ArticleJournal of leukocyte biology2008
An engineered monomer of CCL2 has anti-inflammatory properties emphasizing the importance of oligomerization for chemokine activity in vivo.
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.
What it found
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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.
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.
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Who cites it
31 citing papers in PubMed, 68 citations in OpenAlex.
- Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.International journal of molecular sciences · 2023Review
- Disruption of monocyte-macrophage differentiation and trafficking by a heme analog during active inflammation.Mucosal immunology · 2022Article
- Neutrophil Extracellular Traps Induce MCP-1 at the Culprit Site in ST-Segment Elevation Myocardial Infarction.Frontiers in cell and developmental biology · 2020Article
- Targeting Chemokine-Glycosaminoglycan Interactions to Inhibit Inflammation.Frontiers in immunology · 2020Review
- More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis.Frontiers in immunology · 2019Review
- Glycosaminoglycan Interactions with Chemokines Add Complexity to a Complex System.Pharmaceuticals (Basel, Switzerland) · 2017Review
- CCL2 nitration is a negative regulator of chemokine-mediated inflammation.Scientific reports · 2017Article
- Modeling leukocyte trafficking at the human blood-nerve barrier in vitro and in vivo geared towards targeted molecular therapies for peripheral neuroinflammation.Journal of neuroinflammation · 2016Review
- Chemokine and chemokine receptor structure and interactions: implications for therapeutic strategies.Immunology and cell biology · 2015Review
- Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme.Journal of molecular biology · 2015Article
- Multiple glycosaminoglycan-binding epitopes of monocyte chemoattractant protein-3/CCL7 enable it to function as a non-oligomerizing chemokine.The Journal of biological chemistry · 2014Article
- SerpinB2 is critical to Th2 immunity against enteric nematode infection.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Tyrosine sulfation of chemokine receptor CCR2 enhances interactions with both monomeric and dimeric forms of the chemokine monocyte chemoattractant protein-1 (MCP-1).The Journal of biological chemistry · 2013Article
- Structure-based design of decoy chemokines as a way to explore the pharmacological potential of glycosaminoglycans.British journal of pharmacology · 2012Review
- Monocyte Chemoattractant Protein 1 (MCP-1) in obesity and diabetes.Cytokine · 2012 · on this mapReview
- The CCL2 synthesis inhibitor bindarit targets cells of the neurovascular unit, and suppresses experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2012Article
- CCR2 acts as scavenger for CCL2 during monocyte chemotaxis.PloS one · 2012Article
- Chemokines: established and novel targets in atherosclerosis.EMBO molecular medicine · 2011Review
- The level of CD147 expression correlates with cyclophilin-induced signalling and chemotaxis.BMC research notes · 2011Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
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.
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Registered trials
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.