Expression and release of angiopoietin-1 from human neutrophils: Intracellular mechanisms

Neagoe, Paul‐Eduard; Brkovic, Alexandre; Hajjar, Fadi; Sirois, Martin G.

doi:10.1080/08977190903155043

Cited by 18 publications

(27 citation statements)

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“…The release of Ang1 protein from neutrophils differs from secretion of VEGF and other proteins in ␤-granules, because Ang1 is cytosolic instead of in granules and its release is neither calcium dependent nor evoked by TNF-␣ or other neutrophil-activating cytokines. 45 Vascular remodeling after infection was associated with increased Ang2 expression and decreased Tie2 phosphorylation, which are consistent with Ang2-mediated inactivation of Tie2 signaling as a trigger for the vascular remodeling. If, when, where, and how much Ang1 is released and the contribution of neutrophil Ang1 to the response remain to be determined.…”

Section: Discussionsupporting

confidence: 60%

“…28 Similarly, purified circulating human neutrophils contain Ang1-but not Ang2. 45 The earlier study found an increase in Ang1 protein assessed in Western blots, 28 and the present study found a decrease in Ang1 mRNA expression measured by qRT-PCR. Ang1 is likely to be stored in neutrophils as previously synthesized protein and not accompanied by a corresponding level of expression of Ang1 mRNA.…”

Section: Discussionmentioning

confidence: 63%

“…Ang1 and VEGF in circulating human neutrophils are released in equal amounts by phorbol myristate acetate stimulation, but expression of Ang1 mRNA is 92% lower than expression of VEGF mRNA. 45 Neutrophil ␤-granule-associated proteins elastase and myeloperoxidase are synthesized during differentiation and stored until secretion at sites of inflammation. 46,47 Ang1 mRNA expression may be similarly down-regulated during the final steps of neutrophil maturation.…”

Section: Discussionmentioning

confidence: 99%

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Angiopoietin-2-Driven Vascular Remodeling in Airway Inflammation

Tabruyn

Colton

Morisada

et al. 2010

The American Journal of Pathology

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Vascular remodeling is a feature of chronic inflammation during which capillaries transform into venules that expand the region of the vasculature in which leakage and leukocyte emigration both occur. Recently, we found that angiopoietin/Tie2 receptor signaling drives the transformation of capillaries into venules at an early stage of the sustained inflammatory response in the airways of mice infected with Mycoplasma pulmonis. However, the precise contributions of both angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) are not clear. In this study, we sought to determine the contribution of Ang2 to this vascular remodeling. Ang2 mRNA expression levels increased and phosphorylated Tie2 immunoreactivity in mucosal blood vessels decreased, indicative of diminished receptor signaling after infection. Selective inhibition of Ang2 throughout the infection by administration of either of two distinct functionblocking antibodies reduced the suppression of Tie2 phosphorylation and decreased the remodeling of mucosal capillaries into venules, the amount of leukocyte influx, and disease severity. These findings are consistent with Ang2 acting as an antagonist of Tie2 receptors and the reduction of Tie2 phosphorylation in endothelial cells rendering the vasculature more responsive to cytokines that promote both vascular remodeling and the consequences of inflammation after M. pulmonis infection. By blocking such changes, Ang2 inhibitors may prove beneficial in the treatment of sustained inflammation in which vascular remodeling, leakage, and leukocyte influx contribute to its pathophysiology.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

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Angiopoietin-2-Driven Vascular Remodeling in Airway Inflammation

Tabruyn

Colton

Morisada

et al. 2010

The American Journal of Pathology

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“…Similarly, it was recently reported that Ang1, but not Ang2, is expressed in human neutrophils where it is stored in the cytosolic fraction and released by phorbol myristate acetate. 41 Blockade of neutrophil infiltration results in reduced vascular remodeling after M. pulmonis, 28 supporting a role for neutrophil Ang1. Others have also reported that leukocytes represent a source of Ang1 in pathological conditions of vascular remodeling.…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin/Tie2 Signaling Transforms Capillaries into Venules Primed for Leukocyte Trafficking in Airway Inflammation

Fuxe

Lashnits

O’Brien

et al. 2010

The American Journal of Pathology

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Vascular endothelial growth factor (VEGF) is a key angiogenic factor in tumors, but less is known about what drives vascular remodeling in inflammation,where plasma leakage and leukocyte influx are prominent features. In chronic airway inflammation in mice infected by the bacterium Mycoplasma pulmonis (M. pulmonis), the segment of the microvasculature that supports leukocyte adhesion and migration expands through remodeling of capillaries into vessels with features of venules. Here, we report that the angiopoietin/Tie2 pathway is an essential driving force for capillary remodeling into venules in M. pulmonisinfected mouse airways. Similar to M. pulmonis infection, systemic overexpression of angiopoietin-1 (Ang1) resulted in remodeling of airway capillaries into venular-like vessels that expressed venous markers like Pselectin, ICAM-1, and EphB4 and were sites of leukocyte adhesion during lipopolysaccharide-induced acute inflammation. Ang1 and Ang2 protein increased in M. pulmonis-infected mouse airways but came from different cellular sources: Ang1 was expressed in infiltrating neutrophils and Ang2 in endothelial cells. Indeed, systemic administration of soluble Tie2 inhibited capillary remodeling, induction of venous markers, and leukocyte influx in M. pulmonis-infected mouse airways. Together, these findings suggest that blockade of the Ang/ Tie2 pathway may represent a therapeutic approach in airway inflammation.

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“…There are several possible explanations as follows: neutrophils can be stimulated to express various cytokines, which results in modifications to the microenvironment supportive of tumor progression and development [30]. Neagoe et al [31]. confirmed that tumor growth and metastasis can be promoted by neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil and platelet-to-lymphocyte ratio predicts outcomes in patients with unresectable hepatocellular carcinoma undergoing 131I-labeled-metuximab plus transarterial chemoembolization

Liu¹,

Zeng²,

Jia³

et al. 2018

Oncotarget

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Background: The prognostic value of NLR and PLR in unresectable HCC patients undergoing 131 I-labeled-metuximab plus transarterial chemoembolization has not been studied. Materials and Methods: 184 patients with unresectable HCC were enrolled from 2009 to 2011. Data were acquired through patients' medical records and follow-up. Receiver operating curves (ROC) were used to determine the optimal cutoff levels of NLR and PLR. Kaplan-Meier univariate analysis and multivariate Cox regression analysis were used to evaluate the correlation of the NLR, PLR, and other potential prognostic factors with overall survival. Results: The optimal cutoff levels were 2.5 for NLR and 105 for PLR by ROC curve analysis. Patients with NLR ≥ 2.5 and PLR ≥ 105 groups had significantly worse OS. The median survival time for patients with low NLR and high NLR were 19 months (2-35 months) and 10 months (2-34 months) respectively. And median survival time were 13 months (2-35 months) and 21 months (2-35 months) in the high and low PLR group respectively. Multivariate analysis showed that NLR ≥ 2.

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Expression and release of angiopoietin-1 from human neutrophils: Intracellular mechanisms

Cited by 18 publications

References 0 publications

Angiopoietin-2-Driven Vascular Remodeling in Airway Inflammation

Angiopoietin-2-Driven Vascular Remodeling in Airway Inflammation

Angiopoietin/Tie2 Signaling Transforms Capillaries into Venules Primed for Leukocyte Trafficking in Airway Inflammation

Neutrophil and platelet-to-lymphocyte ratio predicts outcomes in patients with unresectable hepatocellular carcinoma undergoing 131I-labeled-metuximab plus transarterial chemoembolization

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