incubation with TNF-α and subsequent addition of the chemotactic peptide fMLP resulted in more intense phosphorylation of p47phox sites than with each reagent alone. A neutralizing Ab against the p55 TNF receptor, contrary to a neutralizing Ab against the p75 TNF receptor, inhibited TNF-α-induced p47phox phosphorylation. Neutrophil treatment with both TNF-α and GM-CSF resulted in more intense phosphorylation of the same p47phox peptide observed with each cytokine alone, suggesting that they engaged pathways converging on common serines. This additive effect was also obtained on the priming of NADPH oxidase activity. The use of protein kinase inhibitors pointed to the involvement of a protein tyrosine kinase, but not protein kinase C. These findings show that TNF-α, via its p55 receptor, induces a protein tyrosine kinase-dependent selective phosphorylation of p47phox on specific serines. The ability of TNF-α and GM-CSF, two different cytokines with two different receptors to induce this specific p47phox phosphorylation, suggests that this event could be a common element of the priming of neutrophils by TNF-α and GM-CSF.

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Section: Tnf-␣ Inducesmentioning

confidence: 99%

TNF-α Induces Phosphorylation of p47phox in Human Neutrophils: Partial Phosphorylation of p47phox Is a Common Event of Priming of Human Neutrophils by TNF-α and Granulocyte-Macrophage Colony-Stimulating Factor

Dewas

Dang

Gougerot‐Pocidalo

et al. 2003

The Journal of Immunology

147

116

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“…Neutrophil O 2 • -production can be potentiated by prior exposure to "priming" agents such as the proinflammatory cytokines GM-CSF, TNF-a, and IL-8 (20,21). These cytokines inherently induce a very weak oxidative response by neutrophils, but they strongly enhance neutrophil release of ROS on exposure to a secondary applied stimulus such as bacterial N-formyl peptides (22,23).…”

Section: Introductionmentioning

confidence: 99%

A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites

Dang

Stensballe

Boussetta

et al. 2006

Journal of Clinical Investigation

290

281

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“…One way in which this is thought to occur is through a form of signal integration in which prior exposure to local proinflammatory factors is necessary for maximal activation by subsequent oxidase-triggering signals. [13][14][15][16][17] One of best studied examples of this "priming" phenomenon is the ability of tumor necrosis factor-␣ (TNF-␣), a cytokine released primarily by macrophages, to dramatically augment the oxidase response to bacterially derived peptides (eg, N-formyl-methionyl-leucylphenylalanine [fMLP]) or components of the complement cascade (C5a). Indeed it is thought that failure to limit priming of the oxidase may play a key role in pathologic conditions in which inflammation is not effectively resolved, such as in acute respiratory distress syndrome (ARDS) or joint involvement in rheumatoid arthritis.…”

Section: Introductionmentioning

confidence: 99%

Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils

Condliffe

Davidson

Anderson

et al. 2005

Blood

268

275

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It is well established that preexposure of human neutrophils to proinflammatory cytokines markedly augments the production of reactive oxygen species (ROS) to subsequent stimuli. This priming event is thought to be critical for localizing ROS to the vicinity of the inflammation, maximizing their role in the resolution of the inflammation, and minimizing the damage to surrounding tissue. We have used a new generation of isoform-selective phosphoinositide 3-kinase (PI3K) inhibitors to show that ROS production under these circumstances is regulated by temporal control of class I PI3K activity. Stimulation of tumor necrosis factor-␣ (TNF-␣)-primed human neutrophils with N-formylmethionyl-leucyl-phenylalanine (fMLP) results in biphasic activation of PI3K; the first phase is largely dependent on PI3K␥, and the second phase is largely dependent on PI3K␦. The second phase of PI3K activation requires the first phase; it is this second phase that is augmented by TNF-␣ priming and that regulates parallel activation of ROS production. Surprisingly, although TNF-␣-primed mouse bone marrow-derived neutrophils exhibit superficially similar patterns of PI3K activation and ROS production in response to fMLP, these responses are substantially lower and largely dependent on PI3K␥ alone. These results start to define which PI3K isoforms are responsible for modulating neutrophil responsiveness to infection and inflammation. IntroductionNeutrophils are critical components of the immune system and have a vital role in combating bacterial and fungal infections. 1 A key weapon in the neutrophil armory is the so-called "respiratory burst," the generation of reactive oxygen species (ROS) by a multicomponent oxidase complex. 2,3 Patients with chronic granulomatous disease (CGD) caused by defective expression of active oxidase components experience recurrent, life-threatening infections. 4 The role of ROS in fighting infections is complex. ROS are involved in the killing process directly through the damaging actions of oxygen radicals and their halogenated derivatives and indirectly through the activation of phagosomal proteases. [5][6][7] It is also becoming apparent that ROS may regulate the neutrophil lifespan, modify the extracellular matrix through which the neutrophils migrate, and modulate the function of other cells participating in the inflammatory response. [8][9][10][11][12] Given the potential for self-damage, a key feature of the inflammatory response is to confine ROS generation in time and space to areas where it is required. One way in which this is thought to occur is through a form of signal integration in which prior exposure to local proinflammatory factors is necessary for maximal activation by subsequent oxidase-triggering signals. [13][14][15][16][17] One of best studied examples of this "priming" phenomenon is the ability of tumor necrosis factor-␣ (TNF-␣), a cytokine released primarily by macrophages, to dramatically augment the oxidase response to bacterially derived peptides (eg, N-formyl-methionyl-leucylphenylal...

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Intracellular signaling in neutrophil priming and activation

Cited by 85 publications

References 52 publications

TNF-α Induces Phosphorylation of p47phox in Human Neutrophils: Partial Phosphorylation of p47phox Is a Common Event of Priming of Human Neutrophils by TNF-α and Granulocyte-Macrophage Colony-Stimulating Factor

TNF-α Induces Phosphorylation of p47phox in Human Neutrophils: Partial Phosphorylation of p47phox Is a Common Event of Priming of Human Neutrophils by TNF-α and Granulocyte-Macrophage Colony-Stimulating Factor

A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites

Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils

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