Evidence map›Paper›PMID 25411427›Full record

ArticleBlood2015

Cell rigidity and shape override CD47's "self"-signaling in phagocytosis by hyperactivating myosin-II.

Nisha G Sosale, Tahereh Rouhiparkouhi, Andrew M Bradshaw, Rumiana Dimova, Reinhard Lipowsky, Dennis E Discher

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
2.9field-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

103 citing papers in PubMed, 154 citations in OpenAlex.

  1. Article
  2. Review
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  9. Article
  10. Humanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Perfluorocarbon-Loaded Poly(lactide-ACS applied polymer materials · 2025
    Article
  17. Article
  18. Review
  19. Article
  20. Biomechanics of phagocytosis of red blood cells by macrophages in the human spleen.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article

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

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

6 authors at 2 institutions in 2 countries.

Nisha G SosaleMolecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA; and.ORCID http://orcid.org/0000-0002-5903-5916
Tahereh RouhiparkouhiMax Planck Institute of Colloids and Interfaces, Potsdam, Germany.
Andrew M BradshawMolecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA; and.
Rumiana DimovaMax Planck Institute of Colloids and Interfaces, Potsdam, Germany.
Reinhard LipowskyMax Planck Institute of Colloids and Interfaces, Potsdam, Germany.
Dennis E DischerMolecular and Cell Biophysics Laboratory, University of Pennsylvania, Philadelphia, PA; and.
Max Planck Institute of Colloids and Interfaces · DEUniversity of Pennsylvania · US

Funding

Institutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9M
YEAST MEMBRANE CYTOSKELETONP01DK032094 · NIDDK · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI NARLA, MOHANDAS · 1987 to 2021
$26.7M
PSOC@Penn Education and OutreachU54CA193417 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2015 to 2020
$10.5M
Research BaseP30DK090969 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI CARROLL, MARTIN · 2010 to 2015
$5.7M
SPECTRIN EXTENSIBILITY and CD47 CONNECTIONS &FUNCTIONR01HL062352 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 1999 to 2012
$3.3M
Nanoscience of 'Self' - reductionist approaches to hCD47 inhibition of phagocytesR01HL124106 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2014 to 2022
$3.1M
Carrier Shape Matters: Filomicelles, Long-circulation, and the EPR effectR01EB007049 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2006 to 2014
$2.8M
CD47-Display on NanomaterialsR21EB003164 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2003 to 2004
$360k
NCATS NIH HHS 8UL1TR000003NCATS NIH HHS UL1 TR000003NCI NIH HHS U54 CA193417NHLBI NIH HHS R01 HL062352NHLBI NIH HHS R01 HL124106NHLBI NIH HHS R01-HL124106NIBIB NIH HHS R01 EB007049NIBIB NIH HHS R01-EB007049NIBIB NIH HHS R21 EB003164NIDDK NIH HHS P01 DK032094NIDDK NIH HHS P01-DK032094NIDDK NIH HHS P30 DK090969NIDDK NIH HHS P30-DK090969
6 · The paper itself

Abstract

A macrophage engulfs another cell or foreign particle in an adhesive process that often activates myosin-II, unless the macrophage also engages "marker of self" CD47 that inhibits myosin. For many cell types, adhesion-induced activation of myosin-II is maximized by adhesion to a rigid rather than a flexible substrate. Here we demonstrate that rigidity of a phagocytosed cell also hyperactivates myosin-II, which locally overwhelms self-signaling at a phagocytic synapse. Cell stiffness is one among many factors including shape that changes in erythropoiesis, in senescence and in diseases ranging from inherited anemias and malaria to cancer. Controlled stiffening of normal human red blood cells (RBCs) in different shapes does not compromise CD47's interaction with the macrophage self-recognition receptor signal regulatory protein alpha (SIRPA). Uptake of antibody-opsonized RBCs is always fastest with rigid RBC discocytes, which also show that maximal active myosin-II at the synapse can dominate self-signaling by CD47. Rigid but rounded RBC stomatocytes signal self better than rigid RBC discocytes, highlighting the effects of shape on CD47 inhibition. Physical properties of phagocytic targets thus regulate self signaling, as is relevant to erythropoiesis, to clearance of rigid RBCs after blood storage, clearance of rigid pathological cells such as thalassemic or sickle cells, and even to interactions of soft/stiff cancer cells with macrophages.

Indexed as

Antigens, DifferentiationCD47 AntigenCell CommunicationCells, CulturedCell ShapeErythrocytesFlow CytometryHumansIntercellular JunctionsNonmuscle Myosin Type IIAPhagocytosisPhosphorylationReceptors, ImmunologicAntigens, DifferentiationCD47 AntigenNonmuscle Myosin Type IIAReceptors, ImmunologicSIRPA protein, human

Identifiers

PMID25411427
PMCPMC4296014
OpenAlexW1992252296

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.