ArticleAmerican journal of physiology. Lung cellular and molecular physiology2009
Neutrophil elastase cleaves VEGF to generate a VEGF fragment with altered activity.
Article in American journal of physiology. Lung cellular and molecular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Neutrophils in non-small cell lung cancer and immunotherapy with PD-1/PD-L1 inhibitors.Journal of translational medicine · 2025Review
- VEGF-A, -C, -D, VEGFR1, -2, -3, PDGF-BB and FGF-2 join forces to induce vascular and lymphatic angiogenesis during bone healing of hip implants.Bone reports · 2025Article
- Role of alpha-1 antitrypsin in Bruch's membrane integrity.Scientific reports · 2025Article
- Article
- PR1P, a VEGF-stabilizing peptide, reduces injury and inflammation in acute lung injury and ulcerative colitis animal models.Frontiers in immunology · 2023Article
- The Prominin-1-Derived Peptide Improves Cardiac Function Following Ischemia.International journal of molecular sciences · 2021Article
- Neutrophil-derived granule cargoes: paving the way for tumor growth and progression.Cancer metastasis reviews · 2021Review
- Systemic Immune-Inflammation Index Is a Prognostic Factor for Breast Cancer Patients After Curative Resection.Frontiers in oncology · 2021Article
- Neutrophil Elastase Facilitates Tumor Cell Intravasation and Early Metastatic Events.iScience · 2020Article
- PR1P Stabilizes VEGF and Upregulates Its Signaling to Reduce Elastase-induced Murine Emphysema.American journal of respiratory cell and molecular biology · 2020Article
- Hypoxia Induced Heparan Sulfate Primes the Extracellular Matrix for Endothelial Cell Recruitment by Facilitating VEGF-Fibronectin Interactions.International journal of molecular sciences · 2019Article
- Enhanced Survival and Accelerated Perfusion of Skin Flap to Recipient Site Following Administration of Human α1-Antitrypsin in Murine Models.Advances in wound care · 2019Article
- Impact of one versus two doses of mesenchymal stromal cells on lung and cardiovascular repair in experimental emphysema.Stem cell research & therapy · 2018Article
- Neutrophil Elastase Subverts the Immune Response by Cleaving Toll-Like Receptors and Cytokines in Pneumococcal Pneumonia.Frontiers in immunology · 2018Article
- Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model.Cell stress & chaperones · 2015Article
- Article
- Granzyme B releases vascular endothelial growth factor from extracellular matrix and induces vascular permeability.Laboratory investigation; a journal of technical methods and pathology · 2014Article
- Extracellular regulation of VEGF: isoforms, proteolysis, and vascular patterning.Cytokine & growth factor reviews · 2014Review
- Promoting effect of neutrophils on lung tumorigenesis is mediated by CXCR2 and neutrophil elastase.Molecular cancer · 2013Article
- Expanding the clinical indications for α(1)-antitrypsin therapy.Molecular medicine (Cambridge, Mass.) · 2012Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Excessive neutrophil elastase (NE) activity and altered vascular endothelial growth factor (VEGF) signaling have independently been implicated in the development and progression of pulmonary emphysema. In the present study, we investigated the potential link between NE and VEGF. We noted that VEGF(165) is a substrate for NE. Digestion of purified VEGF(165) with NE generated a partially degraded disulfide-linked fragment of VEGF. Mass spectrometric analysis revealed that NE likely cleaves VEGF(165) at both the NH(2) and COOH termini to produce VEGF fragment chains approximately 5 kDa reduced in size. NE treatment of VEGF-laden endothelial cell cultures and smooth muscle cells endogenously expressing VEGF generated VEGF fragments similar to those observed with purified VEGF(165). NE-generated VEGF fragment showed significantly reduced binding to VEGF receptor 2 and heparin yet retained the ability to bind to VEGF receptor 1. Interestingly, VEGF fragment showed altered signaling in pulmonary artery endothelial cells compared with intact VEGF(165). Specifically, treatment with VEGF fragment did not activate extracellular-regulated kinases 1 and 2 (ERK1/2), yet resulted in enhanced activation of protein kinase B (Akt). Treatment of monocyte/macrophage RAW 264.7 cells with VEGF fragment, on the other hand, led to both Akt and ERK1/2 activation, increased VEGFR1 expression, and stimulated chemotaxis. These findings suggest that the tissue response to NE-mediated injury might involve the generation of diffusible VEGF fragments that stimulate inflammatory cell recruitment and activation via VEGF receptor 1.
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Registered trials
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