Evidence map›Paper›PMID 23878196›Full record

ArticleThe Journal of biological chemistry2013

Immobilized heavy chain-hyaluronic acid polarizes lipopolysaccharide-activated macrophages toward M2 phenotype.

Hua He, Suzhen Zhang, Sean Tighe, Ji Son, Scheffer C G Tseng

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

86 citing papers in PubMed, 155 citations in OpenAlex.

  1. An open-label trial of cryopreserved human umbilical cord in the treatment of complex diabetic foot ulcers complicated by osteomyelitis.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2019
    Trial
  2. Trial
  3. Trial
  4. Trial
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. CD44 signaling in skin wound healing and regeneration.Journal of translational medicine · 2025
    Review
  15. Article
  16. Development of Amniotic Epithelial Stem Cells Secretome-LoadedACS applied materials & interfaces · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Article

26 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 1 institution in 1 country.

Hua HeFrom the TissueTech, Inc.
Suzhen ZhangFrom the TissueTech, Inc.
Sean TigheFrom the TissueTech, Inc.
Ji Sonthe Ocular Surface Research Education Foundation, and.
Scheffer C G TsengFrom the TissueTech, Inc.,; the Ocular Surface Research Education Foundation, and; the Ocular Surface Center, Miami, Florida 33173. Electronic address: stseng@ocularsurface.com.
Ocular Surface Center · US

Funding

VITAMIN A AND CONJUNCTIVAL TRANSDIFFERENTIATIONR01EY006819 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI TSENG, SCHEFFER CG · 1986 to 2020
$6.7M
Phase II: Anti-inflammatory and Anti-scarring Actions of Amniotic Membrane ExtraR44EY017497 · NEI · TISSUETECH, INC. · PI TSENG, SCHEFFER CG · 2010 to 2011
$936k
Anti-angiogenesis of HC-HA Covalent Complex and PTX3 Purified from Fetal MembraneR43EY021045 · NEI · TISSUETECH, INC. · PI TSENG, SCHEFFER CG · 2011 to 2011
$240k
NEI NIH HHS R01 EY006819NEI NIH HHS R01 EY06819NEI NIH HHS R43 EY021045NEI NIH HHS R43 EY21045NEI NIH HHS R44 EY017497
6 · The paper itself

Abstract

Despite the known anti-inflammatory effect of amniotic membrane, its action mechanism remains largely unknown. HC-HA complex (HC-HA) purified from human amniotic membrane consists of high molecular weight hyaluronic acid (HA) covalently linked to the heavy chain (HC) 1 of inter-α-trypsin inhibitor. In this study, we show that soluble HC-HA also contained pentraxin 3 and induced the apoptosis of both formyl-Met-Leu-Phe or LPS-activated neutrophils and LPS-activated macrophages while not affecting the resting cells. This enhanced apoptosis was caused by the inhibition of cell adhesion, spreading, and proliferation caused by HC-HA binding of LPS-activated macrophages and preventing adhesion to the plastic surface. Preferentially, soluble HC-HA promoted phagocytosis of apoptotic neutrophils in resting macrophages, whereas immobilized HC-HA promoted phagocytosis in LPS-activated macrophages. Upon concomitant LPS stimulation, immobilized HC-HA but not HA polarized macrophages toward the M2 phenotype by down-regulating IRF5 protein and preventing its nuclear localization and by down-regulating IL-12, TNF-α, and NO synthase 2. Additionally, IL-10, TGF-β1, peroxisome proliferator-activated receptor γ, LIGHT (TNF superfamily 14), and sphingosine kinase-1 were up-regulated, and such M2 polarization was dependent on TLR ligation. Collectively, these data suggest that HC-HA is a unique matrix component different from HA and uses multiple mechanisms to suppress M1 while promoting M2 phenotype. This anti-inflammatory action of HC-HA is highly desirable to promote wound healing in diseases heightened by unsuccessful transition from M1 to M2 phenotypes.

Indexed as

Adjuvants, ImmunologicAnimalsCell LineCytokinesDown-RegulationHumansHyaluronic AcidInterferon Regulatory FactorsLipopolysaccharidesMacrophage ActivationMacrophagesMiceNeutrophilsNitric Oxide Synthase Type IIPhagocytosisPPAR gammaAdjuvants, ImmunologicCytokinesHyaluronic AcidInterferon Regulatory FactorsIRF5 protein, humanIrf5 protein, mouseLipopolysaccharidesNitric Oxide Synthase Type IINOS2 protein, humanNos2 protein, mousePPAR gammaToll-Like ReceptorsAmniotic Membrane, HC-HA, M1/M2 PhenotypeApoptosisCell AdhesionCell ProliferationInflammationMacrophagesPhagocytosis

Identifiers

PMID23878196
PMCPMC3764786
OpenAlexW1968667554

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.