ArticleBlood2015
Identification and characterization of VEGF-A-responsive neutrophils expressing CD49d, VEGFR1, and CXCR4 in mice and humans.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 235 citations in OpenAlex.
- Cardiac repair after myocardial infarction: A two-sided role of inflammation-mediated.Frontiers in cardiovascular medicine · 2022Pooled it
- Absolute numbers of regulatory T cells and neutrophils in corticosteroid-free patients are predictive for response to bevacizumab in recurrent glioblastoma patients.Cancer immunology, immunotherapy : CII · 2019Trial
- A skin-kidney neutrophil axis links ultraviolet exposure to renal angiogenesis and tissue remodeling in healthy and lupus kidneys.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Dose-Dependent Alterations in Lung Immune Subpopulations in Influenza a Virus Infection.International journal of molecular sciences · 2026Article
- VEGFR Blockade ReducesCells · 2026Article
- Neutrophil heterogeneity in Kawasaki disease and multisystem inflammatory syndrome in children.Pediatric research · 2026Review
- Neutrophil-initiated nociceptive ingrowth orchestrates inflammation resolution to potentiate bone regeneration.Bone research · 2026Article
- Immuno-metabolic dysregulation in type 2 diabetes is associated with altered neutrophil functional plasticity, mitochondrial dysfunction, and compromised responses in sepsis.Journal of translational medicine · 2026Article
- Multimodal single-cell protein and RNA profiling unveils dysregulated immature neutrophil dynamics in gestational diabetes mellitus.Communications biology · 2026Article
- ExploitingFrontiers in immunology · 2026Article
- Lysyl Oxidase Promotes Actin-Dependent Neutrophil Activation and Cytotoxicity Toward Retinal Endothelial Cells in Diabetes.Diabetes · 2026Article
- Sex-dependent transcriptional and epigenetic regulation of neutrophil inflammatory programs in COPD.Frontiers in immunology · 2026Article
- Differential Neutrophil Responses to Smooth Titanium: A Double-Edged Sword for the Abutment-Gingival Interface (An In Vitro Study).International journal of dentistry · 2026Article
- Directing Neutrophil Fate via Sensory-Immune Interactions Accelerates Diabetic Bone Healing.Research (Washington, D.C.) · 2026Article
- The neutrophil collective.Cell · 2025Review
- VEGFR1 as a Target for Cardiovascular Gene Therapy.Journal of cardiovascular translational research · 2025Review
- Engineered immune-driven theranostics for clinical cardiology.Military Medical Research · 2025Review
- Hypoxic-ischemic brain injury in neonatal mice sequentially recruits neutrophils with dichotomous phenotype and function.Nature communications · 2025Article
- Beyond Killing: The Overlooked Contribution of Neutrophils to Tissue Repair.International journal of molecular sciences · 2025Review
- Integrating Machine Learning and Multi-Omics to Explore Neutrophil Heterogeneity.Biomedicines · 2025Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factor A (VEGF-A) is upregulated during hypoxia and is the major regulator of angiogenesis. VEGF-A expression has also been found to recruit myeloid cells to ischemic tissues where they contribute to angiogenesis. This study investigates the mechanisms underlying neutrophil recruitment to VEGF-A as well as the characteristics of these neutrophils. A previously undefined circulating subset of neutrophils shown to be CD49d(+)VEGFR1(high)CXCR4(high) was identified in mice and humans. By using chimeric mice with impaired VEGF receptor 1 (VEGFR1) or VEGFR2 signaling (Flt-1tk(-/-), tsad(-/-)), we found that parallel activation of VEGFR1 on neutrophils and VEGFR2 on endothelial cells was required for VEGF-A-induced recruitment of circulating neutrophils to tissue. Intravital microscopy of mouse microcirculation revealed that neutrophil recruitment by VEGF-A versus by the chemokine macrophage inflammatory protein 2 (MIP-2 [CXCL2]) involved the same steps of the recruitment cascade but that an additional neutrophil integrin (eg, VLA-4 [CD49d/CD29]) played a crucial role in neutrophil crawling and emigration to VEGF-A. Isolated CD49d(+) neutrophils featured increased chemokinesis but not chemotaxis compared with CD49d(-) neutrophils in the presence of VEGF-A. Finally, by targeting the integrin α4 subunit (CD49d) in a transplantation-based angiogenesis model that used avascular pancreatic islets transplanted to striated muscle, we demonstrated that inhibiting the recruitment of circulating proangiogenic neutrophils to hypoxic tissue impairs vessel neoformation. Thus, angiogenesis can be modulated by targeting cell-surface receptors specifically involved in VEGF-A-dependent recruitment of proangiogenic neutrophils without compromising recruitment of the neutrophil population involved in the immune response to pathogens.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.