ArticlePloS one2013
Deficiencies of the lipid-signaling enzymes phospholipase D1 and D2 alter cytoskeletal organization, macrophage phagocytosis, and cytokine-stimulated neutrophil recruitment.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 70 citations in OpenAlex.
- Phospholipase D: emerging therapeutic targets in signaling, metabolism, and immune-oncology.Cell communication and signaling : CCS · 2025Review
- Development and Evaluation of Indole-Based Phospholipase D Inhibitors for Lung Cancer Immunotherapy.Journal of medicinal chemistry · 2025Article
- Phospholipase D1 is a critical mediator of neutrophil extracellular trap formation and venous thrombosis.Frontiers in immunology · 2025Article
- PLD1 promotes spindle assembly and migration through regulating autophagy in mouse oocyte meiosis.Autophagy · 2024Article
- Inhibition of phospholipase D promotes neurological function recovery and reduces neuroinflammation after spinal cord injury in mice.Frontiers in cellular neuroscience · 2024Article
- Phospholipase D2 targeted by miR-5132-5p alleviates cerulein-induced acute pancreatitis via the Nrf2/NFκB pathway.Immunity, inflammation and disease · 2023Article
- Targeting Phospholipase D Pharmacologically Prevents Phagocytic Function Loss of Retinal Pigment Epithelium Cells Exposed to High Glucose Levels.International journal of molecular sciences · 2022Article
- Inhibition of phospholipase D1 induces immunogenic cell death and potentiates cancer immunotherapy in colorectal cancer.Experimental & molecular medicine · 2022Article
- Defining the proximal interaction networks of Arf GTPases reveals a mechanism for the regulation of PLD1 and PI4KB.The EMBO journal · 2022Article
- PLD1 and PLD2 differentially regulate the balance of macrophage polarization in inflammation and tissue injury.Journal of cellular physiology · 2021Article
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Mutations ofPlants (Basel, Switzerland) · 2020Article
- Genetic and Molecular Biology of Multiple Sclerosis Among Iranian Patients: An Overview.Cellular and molecular neurobiology · 2020Review
- Role of phospholipase D in bleomycin-induced mitochondrial reactive oxygen species generation, mitochondrial DNA damage, and pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- PLD-dependent phosphatidic acid microdomains are signaling platforms for podosome formation.Scientific reports · 2019Article
- Phospholipase D1 regulation of TNF-alpha protects against responses to LPS.Scientific reports · 2018Article
- Oxidized LDL phagocytosis during foam cell formation in atherosclerotic plaques relies on a PLD2-CD36 functional interdependence.Journal of leukocyte biology · 2018Article
- Phospholipase D isoforms differentially regulate leukocyte responses to acute lung injury.Journal of leukocyte biology · 2018Article
- Physiological function of phospholipase D2 in anti-tumor immunity: regulation of CD8Scientific reports · 2018Article
- Proliferative and metastatic roles for Phospholipase D in mouse models of cancer.Advances in biological regulation · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Cell migration and phagocytosis ensue from extracellular-initiated signaling cascades that orchestrate dynamic reorganization of the actin cytoskeleton. The reorganization is mediated by effector proteins recruited to the site of activity by locally-generated lipid second messengers. Phosphatidic acid (PA), a membrane phospholipid generated by multiple enzyme families including Phospholipase D (PLD), has been proposed to function in this role. Here, we show that macrophages prepared from mice lacking either of the classical PLD isoforms PLD1 or PLD2, or wild-type macrophages whose PLD activity has been pharmacologically inhibited, display isoform-specific actin cytoskeleton abnormalities that likely underlie decreases observed in phagocytic capacity. Unexpectedly, PA continued to be detected on the phagosome in the absence of either isoform and even when all PLD activity was eliminated. However, a disorganized phagocytic cup was observed as visualized by imaging PA, F-actin, Rac1, an organizer of the F-actin network, and DOCK2, a Rac1 activator, suggesting that PLD-mediated PA production during phagocytosis is specifically critical for the integrity of the process. The abnormal F-actin reorganization additionally impacted neutrophil migration and extravasation from the vasculature into interstitial tissues. Although both PLD1 and PLD2 were important in these processes, we also observed isoform-specific functions. PLD1-driven processes in particular were observed to be critical in transmigration of macrophages exiting the vasculature during immune responses such as those seen in acute pancreatitis or irritant-induced skin vascularization.
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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.