Nitric oxide has a role in regulating VLA-4-integrin expression on the human neutrophil cell surface

Conran, Nicola; Gambero, Alessandra; Ferreira, Heloisa H.A.; Antunes, Edson; Nucci, Gilberto De

doi:10.1016/s0006-2952(03)00243-0

Cited by 35 publications

(38 citation statements)

References 47 publications

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“…The surface expression of the VLA-4 integrin subunit, CD49d, was also determined on SCDneu, since the involvement of β1 integrins has been implicated in neutrophil recruitment during chronic inflammation 19 and NO signaling may have a role in controlling VLA-4 integrin expression on the neutrophil cell surface. 9 No significant alteration in CD49d expression was found, however, on the surface of SCDneu. Interestingly, following incubation with 10 µM SNP (30 mins., 37°C), the surface expression of the CD11a subunit was significantly decreased on both SCD and SCDHU neutrophils to levels similar to those of CONneu (Table 1).…”

Section: Resultsmentioning

confidence: 92%

“…Similarly, NO-dependent signaling has been shown to alter platelet GPIIb/IIIa integrin function, as well as neutrophil Mac-1 integrin affinity or avidity. 9,20 Interestingly, the adhesion of neutrophils from SCD individuals on HU therapy (SCDHUneu) demonstrated a significantly lower adhesion to fibronectin and ICAM-1 that approached that of CONneu adhesion (Figure 1). NOx in these cells were not found to be significantly higher than in SCDneu (SCDHUneu; 4.22±0.92 µM/1×10 6 cells; p>0.05; n=11).…”

Section: Resultsmentioning

confidence: 99%

“…inhibiting endothelial adhesion molecule expression 8 and reducing the adhesive properties of leukocytes. 9 At present, hydroxyurea (HU) is the only widely-used therapy for the treatment of SCD, reducing the frequency of vasoocclusive crisis, acute chest syndrome and transfusion, and increasing fetal hemoglobin (HbF) production in erythroid cells. 10 While it has been proposed that HU induces HbF production via tyrosyl radical activation on ribonucleotide reductase, 11 there is evidence to suggest that HU may induce γ-globin gene expression in erythroleukemic cells and primary human erythroblasts via a NO-guanylate cyclase dependent pathway.…”

Section: Introductionmentioning

confidence: 99%

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Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation

Canalli¹,

Franco‐Penteado²,

Saad³

et al. 2008

Haematologica

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Increased leukocyte adhesion to vascular endothelium contributes to vaso-occlusion in sickle cell disease. Since nitric oxide bioavailability is decreased in sickle cell disease and nitric oxide may inhibit leukocyte adhesion, we investigated whether stimulation of NO-signaling pathways can reduce the adhesive properties of neutrophils from sickle cell disease individuals (sickle cell diseaseneu). sickle cell diseaseneu presented greater adhesion in vitro to both fibronectin and ICAM-1 than control neutrophils. Co-incubation of sickle cell diseaseneu with the nitric oxide-donor agents, sodium nitroprusside and dietheylamine NONOate (DEANO), and the guanylate cyclase stimulator, BAY41-2272, all significantly reduced the increased adhesion to fibronectin/ICAM-1. Oxadiazolo[4,3-a]quinoxalin-1-one, a guanylate cyclase inhibitor, reversed sodium nitroprusside/DEANO-diminished adhesion to fibronectin, implicating cGMP-dependent signaling in this mechanism. Interestingly, intracellular cGMP was significantly higher in neutrophils from sickle cell disease individuals on hydroxyurea (sickle cell diseaseHUneu). Accordingly, sickle cell diseaseHUneu adhesion to fibronectin/ICAM-1 was significantly lower than that of sickle cell diseaseneu. Agents that stimulate the nitric oxide/cGMP-dependent pathway may have beneficial effects on leukocyte function if used in these subjects.

