Cargando…

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

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 cfD...

Descripción completa

Detalles Bibliográficos
Autores principales: Dinsdale, R. J., Hazeldine, J., Al Tarrah, K., Hampson, P., Devi, A., Ermogenous, C., Bamford, A. L., Bishop, J., Watts, S., Kirkman, E., Dalle Lucca, J. J., Midwinter, M., Woolley, T., Foster, M., Lord, J. M., Moiemen, N., Harrison, P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079039/
https://www.ncbi.nlm.nih.gov/pubmed/31502663
http://dx.doi.org/10.1002/bjs.11310
_version_ 1783507745847115776
author Dinsdale, R. J.
Hazeldine, J.
Al Tarrah, K.
Hampson, P.
Devi, A.
Ermogenous, C.
Bamford, A. L.
Bishop, J.
Watts, S.
Kirkman, E.
Dalle Lucca, J. J.
Midwinter, M.
Woolley, T.
Foster, M.
Lord, J. M.
Moiemen, N.
Harrison, P.
author_facet Dinsdale, R. J.
Hazeldine, J.
Al Tarrah, K.
Hampson, P.
Devi, A.
Ermogenous, C.
Bamford, A. L.
Bishop, J.
Watts, S.
Kirkman, E.
Dalle Lucca, J. J.
Midwinter, M.
Woolley, T.
Foster, M.
Lord, J. M.
Moiemen, N.
Harrison, P.
author_sort Dinsdale, R. J.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7079039
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley & Sons, Ltd
record_format MEDLINE/PubMed
spelling pubmed-70790392020-03-19 Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury Dinsdale, R. J. Hazeldine, J. Al Tarrah, K. Hampson, P. Devi, A. Ermogenous, C. Bamford, A. L. Bishop, J. Watts, S. Kirkman, E. Dalle Lucca, J. J. Midwinter, M. Woolley, T. Foster, M. Lord, J. M. Moiemen, N. Harrison, P. Br J Surg Original Articles 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. John Wiley & Sons, Ltd 2019-09-10 2020-03 /pmc/articles/PMC7079039/ /pubmed/31502663 http://dx.doi.org/10.1002/bjs.11310 Text en © 2019 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Dinsdale, R. J.
Hazeldine, J.
Al Tarrah, K.
Hampson, P.
Devi, A.
Ermogenous, C.
Bamford, A. L.
Bishop, J.
Watts, S.
Kirkman, E.
Dalle Lucca, J. J.
Midwinter, M.
Woolley, T.
Foster, M.
Lord, J. M.
Moiemen, N.
Harrison, P.
Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury
title Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury
title_full Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury
title_fullStr Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury
title_full_unstemmed Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury
title_short Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury
title_sort dysregulation of the actin scavenging system and inhibition of dnase activity following severe thermal injury
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079039/
https://www.ncbi.nlm.nih.gov/pubmed/31502663
http://dx.doi.org/10.1002/bjs.11310
work_keys_str_mv AT dinsdalerj dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT hazeldinej dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT altarrahk dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT hampsonp dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT devia dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT ermogenousc dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT bamfordal dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT bishopj dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT wattss dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT kirkmane dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT dalleluccajj dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT midwinterm dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT woolleyt dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT fosterm dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT lordjm dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT moiemenn dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury
AT harrisonp dysregulationoftheactinscavengingsystemandinhibitionofdnaseactivityfollowingseverethermalinjury