ArticleProceedings of the National Academy of Sciences of the United States of America2004
Leukocyte adhesion during hypoxia is mediated by HIF-1-dependent induction of beta2 integrin gene expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
What it found
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The trial behind it
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Who cites it
101 citing papers in PubMed, 243 citations in OpenAlex.
- Decoding signaling crosstalk in pulpitis: pathogenesis and precision therapeutics.Frontiers in cell and developmental biology · 2026Review
- Hypoxia-induced regulations of cell adhesion molecules and their implications for pathogenesis, diagnosis, and treatment of endometriosis.Frontiers in molecular biosciences · 2026Review
- Hypoxia and Multilineage Communication in 3D Organoids for Human Disease Modeling.Biomimetics (Basel, Switzerland) · 2025Review
- Oxygen-Mediated Molecular Mechanisms Involved in Intestinal Ischemia and Reperfusion Injury.International journal of molecular sciences · 2025Review
- Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury.Clinical and translational medicine · 2025Review
- Preoperative fasting glucose value can predict acute kidney injury in non-cardiac surgical patients without diabetes but not in patients with diabetes.Perioperative medicine (London, England) · 2024Article
- Article
- Anemia and Hypoxia Impact on Chronic Kidney Disease Onset and Progression: Review and Updates.Cureus · 2023Review
- Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers.International journal of molecular sciences · 2023Review
- Long Noncoding RNA AC078850.1 Induces NLRP3 Inflammasome-Mediated Pyroptosis in Atherosclerosis by Upregulating ITGB2 Transcription via Transcription Factor HIF-1α.Biomedicines · 2023Article
- Decreased expression of hypoxia-inducible factor 1α (HIF-1α) in cord blood monocytes under anoxia.Pediatric research · 2023Article
- A microfluidic device for assessment of E-selectin-mediated neutrophil recruitment to inflamed endothelium and prediction of therapeutic response in sickle cell disease.Biosensors & bioelectronics · 2023Article
- The resurgence of the Adora2b receptor as an immunotherapeutic target in pancreatic cancer.Frontiers in immunology · 2023Review
- Cigarette smoke-induced airspace disease in mice develops independently of HIF-1α signaling in leukocytes.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Article
- Hypoxia-inducible factors: cancer progression and clinical translation.The Journal of clinical investigation · 2022Review
- Hypoxia-Inducible Factors and Burn-Associated Acute Kidney Injury-A New Paradigm?International journal of molecular sciences · 2022Review
- Clinical Potential of Hypoxia Inducible Factors Prolyl Hydroxylase Inhibitors in Treating Nonanemic Diseases.Frontiers in pharmacology · 2022Review
- Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies.Frontiers in oncology · 2022Review
- Activated neutrophils in the initiation and progression of COVID-19: hyperinflammation and immunothrombosis in COVID-19.American journal of translational research · 2022Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Inflammatory responses are associated with significant changes in tissue metabolism. In particular, metabolic shifts during inflammation can result in significant tissue hypoxia, with resultant induction of hypoxia-responsive genes. Given this association, we hypothesized that leukocyte functional responses are influenced by hypoxia. Initial experiments revealed that exposure of the promonocytic cell line U937 to hypoxia resulted in increased adhesion to activated endothelia. Such increases were transcription-dependent and were blocked by antibodies directed against beta2, but not beta1, integrins. Analysis of beta2 integrin mRNA and protein in U937 cells revealed a 5- to 6-fold increase with hypoxia. Extension of this analysis to hypoxic human whole blood revealed prominent induction of beta2 integrin mRNA and protein ex vivo. Furthermore, murine beta2 integrin mRNA was found to be significantly induced during hypoxia in vivo. Subsequent studies identified a binding site for hypoxia-inducible factor 1 (HIF-1) in the CD18 gene. This gene encodes the subunit common to all four known types of beta2 integrin heterodimer. HIF-1 binding was demonstrated in vivo, and mutational analysis of the HIF-1 site within the CD18 promoter resulted in a loss of hypoxia inducibility. Taken together, these results demonstrate that hypoxia induces leukocyte beta2 integrin expression and function by transcriptional mechanisms dependent upon HIF-1.
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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.