Evidence map›Paper›PMID 26106157›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A2-IIA.

Anne-Claire Duchez, Luc H Boudreau, Gajendra S Naika, James Bollinger, Clémence Belleannée, Nathalie Cloutier, Benoit Laffont, Raifish E Mendoza-Villarroel, Tania Lévesque, Emmanuelle Rollet-Labelle and 10 more

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 134 papers.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed
11.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

134 citing papers in PubMed, 238 citations in OpenAlex.

  1. Review
  2. Article
  3. The Phospholipase AJournal of lipid and atherosclerosis · 2026
    Review
  4. sPLAScience advances · 2026
    Article
  5. Secreted phospholipase PLA2G5 acts as a hemolytic factor in sepsis.The Journal of clinical investigation · 2026
    Article
  6. Review
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  8. Therapeutic and diagnostic potential of extracellular vesicle (EV)-mediated intercellular transfer of mitochondria and mitochondrial components.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  9. Review
  10. From pathogenesis to therapy: extracellular vesicles in osteoarthritis.Frontiers in bioengineering and biotechnology · 2026
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Secretory phospholipase ACommunications biology · 2025
    Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article

74 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 3 countries.

Anne-Claire DuchezCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Luc H BoudreauCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Gajendra S Naika
James BollingerDepartment of Chemistry, University of Washington, Seattle, WA 98195;
Clémence BelleannéeCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département d'Obstétrique, Gynécologie et Reproduction, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Nathalie CloutierCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Benoit LaffontCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Raifish E Mendoza-VillarroelCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département d'Obstétrique, Gynécologie et Reproduction, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Tania LévesqueCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Emmanuelle Rollet-LabelleCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Matthieu RousseauCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Isabelle AllaeysCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Jacques J TremblayCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département d'Obstétrique, Gynécologie et Reproduction, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Patrice E PoubelleCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Gérard LambeauInstitut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Centre National de la Recherche Scientifique, Université de Nice Sophia Antipolis, 06250 Valbonne, France;
Marc PouliotCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Patrick ProvostCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada;
Denis SouletCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Psychiatrie et Neurosciences, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada.
Michael H GelbDepartment of Chemistry, University of Washington, Seattle, WA 98195;
Eric BoilardCentre de Recherche du Centre Hospitalier Universitaire de Québec, Département de Microbiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2 Canada; eric.boilard@crchudequebec.ulaval.ca.
Centre hospitalier universitaire de Québec · CAUniversité Laval · CAUniversity of Washington · USInstitut de Pharmacologie Moléculaire et Cellulaire · FR

Funding

Biochemical Studies of 14-kDa Phospholipases A2R37HL036235 · NHLBI · UNIVERSITY OF WASHINGTON · PI GELB, MICHAEL H · 2007 to 2016
$4.1M
Canadian Institutes of Health ResearchNHLBI NIH HHS R37 HL036235NHLBI NIH HHS R37 HL36235
6 · The paper itself

Abstract

Platelets are anucleated blood elements highly potent at generating extracellular vesicles (EVs) called microparticles (MPs). Whereas EVs are accepted as an important means of intercellular communication, the mechanisms underlying platelet MP internalization in recipient cells are poorly understood. Our lipidomic analyses identified 12(S)-hydroxyeicosatetranoic acid [12(S)-HETE] as the predominant eicosanoid generated by MPs. Mechanistically, 12(S)-HETE is produced through the concerted activity of secreted phospholipase A2 IIA (sPLA2-IIA), present in inflammatory fluids, and platelet-type 12-lipoxygenase (12-LO), expressed by platelet MPs. Platelet MPs convey an elaborate set of transcription factors and nucleic acids, and contain mitochondria. We observed that MPs and their cargo are internalized by activated neutrophils in the endomembrane system via 12(S)-HETE. Platelet MPs are found inside neutrophils isolated from the joints of arthritic patients, and are found in neutrophils only in the presence of sPLA2-IIA and 12-LO in an in vivo model of autoimmune inflammatory arthritis. Using a combination of genetically modified mice, we show that the coordinated action of sPLA2-IIA and 12-LO promotes inflammatory arthritis. These findings identify 12(S)-HETE as a trigger of platelet MP internalization by neutrophils, a mechanism highly relevant to inflammatory processes. Because sPLA2-IIA is induced during inflammation, and 12-LO expression is restricted mainly to platelets, these observations demonstrate that platelet MPs promote their internalization in recipient cells through highly regulated mechanisms.

Indexed as

12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAnimalsArachidonate 12-LipoxygenaseArthritis, ExperimentalArthritis, RheumatoidBlood PlateletsCell-Derived MicroparticlesCell LineCells, CulturedEndocytosisGroup II Phospholipases A2HumansImmunoblottingMice, Inbred C57BLMice, KnockoutMice, Transgenic12-Hydroxy-5,8,10,14-eicosatetraenoic AcidArachidonate 12-LipoxygenaseGroup II Phospholipases A2RNA12-lipoxygenasemicroparticlesneutrophilsphospholipase A2platelets

Identifiers

PMID26106157
PMCPMC4500271
OpenAlexW844791963

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

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.