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
- 26Citations
- 20Captures
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Metrics Details
- Citations26
- Citation Indexes26
- 26
- CrossRef20
- Captures20
- Readers20
- 20
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
10.1371/journal.pone.0128803; 10.1371/journal.pone.0128803.g002; 10.1371/journal.pone.0128803.g007; 10.1371/journal.pone.0128803.g001; 10.1371/journal.pone.0128803.g006; 10.1371/journal.pone.0128803.g005; 10.1371/journal.pone.0128803.g004; 10.1371/journal.pone.0128803.g003
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