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Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation

Canalli¹,

Franco‐Penteado²,

Saad³

et al. 2008

Haematologica

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“…A possible explanation for this discrepancy is that different Abs were used to deplete eosinophils (anti-CD49d in the previous report vs anti-CD9 in our case). In this regard, it is noteworthy that the CD49d Ag is strongly expressed on the surface of neutrophil precursors and moderately on peripheral blood human neutrophils (48,49). It is therefore conceivable that a neutrophil subpopulation that strongly expresses C/EBP is removed when using anti-CD49d Abs to deplete eosinophils.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Cytokine Production by Human Neutrophils Involves C/EBP Transcription Factors

Cloutier

Guindi

Larivée

et al. 2009

The Journal of Immunology

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A growing number of neutrophil-derived cytokines have proven to be crucial to various inflammatory and immune processes in vivo. Whereas C/EBP (CCAAT/enhancer-binding protein) transcription factors are important for neutrophil differentiation from myeloid precursors, we report herein that they also regulate cytokine production in mature neutrophils. All known C/EBP proteins but C/EBP␥ are expressed in neutrophils; most isoforms localize to the nucleus, except for C/EBP␣, which is cytoplasmic. Neutrophil stimulation does not alter the overall levels, cellular distribution, or turnover of C/EBP proteins; it also does not further induce the constitutive DNA-binding activity detected in nuclear extracts, consisting of C/EBP␤ and C/EBP. However, nuclear C/EBP␤ is rapidly phosphorylated upon cell stimulation, suggesting that it can activate cytokine promoters. Indeed, the transactivation of an IL-8 promoter-luciferase construct in a human neutrophil-like cell line was impaired when its C/EBP or NF-B sites were mutated. Overexpression of a C/EBP repressor also impeded IL-8 promoter transactivation, as well as the generation of IL-8, Mip-1␣, and Mip-1␤ in this cellular model, whereas TNF-␣ generation was mostly unaffected. Finally, overexpression of a C/EBP␤ mutant (T235A) as well as chromatin immunoprecipitation assays unveiled an important role for this residue in cytokine induction. This is the first demonstration that C/EBP factors are important regulators of cytokine expression in human neutrophils.

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“…The circu- leukocytes and endothelial cells. 53,54 The loss of response to NO and, consequently, of vascular regulation, was demonstrated using transgenic mice, known as Berkeley (BERK), in which the murine genes for the α and β globins were knocked-out and the human α and β S genes expressed as a transgene. 55 The severity of SCD is modulated by a variety of genetic factors.…”

Section: Pathophysiologymentioning

confidence: 99%

Genética das doenças hematológicas: as hemoglobinopatias hereditárias

Sonati¹,

Costa²

2008

J. Pediatr. (Rio J.)

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Objective: To summarize recently published data on the pathophysiology, diagnosis and treatment of sickle cell diseases and β-Thalassemias, the most relevant hereditary hemoglobinopathies in the global population.Sources: Searches were run on the MEDLINE and SCIELO databases, limited to the period from 2003 to May 2008, using the terms hereditary hemoglobinopathies, sickle cell diseases and β-thalassemia. Two books and two chapters were also included. Summary of the findings:More than 2,000 articles were identified; those providing the most important information and broadest views were selected.Conclusions: Morbidity and mortality rates from sickle cell diseases and β-thalassemia are still very high and represent an important challenge. Increased understanding of pathophysiological aspects has lead to significant improvements in treatment and prevention of these diseases. J Pediatr (Rio J). 2008;84(4 Suppl):S40-51:Hereditary hemoglobinopathies, sickle cell diseases, β-thalassemia.

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Nitric oxide has a role in regulating VLA-4-integrin expression on the human neutrophil cell surface

Cited by 35 publications

References 47 publications

Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation

Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation

Inflammatory Cytokine Production by Human Neutrophils Involves C/EBP Transcription Factors

Genética das doenças hematológicas: as hemoglobinopatias hereditárias

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