Induction of human neutrophil apoptosis by nitric oxide donors: evidence for a caspase-dependent, cyclic-GMP-independent, mechanism

Ward, Carol; Wong, Terence H.; Murray, Joanna; Rahman, Irfan; Haslett, Christopher; Chilvers, Edwin R.; Rossi, Adriano G.

doi:10.1016/s0006-2952(99)00329-9

Cited by 96 publications

(66 citation statements)

References 42 publications

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“…Of note and in concordance with viability results (see above), long-lived neutrophils lacked morphological alterations of apoptosis such as chromatin condensation and nuclear pyknosis. 36 Transmission electron micrographs of freshly isolated neutrophils (Figure 2a) and long-lived neutrophils (Figure 2b) showed similar morphology of plasma membranes, intra-cytoplasmic organites and nuclear segmentation.…”

Section: Morphology Of Long-lived Neutrophilsmentioning

confidence: 81%

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

Chakravarti

Rusu

Flamand

et al. 2009

Laboratory Investigation

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Essential cells of innate immunity, neutrophils are often considered to be a homogenous population of terminally differentiated cells. During inflammation, neutrophils are extravasated cells exposed to local factors that prolong their survival and activate their production of mediators implicated in disease progression. In this study, a phenotypically distinct subset of human neutrophils that appear after prolonged exposure to cytokines was characterized. Freshly isolated neutrophils from healthy donors were incubated with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-a and interleukin (IL)-4, three cytokines that are locally present in various inflammatory conditions. Eight to 17% of neutrophils survived beyond 72 h. This subset of non-apoptotic neutrophils, as evaluated by three different markers, was enriched by discontinuous Percoll gradient centrifugation before studying their phenotype. These viable neutrophils showed neoexpression of HLA-DR, CD80 and CD49d. Compared with freshly isolated neutrophils, they responded differentially to second signals similar to formyl-methionyl-leucyl-phenylalanine with three-to four-fold increases in production of superoxide anions and leukotrienes. These cells augmented their phagocytic index by 141%, increased their adhesion to human primary fibroblasts, but reduced their migration in response to chemotactic stimuli and decreased exocytosis of primary and secondary granules. In addition, they produced substantial amounts of IL-8, IL-1Ra and IL-1b. This neutrophil subset had a unique profile of phosphorylation of intracellular signaling molecules. In conclusion, the present identification of a novel neutrophil phenotype highlights the reprogammable character of the neutrophil. This aspect is crucial for our understanding of its contribution to disease pathogenesis and host defense.

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Section: Morphology Of Long-lived Neutrophilsmentioning

confidence: 81%

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

Chakravarti

Rusu

Flamand

et al. 2009

Laboratory Investigation

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“…An induction of neutrophil apoptosis has also been observed using both traditional NO donors such as SNP 44 and different sources of NO such as GSNO (0.5-5 mM). 45 Blaylock et al 46 reported that GEA 3162 (10 mM) increased neutrophil apoptosis as assessed by annexin V binding to exposed phosphatidylserine (PS) at 4 and 8 h, but not at 16 h. On the other hand, the ONOO À donor, SIN-1 (1 mM), showed no significant increase in PS exposure compared to control cells, although there was a small enhancement of annexin V binding at 4 h. The effects of these two compounds were also studied by Ward et al, 10 who demonstrated that concentrations of 10-100 mM GEA 3162 and 0.3-3 mM SIN-1 enhanced caspase-dependent morphological neutrophil apoptosis at 6 and 20 h, and 30-100 mM GEA 3162 increased annexin V binding at 6 h. In contrast to Blaylock's study, however, the increase in morphological apoptosis by 10 mM GEA 3162 was not significant at 6 h, whereas Blaylock observed significant differences at just 4 h. The principal methodological difference between the two studies is in the culture conditions. It has previously been demonstrated that the microenvironment, including cell density and concentration of plasma proteins, has a critical effect on the rate of neutrophil apoptosis in vitro.…”

