ArticleBlood2016
Gnb isoforms control a signaling pathway comprising Rac1, Plcβ2, and Plcβ3 leading to LFA-1 activation and neutrophil arrest in vivo.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Alveolar epithelial and vascular CXCR2 mediates transcytosis of CXCL1 in inflamed lungs.Nature communications · 2025Article
- Interaction Between Neutrophils and Elements of the Blood-Brain Barrier in the Context of Multiple Sclerosis and Ischemic Stroke.International journal of molecular sciences · 2025Review
- RNAi library screening reveals Gβ1, Casein Kinase 2 and ICAP-1 as novel regulators of LFA-1-mediated T cell polarity and migration.Immunology and cell biology · 2025Article
- A multidimensional recommendation framework for identifying biological targets to aid the diagnosis and treatment of liver metastasis in patients with colorectal cancer.Molecular cancer · 2024Article
- IL-13 and IL-17A activate β1 integrin through an NF-kB/Rho kinase/PIP5K1γ pathway to enhance force transmission in airway smooth muscle.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- IL-13 and IL-17A Activate β1 Integrin through an NF-kB/Rho kinase/PIP5K1γ pathway to Enhance Force Transmission in Airway Smooth Muscle.bioRxiv : the preprint server for biology · 2024Article
- Nexinhib20 Inhibits Neutrophil Adhesion and βJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Genome-scale CRISPR screening reveals that C3aR signaling is critical for rapid capture of fungi by macrophages.PLoS pathogens · 2022Article
- Review
- Mitofusin-2 regulates leukocyte adhesion and β2 integrin activation.Journal of leukocyte biology · 2022Article
- Immune microenvironment-related gene mapping predicts immunochemotherapy response and prognosis in diffuse large B-cell lymphoma.Medical oncology (Northwood, London, England) · 2022Article
- β2 integrin activation and signal transduction in leukocyte recruitment.American journal of physiology. Cell physiology · 2021Review
- Full spectrum of clonal haematopoiesis-driver mutations in chronic heart failure and their associations with mortality.ESC heart failure · 2021Article
- Natural Killer Cell Integrins and Their Functions in Tissue Residency.Frontiers in immunology · 2021Review
- TAS2R16 Activation Suppresses LPS-Induced Cytokine Expression in Human Gingival Fibroblasts.Frontiers in immunology · 2021Article
- Intravascular adhesion and recruitment of neutrophils in response to CXCL1 depends on their TRPC6 channels.Journal of molecular medicine (Berlin, Germany) · 2020Article
- β2 Integrins-Multi-Functional Leukocyte Receptors in Health and Disease.International journal of molecular sciences · 2020Review
- Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α.eLife · 2019Article
- DDX3 Participates in Translational Control of Inflammation Induced by Infections and Injuries.Molecular and cellular biology · 2019Article
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10 authors at 4 institutions in 2 countries.
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Abstract
Chemokines are required for leukocyte recruitment and appropriate host defense and act through G protein-coupled receptors (GPCRs), which induce downstream signaling leading to integrin activation. Although the α and β subunits of the GPCRs are the first intracellular molecules that transduce signals after ligand binding and are therefore indispensable for downstream signaling, relatively little is known about their contribution to lymphocyte function-associated antigen 1 (LFA-1) activation and leukocyte recruitment. We used knockout mice and short hairpin RNA to knock down guanine nucleotide binding protein (GNB) isoforms (GNB1, GNB2, GNB4, and GNB5) in HL60 cells and primary murine hematopoietic cells. Neutrophil function was assessed by using intravital microscopy, flow chamber assays, and chemotaxis and biochemistry studies. We unexpectedly discovered that all expressed GNB isoforms are required for LFA-1 activation. Their downregulation led to a significant impairment of LFA-1 activation, which was demonstrated in vitro and in vivo. Furthermore, we showed that GPCR activation leads to Ras-related C3 botulinum toxin substrate 1 (Rac1)-dependent activation of both phospholipase C β2 (Plcβ2) and Plcβ3. They act nonredundantly to produce inositol triphosphate-mediated intracellular Ca(2+) flux and LFA-1 activation that support chemokine-induced arrest in vivo. In a complex inflammatory disease model, Plcβ2-, Plcβ3-, or Rac1-deficient mice were protected from lipopolysaccharide-induced lung injury. Taken together, we demonstrated that all Gnb isoforms are required for chemokine-induced downstream signaling, and Rac1, Plcβ2, and Plcβ3 are critically involved in integrin activation and leukocyte arrest.
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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.