No detectable NO synthesis from L-arginine or NG-hydroxy-L-arginine in fMLP-stimulated human blood neutrophils despite production of nitrite, nitrate, and citrulline from NG-hydroxy-L-arginine

Holm, Päivi; Kankaanranta, Hannu; Oja, Simo S.; Knowles, Richard G.; Moilanen, Eeva

doi:10.1002/jlb.66.1.127

Cited by 21 publications

(18 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4a). These observations are consistent with previous investigators who have reported that NO production by human blood neutrophils is not influenced by fMLP or by inhibitors of NOS activity (Holm et al 1999;Padgett and Pruett 1995). In contrast, Schmidt et al (1989) reported increased neutrophil-derived NO after fMLP stimulation.…”

Section: Contribution Of Rnssupporting

confidence: 94%

“…Human neutrophils are capable of producing relatively high concentrations of ROS (Rosen et al 1995) and have been demonstrated to cause injury to a variety of cell types (Entman et al 1992;Murphy et al 1999), including cultured skeletal muscle (Pizza et al 2001). Although controversial, human neutrophils appear to lack nitric oxide synthase (NOS) activity (Yan et al 1994) and the ability to produce nitric oxide (NO) (Holm et al 1999;Miles et al 1995;Sethi and Dikshit 2000;Yan et al 1994). On the other hand, human skeletal muscle is known to express high levels of neuronal NOS (nNOS) (Frandsen et al 1996;Nakane et al 1993) and to increase production of NO after contraction-induced muscle injury (Radak et al 1999).…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Deferoxamine reduces and nitric oxide synthase inhibition increases neutrophil-mediated myotube injury

McLoughlin

Tsivitse

Edwards

et al. 2003

Cell and Tissue Research

View full text Add to dashboard Cite

We tested the contribution of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the beta 2 integrin CD18 to neutrophil-mediated myotube injury. Human myotubes were cultured with human neutrophils in the presence or absence of inhibitors directed against ROS, RNS, and CD18. Muscle injury was assessed by a (51)Cr release assay. The inclusion of superoxide dismutase (50-500 U/ml) in the culture medium did not affect myotube injury. A significant protective effect was provided by including catalase (600-2400 U/ml), deferoxamine (1-2 mM), or anti-CD18 antibody (10 microg/ml) in the culture medium. S-Ethylisothiourea (500-1000 microM), an inhibitor of nitric oxide synthase (NOS), significantly increased myotube injury and reduced nitric oxide (NO) in cultures consisting of only myotubes. In conclusion, neutrophil-mediated skeletal muscle injury appears to be largely dependent on CD18-mediated neutrophil adhesion and iron-dependent hydroxyl radical production. In addition, skeletal muscle NOS activity may protect skeletal muscle against the injury caused by neutrophils.

show abstract

Section: Contribution Of Rnssupporting

confidence: 94%

Section: Introductionmentioning

confidence: 97%

Deferoxamine reduces and nitric oxide synthase inhibition increases neutrophil-mediated myotube injury

McLoughlin

Tsivitse

Edwards

et al. 2003

Cell and Tissue Research

View full text Add to dashboard Cite

show abstract

“…Similar phenomenon have been observed in platelets, in which cAMP-dependent protein kinase (PKA) is largely responsible for the inhibition of platelet activation while PKG plays a stimulatory role under several conditions, both in vitro and in vivo (61,62). In neutrophils, fMLF induces a moderate increase in NO and intracellular cGMP concentration as compared with the increases invoked by most NO donors (48), most likely because of the low NOS expression level in the terminally differentiated granulocytes (63,64). The small increase in intracellular cGMP is associated with enhanced neutrophil functions such as degranulation and chemotaxis (48).…”

Section: Discussionmentioning

confidence: 56%

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

View full text Add to dashboard Cite

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.

show abstract

“…Moreover, addition of hydrogen peroxide to Nv-hydroxy-L-arginine in a cell free system also resulted in nitrite release. Finally, recent data demonstrated that denitrification Nv-hydroxy-L-arginine by human neutrophils does not release NO but directly leads to nitrite/nitrate formation instead [17]. Interestingly, NAGASE et al [18] showed that hydrogen peroxide also releases NO from L-arginine, as confirmed by chemiluminescence.…”

Section: Discussionmentioning

confidence: 95%

l-Arginine is not the limiting factor for nitric oxide synthesis by human alveolar macrophagesin vitro

et al. 2001

View full text Add to dashboard Cite

Unlike murine mononuclear phagocytes, human macrophages do not release high amounts of nitric oxide (NO) in vitro despite the presence of nitric oxide synthase (NOS). To determine whether this limited NO synthesis in vitro is due to limited availability of the NOS substrate L-arginine, and putative NOS inhibiting factors present in foetal serum preparations, both alveolar macrophages (AM) and monocyte derived macrophages (MDM) were incubated in various circumstances.Nitrite production measured using stimulated AM was typically v5 pmol?min -1 ?10cells.A range of stimuli were tested, but without result. Furthermore, incubation of MDMs with normal human serum or purified bovine serum albumin instead of foetal calf serum failed to enhance NO production. Moreover, neither the use of arginase inhibitors nor the addition of surplus L-arginine resulted in an increased NO synthesis. Interestingly, addition of the NOS intermediate Nv-hydroxy-L-arginine (100 mM) to AM led to nitrite release, which was unaffected by the NOS inhibitor amino guanidine showing that this effect is NOS independent. It is concluded that the limited nitric oxide production of human macrophages in vitro can neither be explained by limited availability of L-arginine, nor by nitric oxide synthase inhibiting substances in foetal serum. Furthermore, it is shown that nitrite release from Nv-hydroxy-L-arginine by alveolar macrophages is nitric oxide synthase independent.

show abstract

No detectable NO synthesis from L-arginine or NG-hydroxy-L-arginine in fMLP-stimulated human blood neutrophils despite production of nitrite, nitrate, and citrulline from NG-hydroxy-L-arginine

Cited by 21 publications

References 40 publications

Deferoxamine reduces and nitric oxide synthase inhibition increases neutrophil-mediated myotube injury

Deferoxamine reduces and nitric oxide synthase inhibition increases neutrophil-mediated myotube injury

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

l-Arginine is not the limiting factor for nitric oxide synthesis by human alveolar macrophagesin vitro

Contact Info

Product

Resources

About