Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury.

Dinsdale, R J and Hazeldine, J and Al Tarrah, K and Hampson, P and Devi, A and Ermogenous, C and Bamford, A L and Bishop, J and Watts, S and Kirkman, E and Dalle Lucca, J J and Midwinter, M and Woolley, T and Foster, M and Lord, J M and Moiemen, N and Harrison, P (2019) Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury. The British journal of surgery. ISSN 1365-2168. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

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Official URL: https://onlinelibrary.wiley.com/doi/full/10.1002/b...

Abstract

BACKGROUND

Circulating cell-free DNA (cfDNA) is not found in healthy subjects, but is readily detected after thermal injury and may contribute to the risk of multiple organ failure. The hypothesis was that a postburn reduction in DNase protein/enzyme activity could contribute to the increase in cfDNA following thermal injury.

METHODS

Patients with severe burns covering at least 15 per cent of total body surface area were recruited to a prospective cohort study within 24 h of injury. Blood samples were collected from the day of injury for 12 months.

RESULTS

Analysis of blood samples from 64 patients revealed a significant reduction in DNase activity on days 1-28 after injury, compared with healthy controls. DNase protein levels were not affected, suggesting the presence of an enzyme inhibitor. Further analysis revealed that actin (an inhibitor of DNase) was present in serum samples from patients but not those from controls, and concentrations of the actin scavenging proteins gelsolin and vitamin D-binding protein were significantly reduced after burn injury. In a pilot study of ten military patients with polytrauma, administration of blood products resulted in an increase in DNase activity and gelsolin levels.

CONCLUSION

The results of this study suggest a novel biological mechanism for the accumulation of cfDNA following thermal injury by which high levels of actin released by damaged tissue cause a reduction in DNase activity. Restoration of the actin scavenging system could therefore restore DNase activity, and reduce the risk of cfDNA-induced host tissue damage and thrombosis.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: WD Diseases and disorders of systemic, metabolic or environmental origin > WD400 Emergency medicine
WO Surgery
Divisions: Ambulatory Care > Dermatology
Planned IP Care > General Surgery
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Depositing User: Beth Connors
Date Deposited: 16 Sep 2019 13:35
Last Modified: 16 Sep 2019 13:35
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2394

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