Investigation of the role of nitric oxide and cyclic GMP in both the activation and inhibition of human neutrophils

  title={Investigation of the role of nitric oxide and cyclic GMP in both the activation and inhibition of human neutrophils},
  author={Payong Wanikiat and David F. Woodward and Roma A. Armstrong},
  journal={British Journal of Pharmacology},
1 The aim of this study was to establish the role of nitric oxide (NO) and cyclic GMP in chemotaxis and superoxide anion generation (SAG) by human neutrophils, by use of selective inhibitors of NO and cyclic GMP pathways. In addition, inhibition of neutrophil chemotaxis by NO releasing compounds and increases in neutrophil nitrate/nitrite and cyclic GMP levels were examined. The ultimate aim of this work was to resolve the paradox that NO both activates and inhibits human neutrophils. 2 A role… 

Role of cyclic GMP on inhibition by nitric oxide donors of human eosinophil chemotaxis in vitro

This study was designed to investigate the effects of the nitric oxide (NO) donors sodium nitroprusside (SNP), 3‐morpholinosydnonimine (SIN‐1) and S‐nitroso‐N‐acetylpenicillamine (SNAP) on

Nitric oxide regulates neutrophil migration through microparticle formation.

Data show that NO can modulate neutrophil migration by regulating microparticle formation and the ability of L-NAME-induced microparticles to enhance migration was found to be dependent on the number ofmicroparticles produced and not an increase in microp article surface L-selectin or PSGL-1 expression.

Relaxin inhibits the activation of human neutrophils: involvement of the nitric oxide pathway.

Evidence is provided that relaxin inhibits the activation of human neutrophils stimulated by different proinflammatory agents, which could be of relevance in toning down maternal neutrophil activation during pregnancy, thereby counteracting the occurrence of pregnancy-related disorders such as preeclampsia.

Signal transduction pathways affected by nitric oxide donors during neutrophil functional response in vitro

It is concluded that each NO donor depending on its concentration and chemical nature may act on different elements of neutrophil signalling pathways capable of inducing distinct neutrophils functions.

Nitric Oxide Derived from Human Umbilical Vein Endothelial Cells Inhibits Transendothelial Migration of Neutrophils

The findings imply the role of NO constitutively generated by HUVECs in protection against excessive neutrophil extravasation and unnecessary tissue damage under physiological conditions.

Role of nitric oxide in the maturation process of human dendritic cells

The cGMP dependent modulation of DC function reported here is due to a synergism between NO and the various maturation stimuli since neither the changes in endocytic function nor the enhanced T cell activation and IL-12 release were observed after DC exposure to DETA-NO only.



Inhibition of chemotaxis Ng-monomethyl-L-arginine: a role for cyclic GMP.

The hypothesis that the L-arginine metabolism to NO and its effect on the cGMP level may be important for the dynamic changes required for neutrophil chemotaxis is supported.

Inhibition by nitric oxide‐donors of human polymorphonuclear leucocyte functions

The results suggest that NO, possibly through increased cyclic GMP, inhibits the activation of human PMNs and may thus act as a local modulator in inflammatory processes.

Investigation of the inhibitory effects of PGE2 and selective EP agonists on chemotaxis of human neutrophils

  • R. Armstrong
  • Biology, Medicine
    British journal of pharmacology
  • 1995
The hypothesis that cyclic AMP is the second messenger involved in prostaglandin E2‐stimulated human neutrophils is tested, and the inhibitory effects of selective EP agonists and type IV phosphodiesterase (PDE) inhibitors, rolipram and Ro20‐1724 have been examined.

Exogenous nitric oxide elicits chemotaxis of neutrophils in vitro

In vitro experiments indicate that exogenous NO could mediate the chemotaxis of neutrophils and thus suggest that NO could contribute to neutrophil recruitment in vivo.

Regulation of human neutrophil degranulation by LY-83583 and L-arginine: role of cGMP-dependent protein kinase.

The data suggest that activators of neutrophil degranulation mediate this response through a cGMP-dependent protein kinase mechanism that is dependent on the concentration of A-23187 or FMLP.

Modulation of neutrophil migration by exogenous gaseous nitric oxide

It appears that a small change in the level of cytoplasmic free calcium does play a role in the enhancement of random migration by NO, which emphasizes the importance of this second messenger as a modulator of neutrophil functions.

Inhibitors of nitric oxide synthase attenuate human neutrophil chemotaxis in vitro.

The data indicate that nitric oxide synthase inhibitors attenuate chemotaxis of unstimulated and primed polymorphonuclear leukocytes in vitro, suggesting that the L-arginine/nitric oxide biosynthetic pathway plays an important role in regulating polymorphonnuclear leukocyte emigration in vivo.

Peroxynitrite augments fMLP‐stimulated chemiluminescence by neutrophils in human whole blood

LDCL elicited by fMLP in diluted whole blood appears primarily mediated by hypo‐chlorous acid derived from myeloperoxidase; (2) pretreatment with the nitric oxide donor SIN‐1 or with peroxynitrite augments LDCL; and (3) LTB4 release does not contribute to f MLP‐stimulated LDCL or in the modulation of LDCL by SIN•1 or peroxysitrite.

Nitric oxide, an endothelial cell relaxation factor, inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase.

The data suggest that nitric oxide inhibits neutrophil O2+ production via direct effects on membrane components of the NADPH oxidase before the assembly of the activated complex.