Evidence map›Paper›PMID 24335501›Full record

ArticleBlood2014

Polyphosphate suppresses complement via the terminal pathway.

Jovian M Wat, Jonathan H Foley, Michael J Krisinger, Linnette Mae Ocariza, Victor Lei, Gregory A Wasney, Emilie Lameignere, Natalie C Strynadka, Stephanie A Smith, James H Morrissey and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

32 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Platelets and Complement Cross-Talk in Early Atherogenesis.Frontiers in cardiovascular medicine · 2019
    Review
  19. Review
  20. Polyphosphate in thrombosis, hemostasis, and inflammation.Research and practice in thrombosis and haemostasis · 2019
    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

11 authors at 2 institutions in 2 countries.

Jovian M WatCentre for Blood Research, Life Sciences Institute.
Jonathan H Foley
Michael J Krisinger
Linnette Mae Ocariza
Victor Lei
Gregory A Wasney
Emilie Lameignere
Natalie C Strynadka
Stephanie A Smith
James H Morrissey
Edward M Conway
University of British Columbia · CAUniversity of Illinois Urbana-Champaign · US

Funding

MECHANISMS OF TISSUE FACTOR/FACTOR VII ASSEMBLYR01HL047014 · NHLBI · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI MORRISSEY, JAMES H. · 1992 to 2016
$4.9M
CIHRHoward Hughes Medical InstituteNHLBI NIH HHS R01 HL047014NHLBI NIH HHS R01 HL47014
6 · The paper itself

Abstract

Polyphosphate, synthesized by all cells, is a linear polymer of inorganic phosphate. When released into the circulation, it exerts prothrombotic and proinflammatory activities by modulating steps in the coagulation cascade. We examined the role of polyphosphate in regulating the evolutionarily related proteolytic cascade complement. In erythrocyte lysis assays, polyphosphate comprising more than 1000 phosphate units suppressed total hemolytic activity with a concentration to reduce maximal lysis to 50% that was 10-fold lower than with monophosphate. In the ion- and enzyme-independent terminal pathway complement assay, polyphosphate suppressed complement in a concentration- and size-dependent manner. Phosphatase-treated polyphosphate lost its ability to suppress complement, confirming that polymer integrity is required. Sequential addition of polyphosphate to the terminal pathway assay showed that polyphosphate interferes with complement only when added before formation of the C5b-7 complex. Physicochemical analyses using native gels, gel filtration, and differential scanning fluorimetry revealed that polyphosphate binds to and destabilizes C5b,6, thereby reducing the capacity of the membrane attack complex to bind to and lyse the target cell. In summary, we have added another function to polyphosphate in blood, demonstrating that it dampens the innate immune response by suppressing complement. These findings further establish the complex relationship between coagulation and innate immunity.

Indexed as

Blood CoagulationComplement C5Complement System ProteinsErythrocytesHemolysisHumansPolyphosphatesComplement C5complement C5b-7 complexComplement System ProteinsPolyphosphates

Identifiers

PMID24335501
PMCPMC3907762
OpenAlexW2076684617

What OpenQuestion holds

Textmetadata
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.