Evidence map›Paper›PMID 18662971›Full record

ArticleJournal of leukocyte biology2008

An engineered monomer of CCL2 has anti-inflammatory properties emphasizing the importance of oligomerization for chemokine activity in vivo.

Tracy M Handel, Zoë Johnson, David H Rodrigues, Adriana C Dos Santos, Rocco Cirillo, Valeria Muzio, Simona Riva, Matthias Mack, Maud Déruaz, Frédéric Borlat and 4 more

Open access · greenAbstract read
In one paragraph

Article in Journal of leukocyte biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 68 citations in OpenAlex.

  1. Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023
    Review
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  10. Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes.Journal of immunology (Baltimore, Md. : 1950) · 2015
    Article
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  13. SerpinB2 is critical to Th2 immunity against enteric nematode infection.Journal of immunology (Baltimore, Md. : 1950) · 2013
    Article
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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

14 authors at 4 institutions in 4 countries.

Tracy M HandelMerck Serono Geneva Research Centre, Geneva, Switzerland.
Zoë Johnson
David H Rodrigues
Adriana C Dos Santos
Rocco Cirillo
Valeria Muzio
Simona Riva
Matthias Mack
Maud Déruaz
Frédéric Borlat
Pierre-Alain Vitte
Timothy N C Wells
Mauro M Teixeira
Amanda E I Proudfoot
Merck Serono (Switzerland) · CHUniversidade Federal de Minas Gerais · BRUniversity of California, San Diego · USUniversity of Regensburg · DE

Funding

STRUCTURE OF MACROPHAGE CHEMOTACTIC ACTIVATING PROTEINSR01AI037113 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HANDEL, TRACY M · 1995 to 2015
$5.2M
NIAID NIH HHS R01 AI037113NIAID NIH HHS R01-AI37113
6 · The paper itself

Abstract

We demonstrated recently that P8A-CCL2, a monomeric variant of the chemokine CCL2/MCP-1, is unable to induce cellular recruitment in vivo, despite full activity in vitro. Here, we show that this variant is able to inhibit CCL2 and thioglycollate-mediated recruitment of leukocytes into the peritoneal cavity and recruitment of cells into lungs of OVA-sensitized mice. This anti-inflammatory activity translated into a reduction of clinical score in the more complex inflammatory model of murine experimental autoimmune encephalomyelitis. Several hypotheses for the mechanism of action of P8A-CCL2 were tested. Plasma exposure following s.c. injection is similar for P8A-CCL2 and wild-type (WT) CCL2, ruling out the hypothesis that P8A-CCL2 disrupts the chemokine gradient through systemic exposure. P8A-CCL2 and WT induce CCR2 internalization in vitro and in vivo; CCR2 then recycles to the cell surface, but the cells remain refractory to chemotaxis in vitro for several hours. Although the response to P8A-CCL2 is similar to WT, this finding is novel and suggests that despite the presence of the receptor on the cell surface, coupling to the signaling machinery is retarded. In contrast to CCL2, P8A-CCL2 does not oligomerize on glycosaminoglycans (GAGs). However, it retains the ability to bind GAGs and displaces endogenous JE (murine MCP-1) from endothelial surfaces. Intravital microscopy studies indicate that P8A-CCL2 prevents leukocyte adhesion, while CCL2 has no effect, and this phenomenon may be related to the mechanism. These results suggest that oligomerization-deficient chemokines can exhibit anti-inflammatory properties in vivo and may represent new therapeutic modalities.

Indexed as

AnimalsAnti-Inflammatory AgentsBrainCerebrovascular CirculationChemokine CCL2ChemokinesChemotaxis, LeukocyteFemaleGenetic EngineeringHeparinImmunizationLeukocytesMiceMice, Inbred BALB COvalbuminThioglycolatesAnti-Inflammatory AgentsCcl2 protein, mouseChemokine CCL2ChemokinesHeparinOvalbuminThioglycolates

Identifiers

PMID18662971
PMCPMC2538597
OpenAlexW2109906269

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.