Section: Neutrophilsmentioning

confidence: 87%

“…However, it is known that NO induces a rise in cGMP in neutrophils through activation of sGC. 8,83 Given that the cell permeable analogues of cAMP (db-cAMP) and cGMP (db-cGMP) can delay constitutive neutrophil apoptosis, 10 and that a rise in cGMP has been postulated to at least partially account for NOmediated inhibition of apoptosis in other cell types, 84,85 it is possible that an increase in one or other of these cyclic nucleotides mediates the inhibition of apoptosis in neutrophils exposed to low concentrations of NO. A role for cyclic nucleotide (cGMP or cAMP) signalling has also been proposed in NO-mediated inhibition of both constitutive and Fas-triggered eosinophil apoptosis.…”

Section: Antiapoptotic Mechanismsmentioning

confidence: 99%

“…Studies have shown that apoptosis in neutrophils and macrophages proceeds via activation of caspase protease enzymes, 10,112,113 part of the classical apoptotic effector cascade. However, the upstream mechanisms by which exposure to NO causes these enzymes to become activated has not been clarified, although several theories have been suggested.…”

Section: Proapoptotic Mechanismsmentioning

confidence: 99%

“…7 NO is capable of inducing inflammatory cell apoptosis and also possesses several other anti-inflammatory properties, including direct downregulation of leukocyte functions, such as neutrophil and monocyte adhesion, and neutrophil chemotaxis, degranulation and superoxide anion (O 2 À ) generation. [8][9][10] It also acts to maintain the impermeable nature of the vascular endothelium to leukocytes. 9 Thus, manipulation of NO concentrations is a particularly promising candidate to alter leukocyte function and rates of apoptosis in inflammatory conditions.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis

et al. 2003

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Apoptosis of inflammatory cells is a critical event in the resolution of inflammation, as failure to undergo this form of cell death leads to increased tissue damage and exacerbation of the inflammatory response. Many factors are able to influence the rate of apoptosis in neutrophils, eosinophils, monocytes and macrophages. Among these is the signalling molecule nitric oxide (NO), which possesses both anti-and proapoptotic properties, depending on the concentration and flux of NO, and also the source from which NO is derived. This review summarises the differential effects of NO on inflammatory cell apoptosis and outlines potential mechanisms that have been proposed to explain such actions.

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Nitric oxide inhibits endothelial cell apoptosis by inhibiting cysteine‐dependent SOD1 monomerization

Peng

Zhang

et al. 2022

FEBS Open Bio

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Endothelial cell apoptosis is an important pathophysiology in many cardiovascular diseases. The gasotransmitter nitric oxide (NO) is known to regulate cell survival and apoptosis. However, the mechanism underlying the effect of NO remains unclear. In this research, by targeting cytosolic copper/zinc superoxide dismutase (SOD1) monomerization, we aimed to explore how NO inhibited endothelial cell apoptosis. We showed that treatment with the NO synthase (NOS) inhibitor nomega‐nitro‐l‐arginine methyl ester hydrochloride (L‐NAME) significantly decreased the endogenous NO content of endothelial cells, facilitated the formation of SOD1 monomers, inhibited dismutase activity, and promoted reactive oxygen species (ROS) accumulation in human umbilical vein endothelial cells (HUVECs); by contrast, supplementation with the NO donor sodium nitroprusside (SNP) upregulated NO content, prevented the formation of SOD1 monomers, enhanced dismutase activity, and reduced ROS accumulation in L‐NAME‐treated HUVECs. Mechanistically, tris(2‐carboxyethyl) phosphine hydrochloride (TCEP), a specific reducer of cysteine thiol, increased SOD1 monomer formation, thus preventing the NO‐induced increase in dismutase activity and the decrease in ROS. Furthermore, SNP inhibited HUVEC apoptosis caused by the decrease in endogenous NO, whereas TCEP abolished this protective effect of SNP. In summary, our data reveal that NO protects endothelial cells against apoptosis by inhibiting cysteine‐dependent SOD1 monomerization to enhance SOD1 activity and inhibit oxidative stress.

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Induction of human neutrophil apoptosis by nitric oxide donors: evidence for a caspase-dependent, cyclic-GMP-independent, mechanism

Cited by 96 publications

References 42 publications

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

Reprogramming of a subpopulation of human blood neutrophils by prolonged exposure to cytokines

Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis

Nitric oxide inhibits endothelial cell apoptosis by inhibiting cysteine‐dependent SOD1 monomerization

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