ArticleThe Journal of experimental medicine2002
Discrete role for cytosolic phospholipase A(2)alpha in platelets: studies using single and double mutant mice of cytosolic and group IIA secretory phospholipase A(2).
Article in The Journal of experimental medicine, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 61 citations in OpenAlex.
- Inherited human group IVA cytosolic phospholipase A2 deficiency abolishes platelet, endothelial, and leucocyte eicosanoid generation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Trial
- NADPH oxidase 2 inhibitor GSK2795039 exerts antiplatelet and antithrombotic activity.Scientific reports · 2025Article
- Cytosolic phospholipase A2 in infiltrating monocyte derived macrophages does not impair recovery after spinal cord injury in female mice.Scientific reports · 2025Article
- Cytosolic Phospholipase A2 in Infiltrating Monocyte-Derived Macrophages Does Not Impair Recovery After Spinal Cord Injury in Female Mice.Research square · 2024Article
- Modulation of Glycoprotein VI and Its Downstream Signaling Pathways as an Antiplatelet Target.International journal of molecular sciences · 2022Review
- Apoptosis signal-regulating kinase 1 regulates immune-mediated thrombocytopenia, thrombosis, and systemic shock.Journal of thrombosis and haemostasis : JTH · 2020Article
- Structural and Functional Aspects of Targeting the Secreted Human Group IIA Phospholipase AMolecules (Basel, Switzerland) · 2020Review
- Platelets trigger perivascular mast cell degranulation to cause inflammatory responses and tissue injury.Science advances · 2020Article
- Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting.Journal of hematology & oncology · 2019Review
- Article
- Phospholipid signaling in innate immune cells.The Journal of clinical investigation · 2018Review
- Lipoquality control by phospholipase AProceedings of the Japan Academy. Series B, Physical and biological sciences · 2017Review
- Platelet Lipidomic Profiling: Novel Insight into Cytosolic Phospholipase A2α Activity and Its Role in Human Platelet Activation.Biochemistry · 2015Article
- Cytosolic phospholipase A₂: physiological function and role in disease.Journal of lipid research · 2015Review
- Group VIB calcium-independent phospholipase A2 (iPLA2γ) regulates platelet activation, hemostasis and thrombosis in mice.PloS one · 2014Article
- Protein kinase C isoform ε negatively regulates ADP-induced calcium mobilization and thromboxane generation in platelets.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
- Lipid signaling in cytosolic phospholipase A2alpha-cyclooxygenase-2 cascade mediates cerebellar long-term depression and motor learning.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Article
- The enteropathy of prostaglandin deficiency.Journal of gastroenterology · 2009Article
- Inherited human cPLA(2alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction.The Journal of clinical investigation · 2008Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among several different types of phospholipase A(2) (PLA(2)), cytosolic PLA(2) (cPLA(2))alpha and group IIA (IIA) secretory PLA(2) (sPLA(2)) have been studied intensively. To determine the discrete roles of cPLA(2)alpha in platelets, we generated two sets of genetically engineered mice (cPLA(2)alpha(-/-)/sPLA(2)-IIA(-/-) and cPLA(2)alpha(-/-)/sPLA(2)-IIA(+/+)) and compared their platelet function with their respective wild-type C57BL/6J mice (cPLA(2)alpha(+/+)/sPLA(2)-IIA(-/-)) and C3H/HeN (cPLA(2)alpha(+/+)/sPLA(2)-IIA(+/+)). We found that cPLA(2)alpha is needed for the production of the vast majority of thromboxane (TX)A(2) with collagen stimulation of platelets. In cPLA(2)alpha-deficient mice, however, platelet aggregation in vitro is only fractionally decreased because small amounts of TX produced by redundant phospholipase enzymes sufficiently preserve aggregation. In comparison, adenosine triphosphate activation of platelets appears wholly independent of cPLA(2)alpha and sPLA(2)-IIA for aggregation or the production of TX, indicating that these phospholipases are specifically linked to collagen receptors. However, the lack of high levels of TX limiting vasoconstriction explains the in vivo effects seen: increased bleeding times and protection from thromboembolism. Thus, cPLA(2)alpha plays a discrete role in the collagen-stimulated production of TX and its inhibition has a therapeutic potential against thromboembolism, with potentially limited bleeding expected.
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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.