ArticleThe Journal of biological chemistry2008
Signaling and cross-talk by C5a and UDP in macrophages selectively use PLCbeta3 to regulate intracellular free calcium.
Article in The Journal of biological chemistry, 2008. 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, 45 citations in OpenAlex.
- Inadequate cytoplasmatic calcium signals in alveolar macrophages after cardiac surgery.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2010Trial
- PLCβs are recruited to the plasma membrane in macrophages by both Gβγ and GαProceedings of the National Academy of Sciences of the United States of America · 2026Article
- PLCβs are recruited to the plasma membrane in macrophages by both Gβγ and GαbioRxiv : the preprint server for biology · 2026Article
- ACSL4 Drives C5a/C5aR1-Calcium-Induced Fibroblast-to-Myofibroblast Transition in a Bleomycin-Induced Mouse Model of Pulmonary Fibrosis.Biomolecules · 2025Article
- Article
- The mechanism ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Molecular regulation of PLCβ signaling.Methods in enzymology · 2023Review
- Vascular Endothelial Cells Produce Coagulation Factors That Control Their Growth via Joint Protease-Activated Receptor and C5a Receptor 1 (CD88) Signaling.The American journal of pathology · 2022Article
- RTK signaling requires C3ar1/C5ar1 and IL-6R joint signaling to repress dominant PTEN, SOCS1/3 and PHLPP restraint.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- PI3Kβ is selectively required for growth factor-stimulated macropinocytosis.Journal of cell science · 2019Article
- Macrophage centripetal migration drives spontaneous healing process after spinal cord injury.Science advances · 2019Article
- Gγ identity dictates efficacy of Gβγ signaling and macrophage migration.The Journal of biological chemistry · 2018Article
- The Role of Phospholipase C Signaling in Macrophage-Mediated Inflammatory Response.Journal of immunology research · 2018Review
- The Complement System Component C5a Produces Thermal Hyperalgesia via Macrophage-to-Nociceptor Signaling That Requires NGF and TRPV1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- The PRKAA1/AMPKα1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML.Autophagy · 2015Article
- Structural insights into phospholipase C-β function.Molecular pharmacology · 2013Review
- Circuit-level input integration in bacterial gene regulation.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Receptors responsive to protein breakdown products in g-cells and d-cells of mouse, swine and human.Frontiers in physiology · 2012Article
- Phospholipase C-β3 is a key modulator of IL-8 expression in cystic fibrosis bronchial epithelial cells.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Studies in fibroblasts, neurons, and platelets have demonstrated the integration of signals from different G protein-coupled receptors (GPCRs) in raising intracellular free Ca(2+). To study signal integration in macrophages, we screened RAW264.7 cells and bone marrow-derived macrophages (BMDM) for their Ca(2+) response to GPCR ligands. We found a synergistic response to complement component 5a (C5a) in combination with uridine 5'-diphosphate (UDP), platelet activating factor (PAF), or lysophosphatidic acid (LPA). The C5a response was Galpha(i)-dependent, whereas the UDP, PAF, and LPA responses were Galpha(q)-dependent. Synergy between C5a and UDP, mediated by the C5a and P2Y6 receptors, required dual receptor occupancy, and affected the initial release of Ca(2+) from intracellular stores as well as sustained Ca(2+) levels. C5a and UDP synergized in generating inositol 1,4,5-trisphosphate, suggesting synergy in activating phospholipase C (PLC) beta. Macrophages expressed transcripts for three PLCbeta isoforms (PLCbeta2, PLCbeta3, and PLCbeta4), but GPCR ligands selectively used these isoforms in Ca(2+) signaling. C5a predominantly used PLCbeta3, whereas UDP used PLCbeta3 but also PLCbeta4. Neither ligand required PLCbeta2. Synergy between C5a and UDP likewise depended primarily on PLCbeta3. Importantly, the Ca(2+) signaling deficiency observed in PLCbeta3-deficient BMDM was reversed by re-constitution with PLCbeta3. Neither phosphatidylinositol (PI) 3-kinase nor protein kinase C was required for synergy. In contrast to Ca(2+), PI 3-kinase activation by C5a was inhibited by UDP, as was macropinocytosis, which depends on PI 3-kinase. PLCbeta3 may thus provide a selective target for inhibiting Ca(2+) responses to mediators of inflammation, including C5a, UDP, PAF, and LPA.
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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.