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Non-anticoagulant fractions of enoxaparin suppress inflammatory cytokine release from peripheral blood mononuclear cells of allergic asthmatic individuals

PLoS ONE, ISSN: 1932-6203, Vol: 10, Issue: 6, Page: e0128803
2015
  • 26
    Citations
  • 0
    Usage
  • 20
    Captures
  • 0
    Mentions
  • 560
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    26
  • Captures
    20
  • Social Media
    560
    • Shares, Likes & Comments
      560
      • Facebook
        560

Article Description

Background: Enoxaparin, a low-molecular-weight heparin, is known to possess anti-inflammatory properties. However, its clinical exploitation as an anti-inflammatory agent is hampered by its anticoagulant effect and the associated risk of bleeding. Objective: The aim of the current study was to examine the ability of non-anticoagulant fractions of enoxaparin to inhibit the release of key inflammatory cytokines in primed peripheral blood mononuclear cells derived from allergic mild asthmatics. Methods: Peripheral blood mononuclear cells from allergic asthmatics were activated with phytohaemag glutinin (PHA), concanavalin-A (ConA) or phorbol 12-myristate 13-acetate (PMA) in the presence or absence of enoxaparin fractions before cytokine levels were quantified using specific cytokine bead arrays. Together with nuclear magnetic resonance analysis, time-dependent and target-specific effects of enoxaparin fractions were used to elucidate structural determinants for their anti-inflammatory effect and gain mechanistic insights into their anti-inflammatory activity. Results: Two non-anticoagulant fractions of enoxaparin were identified that significantly inhibited T-cell activation. A disaccharide fraction of enoxaparin inhibited the release of IL-4, IL-5, IL-13 and TNF-α by more than 57% while a tetrasaccharide fraction was found to inhibit the release of tested cytokines by more than 68%. Our data suggest that the observed response is likely to be due to an interaction of 6-O-sulfated tetrasaccharide with cellular receptor(s). Conclusion and Clinical Relevance: The two identified anti-inflammatory fractions lacked anticoagulant activity and are therefore not associated with risk of bleeding. The findings highlight the potential therapeutic use of enoxaparin-derived fractions, in particular tetrasaccharide, in patients with chronic inflammatory disorders.

Bibliographic Details

http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84934971848&origin=inward; http://dx.doi.org/10.1371/journal.pone.0128803; http://www.ncbi.nlm.nih.gov/pubmed/26046354; https://dx.plos.org/10.1371/journal.pone.0128803.g002; http://dx.doi.org/10.1371/journal.pone.0128803.g002; https://dx.plos.org/10.1371/journal.pone.0128803.g007; http://dx.doi.org/10.1371/journal.pone.0128803.g007; https://dx.plos.org/10.1371/journal.pone.0128803; https://dx.plos.org/10.1371/journal.pone.0128803.g001; http://dx.doi.org/10.1371/journal.pone.0128803.g001; https://dx.plos.org/10.1371/journal.pone.0128803.g006; http://dx.doi.org/10.1371/journal.pone.0128803.g006; https://dx.plos.org/10.1371/journal.pone.0128803.g005; http://dx.doi.org/10.1371/journal.pone.0128803.g005; https://dx.plos.org/10.1371/journal.pone.0128803.g004; http://dx.doi.org/10.1371/journal.pone.0128803.g004; https://dx.plos.org/10.1371/journal.pone.0128803.g003; http://dx.doi.org/10.1371/journal.pone.0128803.g003; https://dx.doi.org/10.1371/journal.pone.0128803; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128803; https://dx.doi.org/10.1371/journal.pone.0128803.g001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0128803.g001; https://dx.doi.org/10.1371/journal.pone.0128803.g007; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0128803.g007; https://dx.doi.org/10.1371/journal.pone.0128803.g004; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0128803.g004; https://dx.doi.org/10.1371/journal.pone.0128803.g002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0128803.g002; https://dx.doi.org/10.1371/journal.pone.0128803.g005; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0128803.g005; https://dx.doi.org/10.1371/journal.pone.0128803.g006; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0128803.g006; https://dx.doi.org/10.1371/journal.pone.0128803.g003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0128803.g003; http://dx.plos.org/10.1371/journal.pone.0128803.g007; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128803; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0128803&type=printable; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pone.0128803; http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0128803&type=printable; http://dx.plos.org/10.1371/journal.pone.0128803.g003; http://dx.plos.org/10.1371/journal.pone.0128803.g005; http://dx.plos.org/10.1371/journal.pone.0128803.g006; http://dx.plos.org/10.1371/journal.pone.0128803; http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0128803; http://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0128803; http://dx.plos.org/10.1371/journal.pone.0128803.g002; http://dx.plos.org/10.1371/journal.pone.0128803.g001; http://dx.plos.org/10.1371/journal.pone.0128803.g004

Madhur D. Shastri; Niall Stewart; James Horne; Syed Tabish R. Zaidi; Sukhwinder Singh Sohal; Gregory M. Peterson; Heinrich Korner; Nuri Gueven; Rahul P. Patel; Muriel Moser

Public Library of Science (PLoS)

Multidisciplinary

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