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The accumulation of circulating histones on heparan sulphate in the capillary glycocalyx of the lungs

Paper ID Volume ID Publish Year Pages File Format Full-Text
6366 485 2013 7 PDF Available
Title
The accumulation of circulating histones on heparan sulphate in the capillary glycocalyx of the lungs
Abstract

Recent findings on the role of circulating histone proteins in mediating acute lung injury prompted us to investigate whether there is a specific mechanism for accumulation of histones in the lungs. Binding sites for polycations are already known in the vasculature of the lungs, and we postulated that these could also be involved in histone accumulation, since histones have a high content of positively charged amino acids. Using a histone-coated colloid of a radiolabelled nanocomposite to track histone biodistribution with imaging techniques, it was found that histones bind avidly in the lungs of rabbits after intravenous injection. Blocking experiments with competing polycations in vivo characterised histone lung binding as dependent on a charge interaction with microvessel polyanions. Pretreatment of rabbits with a specific heparinase confirmed that the lung binding sites consist of heparan sulphate in the endothelial glycocalyx. A range of heparan sulphate analogues was accordingly shown to prevent histone accumulation in the lungs by neutralising histones in blood. These findings provide a rational basis for the design of polyanions that can prevent accumulation of cytotoxic histones in the lungs and thereby intervene at an early key step in the development of acute lung injury.

Keywords
Histones; Heparan sulphate; Lung endothelium; Acute lung injury
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The accumulation of circulating histones on heparan sulphate in the capillary glycocalyx of the lungs
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 22, July 2013, Pages 5670–5676
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us