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Non-anticoagulant fractions of enoxaparin suppress inflammatory cytokine release from peripheral blood mononuclear cells of allergic asthmatic individuals
Citation
Shastri, MD and Stewart, N and Horne, J and Zaidi, STR and Sohal, SS and Peterson, GM and Korner, H and Gueven, N and Patel, RP, Non-anticoagulant fractions of enoxaparin suppress inflammatory cytokine release from peripheral blood mononuclear cells of allergic asthmatic individuals, PLoS One, 10, (6) Article e0128803. ISSN 1932-6203 (2015) [Refereed Article]
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Copyright Statement
© 2015 Shastri et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/
DOI: doi:10.1371/journal.pone.0128803
Abstract
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).
Conclusions 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.
Item Details
Item Type: | Refereed Article |
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Keywords: | heparin, HPLC, carbohydrates, anticoagulant |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Pharmacology and pharmaceutical sciences |
Research Field: | Pharmaceutical sciences |
Objective Division: | Health |
Objective Group: | Public health (excl. specific population health) |
Objective Field: | Public health (excl. specific population health) not elsewhere classified |
UTAS Author: | Shastri, MD (Mr Madhur Shastri) |
UTAS Author: | Stewart, N (Dr Niall Stewart) |
UTAS Author: | Horne, J (Dr James Horne) |
UTAS Author: | Zaidi, STR (Dr Tabish Razi Zaidi) |
UTAS Author: | Sohal, SS (Dr Sukhwinder Sohal) |
UTAS Author: | Peterson, GM (Professor Gregory Peterson) |
UTAS Author: | Korner, H (Professor Heinrich Korner) |
UTAS Author: | Gueven, N (Dr Nuri Guven) |
UTAS Author: | Patel, RP (Dr Rahul Patel) |
ID Code: | 101020 |
Year Published: | 2015 |
Web of Science® Times Cited: | 20 |
Deposited By: | Pharmacy |
Deposited On: | 2015-06-07 |
Last Modified: | 2017-11-02 |
Downloads: | 366 View Download Statistics |
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