Evidence map›Paper›PMID 20709956›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2010

Activation of macrophages by P2X7-induced microvesicles from myeloid cells is mediated by phospholipids and is partially dependent on TLR4.

L Michael Thomas, Russell D Salter

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

55 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
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  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. P2XInternational journal of molecular sciences · 2023
    Review
  14. Extracellular Vesicles as Biomarkers in Liver Disease.International journal of molecular sciences · 2022
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Targeting CD39 in cancer.Nature reviews. Immunology · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

L Michael ThomasDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Russell D Salter
University of Pittsburgh · US

Funding

MECHANISMS OF DENDRITIC CELL BASED TUMOR IMMUNIZATIONP01CA073743 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FINN, OLIVERA J · 1998 to 2009
$12.3M
Training in Cellular & Molecular Mechanisms of Tumor RejectionT32CA082084 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Robert J Binder, Dario AA Vignali · 1999 to 2026
$9.2M
Interaction of microvesicles and bacterial toxins with immune cellsR01AI072083 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SALTER, RUSSELL D. · 2007 to 2011
$1.8M
NCI NIH HHS P01 CA073743NCI NIH HHS P01CA073743NCI NIH HHS T32 CA082084NCI NIH HHS T32CA082084NIAID NIH HHS R01 AI072083NIAID NIH HHS R01AI072083
6 · The paper itself

Abstract

ATP-mediated activation of the purinergic receptor P2X(7) elicits morphological changes and proinflammatory responses in macrophages. These changes include rapid shedding of microvesicles (MV) and the nonconventional secretion of cytokines, such as IL-1beta and IL-18 following priming. In this study, we demonstrate the activation potential of P2X(7)-induced MV isolated from nonprimed murine macrophages. Cotreatment of nonprimed macrophages with ATP and calcium ionophore induced a rapid release of MV that were predominantly 0.5-1 microm in size. Exposure of primary murine bone marrow-derived macrophages to these MV resulted in costimulatory receptor upregulation and TNF-alpha secretion. Cell homogenates or supernatants cleared of MV did not activate macrophages. MV-mediated activation was p38 MAPK and NF-kappaB dependent, and partially dependent on TLR4 activity, but was high-mobility group box 1 independent. Biochemical fractionation of the MV demonstrated that the phospholipid fraction, not the protein fraction, mediated macrophage activation through a TLR4-dependent process. P2X(7) activation is known to induce calcium-independent phospholipase A(2), calcium-dependent phospholipase A(2), and phospholipase D activities, but inhibition of these enzymes did not inhibit MV generation or shedding. However, blocking phospholipase D activity resulted in release of MV incapable of activating recipient macrophages. These data demonstrate a novel mechanism of macrophage activation resulting from exposure to MV from nonprimed macrophages, and identifies phospholipids in these MV as the biologically active component. We suggest that phospholipids delivered by MV may be mediators of sterile inflammation in a number of diseases.

Indexed as

AnimalsBone Marrow CellsCell LineHMGB1 ProteinHumansMacrophage ActivationMacrophagesMiceMice, Inbred C57BLMice, KnockoutMyeloid CellsNF-kappa Bp38 Mitogen-Activated Protein KinasesPhospholipidsReceptors, Purinergic P2X7Secretory VesiclesHMGB1 ProteinNF-kappa Bp38 Mitogen-Activated Protein KinasesPhospholipidsReceptors, Purinergic P2X7Tlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID20709956
PMCPMC2933301
OpenAlexW1824478393

What OpenQuestion holds

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Read underepoch 390

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.