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]
© 2015 Shastri et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/
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 Type:||Refereed Article|
|Keywords:||heparin, HPLC, carbohydrates, anticoagulant|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Pharmacology and pharmaceutical sciences|
|Research Field:||Pharmaceutical sciences|
|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)|
|Web of Science® Times Cited:||18|
|Downloads:||355 View Download Statistics|
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