Modulation of neutrophil migration by exogenous gaseous nitric oxide

Vanuffelen, B. E.; Koster, Ben M. de; Broek, Peter J.A. Van den; VanSteveninck, John; Elferink, J. G. R.

doi:10.1002/jlb.60.1.94

Cited by 46 publications

(31 citation statements)

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“…inhibition of leukocyte functions including chemotaxis and superoxide generation, especially when these NO donors were used at higher concentrations (25)(26)(27). With respect to degranulation, published reports indicate a biphasic dose response in which NO and cGMP enhance exocytosis at low concentrations and inhibits exocytosis at higher concentrations (48,(57)(58)(59). The inhibitory effect in leukocyte functions may be attributed to the ability of several NO donors and cGMP analogs to stimulate cAMP accumulation when used at high concentrations (60).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Leukocyte Degranulation by cGMP-Dependent Protein Kinase and Phosphoinositide 3-Kinase: Potential Roles in Phosphorylation of Target Membrane SNARE Complex Proteins in Rat Mast Cells

Nanamori

Chen

et al. 2007

The Journal of Immunology

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We examined the roles of cGMP-dependent protein kinase (PKG) and PI3K in degranulation induced by fMLF and by FcεRI cross-linking. In rat basophilic leukemia-2H3 cells expressing formyl peptide receptor, the PKG inhibitors KT5823 and Rp-8-Br-PET-cGMP, as well as the PI3K inhibitor LY294002, reduced agonist-stimulated β-hexosaminidase release in a dose-dependent manner. These inhibitors also abolished vesicular fusion with the plasma membrane, as evidenced by diminished annexin V staining. Agonist-induced degranulation was completely blocked when LY294002 was applied together with one of the PKG inhibitors, suggesting an additive and possibly synergistic effect. In contrast, the PKG inhibitors did not affect fMLF-induced intracellular calcium mobilization and Akt phosphorylation. Likewise, LY294002 did not alter fMLF-induced elevation of intracellular cGMP concentration, and the inhibitory effect of LY294002 was not reversed by a cell-permeable analog of cGMP. Treatment with fMLF induced phosphorylation of soluble N-ethylmaleimide-sensitive factor-attachment protein (SNAP)-23, syntaxins 2, 4, and 6, and Monc18-3. The induced phosphorylation of SNAP-23 and syntaxins 2 and 4 was blocked by Rp-8-Br-PET-cGMP and LY294002. However, LY294002 was less effective in inhibiting Munc18-3 phosphorylation. The induced phosphorylation of syntaxin 6 was not effectively blocked by either Rp-8-Br-PET-cGMP or LY294002. Treatment of human neutrophils with the PKG inhibitors and LY294002 reduced enzyme release from primary, secondary, and tertiary granules. These results suggest that PKG and PI3K are involved in degranulation, possibly through phosphorylation of target membrane SNAP receptor proteins and their binding proteins.

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Section: Discussionmentioning

confidence: 99%

Regulation of Leukocyte Degranulation by cGMP-Dependent Protein Kinase and Phosphoinositide 3-Kinase: Potential Roles in Phosphorylation of Target Membrane SNARE Complex Proteins in Rat Mast Cells

Nanamori

Chen

et al. 2007

The Journal of Immunology

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“…For example, platelet-derived growth factor and other cytosolic proteins that are released by muscle after crush injury [18] can act as chemoattractants to inflammatory cells [19] and contribute to inflammatory cell activation [20]. NO has also been shown to promote motility [21] and chemotaxis [22] of neutrophils, which may contribute to their ability to invade injured tissues.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

Pizza

Hernandez

Tidball

1998

Journal of Leukocyte Biology

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The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1 ؉ and ED2 ؉ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor N -nitro-L-arginine methyl ester (L-NAME) significantly reduced the concentrations of neutrophils, ED1 ؉ and ED2 ؉ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for L-NAME-treated animals compared with watertreated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between L-NAME-treated and control animals, suggesting that L-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells.

