Evidence map›Paper›PMID 17673941›Full record

ArticleMolecular medicine (Cambridge, Mass.)

Fractalkine-induced MFG-E8 leads to enhanced apoptotic cell clearance by macrophages.

Michael Miksa, Dhruv Amin, Rongqian Wu, Thanjavur S Ravikumar, Ping Wang

Open access · goldAbstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

74 citing papers in PubMed, 117 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. The battle within: cell death by phagocytosis in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. The Apoptosis Paradox in Cancer.International journal of molecular sciences · 2022
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

14 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

5 authors at 3 institutions in 1 country.

Michael MiksaThe Feinstein Institute for Medical Research, Manhasset, New York 11030, USA.
Dhruv Amin
Rongqian Wu
Thanjavur S Ravikumar
Ping Wang
North Shore University Hospital · USLong Island Jewish Medical Center · USFeinstein Institute for Medical Research · US

Funding

IMPROVEMENT OF ORGAN FUNCTION AFTER SEVERE HYPOVOLEMIAR01HL076179 · NHLBI · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI PING WANG · 2004 to 2026
$7.6M
SEPSIS--MEDIATORS AND CARDIOVASCULAR RESPONSESR01GM057468 · NIGMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI WANG, PING · 1998 to 2015
$3.8M
NHLBI NIH HHS R01 HL076179NIGMS NIH HHS R01 GM057468
6 · The paper itself

Abstract

Clearance of apoptotic cells is crucial to maintain cellular function under normal and pathological conditions. We have recently shown that administration of immature dendritic cell-derived exosomes to septic animals promotes phagocytosis of apoptotic cells and improves survival by providing milk fat globule epidermal growth factor-factor VIII (MFG-E8). MFG-E8 acts as an opsonin for apoptotic cells to be engulfed by phagocytosis. In the present study we investigated whether the CX(3)C-chemokine fractalkine (CX(3)CL1) promotes apoptotic cell clearance through the induction of MFG-E8 in peritoneal macrophages. Cultured rat peritoneal macrophages (pMphi) and RAW264.7 macrophages were stimulated with LPS and CX(3)CL1. MFG-E8 expression was assessed by Western blot, cytokine secretion was assessed by ELISA, and phagocytosis of apoptotic thymocytes was determined by microscopy. For in vivo studies, cecal ligation and puncture (CLP) was used to induce sepsis in rats and mice. LPS significantly decreased MFG-E8 levels and phagocytosis of apoptotic cells, whereas CX(3)CL1 induced MFG-E8 expression in both nonstimulated and LPS-stimulated pMphi, without affecting TNF-alpha and IL-6 release. Anti-MFG-E8 blocking antibodies completely abrogated the prophagocytic effect of CX(3)CL1. Twenty hours after the induction of sepsis in rats via CLP, plasma CX(3)CL1 levels as well as MFG-E8 production in peritoneal macrophages decreased by 21% and 56%, respectively. Administration of CX(3)CL1 on the other hand induced MFG-E8 and prevented tissue injury. We conclude that CX(3)CL1 induces MFG-E8 in vitro and in vivo and enhances clearance of apoptotic cells in an MFG-E8-dependent manner. These findings suggest a possible novel treatment for patients in sepsis.

Indexed as

AnimalsApoptosisBlotting, WesternCell LineChemokine CX3CL1Enzyme-Linked Immunosorbent AssayMacrophages, PeritonealMaleMilk ProteinsPhagocytosisRatsRats, Sprague-DawleyRecombinant ProteinsChemokine CX3CL1Cx3cl1 protein, ratMilk ProteinsRecombinant Proteins

Identifiers

PMID17673941
PMCPMC1936982
OpenAlexW2415209394

What OpenQuestion holds

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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.