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“…The precise function of cGMP-elevating agents and NO donors in regulating neutrophil chemotaxis, granule secretion, and the respiratory burst is controversial (8, 10, 18 -21). NO has diverse effects on neutrophil functions, because a concentration-dependent biphasic effect has been reported for chemotaxis and granule secretion (22)(23)(24). Interestingly, high concentrations of NO-releasing compounds and cGMP analogues inhibit chemotaxis, whereas lower concentrations facilitate this response (20,(22)(23)(24).…”

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confidence: 99%

“…NO has diverse effects on neutrophil functions, because a concentration-dependent biphasic effect has been reported for chemotaxis and granule secretion (22)(23)(24). Interestingly, high concentrations of NO-releasing compounds and cGMP analogues inhibit chemotaxis, whereas lower concentrations facilitate this response (20,(22)(23)(24). Evidence suggests that exogenous NO or L-Arg regulates chemotaxis and granule secretion via a cGKI-dependent mechanism (9,(22)(23)(24)(25).…”

mentioning

confidence: 99%

“…Interestingly, high concentrations of NO-releasing compounds and cGMP analogues inhibit chemotaxis, whereas lower concentrations facilitate this response (20,(22)(23)(24). Evidence suggests that exogenous NO or L-Arg regulates chemotaxis and granule secretion via a cGKI-dependent mechanism (9,(22)(23)(24)(25). cGKI is an established downstream target of the NO/cGMP signaling cascade.…”

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confidence: 99%

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Neutrophil Dysfunction in Guanosine 3′,5′-Cyclic Monophosphate-Dependent Protein Kinase I-Deficient Mice

Werner

Godfrey²,

Arnold³

et al. 2005

The Journal of Immunology

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The regulation of neutrophil functions by Type I cGMP-dependent protein kinase (cGKI) was investigated in wild-type (WT) and cGKI-deficient (cGKI−/−) mice. We demonstrate that murine neutrophils expressed cGKIα. Similar to the regulation of Ca2+ by cGKI in other cells, there was a cGMP-dependent decrease in Ca2+ transients in response to C5a in WT, but not cGKI−/− bone marrow neutrophils. In vitro chemotaxis of bone marrow neutrophils to C5a or IL-8 was significantly greater in cGKI−/− than in WT. Enhanced chemotaxis was also observed with cGKI−/− peritoneal exudate neutrophils (PE-N). In vivo chemotaxis with an arachidonic acid-induced inflammatory ear model revealed an increase in both ear weight and myeloperoxidase (MPO) activity in ear punches of cGKI−/− vs WT mice. These changes were attributable to enhanced vascular permeability and increased neutrophil infiltration. The total extractable content of MPO, but not lysozyme, was significantly greater in cGKI−/− than in WT PE-N. Furthermore, the percentage of MPO released in response to fMLP from cGKI−/− (69%) was greater than that from WT PE-N (36%). PMA failed to induce MPO release from PE-N of either genotype. In contrast, fMLP and PMA released equivalent amounts of lysozyme from PE-N. However, the percentage released was less in cGKI−/− (∼60%) than in WT (∼90%) PE-N. Superoxide release (maximum velocity) revealed no genotype differences in responses to PMA or fMLP stimulation. In summary, these results show that cGKIα down-regulates Ca2+ transients and chemotaxis in murine neutrophils. The regulatory influences of cGKIα on the secretagogue responses are complex, depending on the granule subtype.

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Modulation of neutrophil migration by exogenous gaseous nitric oxide

Cited by 46 publications

References 0 publications

Regulation of Leukocyte Degranulation by cGMP-Dependent Protein Kinase and Phosphoinositide 3-Kinase: Potential Roles in Phosphorylation of Target Membrane SNARE Complex Proteins in Rat Mast Cells

Regulation of Leukocyte Degranulation by cGMP-Dependent Protein Kinase and Phosphoinositide 3-Kinase: Potential Roles in Phosphorylation of Target Membrane SNARE Complex Proteins in Rat Mast Cells

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

Neutrophil Dysfunction in Guanosine 3′,5′-Cyclic Monophosphate-Dependent Protein Kinase I-Deficient Mice

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