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Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study

BACKGROUND: Plasma hyaluronan concentrations are increased during sepsis but underlying mechanisms leading to high plasma hyaluronan concentration are poorly understood. In this study we evaluate the roles of plasma hyaluronan, effective plasma hyaluronidase (HYAL) activity and its endogenous plasma...

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Autores principales: van der Heijden, Jaap, Kolliopoulos, Constantinos, Skorup, Paul, Sallisalmi, Marko, Heldin, Paraskevi, Hultström, Michael, Tenhunen, Jyrki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502523/
https://www.ncbi.nlm.nih.gov/pubmed/34632531
http://dx.doi.org/10.1186/s40635-021-00418-3
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author van der Heijden, Jaap
Kolliopoulos, Constantinos
Skorup, Paul
Sallisalmi, Marko
Heldin, Paraskevi
Hultström, Michael
Tenhunen, Jyrki
author_facet van der Heijden, Jaap
Kolliopoulos, Constantinos
Skorup, Paul
Sallisalmi, Marko
Heldin, Paraskevi
Hultström, Michael
Tenhunen, Jyrki
author_sort van der Heijden, Jaap
collection PubMed
description BACKGROUND: Plasma hyaluronan concentrations are increased during sepsis but underlying mechanisms leading to high plasma hyaluronan concentration are poorly understood. In this study we evaluate the roles of plasma hyaluronan, effective plasma hyaluronidase (HYAL) activity and its endogenous plasma inhibition in clinical and experimental sepsis. We specifically hypothesized that plasma HYAL acts as endothelial glycocalyx shedding enzyme, sheddase. METHODS: Plasma hyaluronan, effective HYAL activity and HYAL inhibition were measured in healthy volunteers (n = 20), in patients with septic shock (n = 17, day 1 and day 4), in patients with acute pancreatitis (n = 7, day 1 and day 4) and in anesthetized and mechanically ventilated pigs (n = 16). Sixteen pigs were allocated (unblinded, open label) into three groups: Sepsis-1 with infusion of live Escherichia coli (E. coli) 1 × 10(8) CFU/h of 12 h (n = 5), Sepsis-2 with infusion of E. coli 1 × 10(8) CFU/h of 6 h followed by 1 × 10(9) CFU/h of the remaining 6 h (n = 5) or Control with no E. coli infusion (n = 6). RESULTS: In experimental E. coli porcine sepsis and in time controls, plasma hyaluronan increases with concomitant decrease in effective plasma HYAL activity and increase of endogenous HYAL inhibition. Plasma hyaluronan increased in patients with septic shock but not in acute pancreatitis. Effective plasma HYAL was lower in septic shock and acute pancreatitis as compared to healthy volunteers, while plasma HYAL inhibition was only increased in septic shock. CONCLUSION: Elevated plasma hyaluronan levels coincided with a concomitant decrease in effective plasma HYAL activity and increase of endogenous plasma HYAL inhibition both in experimental and clinical sepsis. In acute pancreatitis, effective plasma HYAL activity was decreased which was not associated with increased plasma hyaluronan concentrations or endogenous HYAL inhibition. The results suggest that plasma HYAL does not act as sheddase in sepsis or pancreatitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40635-021-00418-3.
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spelling pubmed-85025232021-10-12 Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study van der Heijden, Jaap Kolliopoulos, Constantinos Skorup, Paul Sallisalmi, Marko Heldin, Paraskevi Hultström, Michael Tenhunen, Jyrki Intensive Care Med Exp Research Articles BACKGROUND: Plasma hyaluronan concentrations are increased during sepsis but underlying mechanisms leading to high plasma hyaluronan concentration are poorly understood. In this study we evaluate the roles of plasma hyaluronan, effective plasma hyaluronidase (HYAL) activity and its endogenous plasma inhibition in clinical and experimental sepsis. We specifically hypothesized that plasma HYAL acts as endothelial glycocalyx shedding enzyme, sheddase. METHODS: Plasma hyaluronan, effective HYAL activity and HYAL inhibition were measured in healthy volunteers (n = 20), in patients with septic shock (n = 17, day 1 and day 4), in patients with acute pancreatitis (n = 7, day 1 and day 4) and in anesthetized and mechanically ventilated pigs (n = 16). Sixteen pigs were allocated (unblinded, open label) into three groups: Sepsis-1 with infusion of live Escherichia coli (E. coli) 1 × 10(8) CFU/h of 12 h (n = 5), Sepsis-2 with infusion of E. coli 1 × 10(8) CFU/h of 6 h followed by 1 × 10(9) CFU/h of the remaining 6 h (n = 5) or Control with no E. coli infusion (n = 6). RESULTS: In experimental E. coli porcine sepsis and in time controls, plasma hyaluronan increases with concomitant decrease in effective plasma HYAL activity and increase of endogenous HYAL inhibition. Plasma hyaluronan increased in patients with septic shock but not in acute pancreatitis. Effective plasma HYAL was lower in septic shock and acute pancreatitis as compared to healthy volunteers, while plasma HYAL inhibition was only increased in septic shock. CONCLUSION: Elevated plasma hyaluronan levels coincided with a concomitant decrease in effective plasma HYAL activity and increase of endogenous plasma HYAL inhibition both in experimental and clinical sepsis. In acute pancreatitis, effective plasma HYAL activity was decreased which was not associated with increased plasma hyaluronan concentrations or endogenous HYAL inhibition. The results suggest that plasma HYAL does not act as sheddase in sepsis or pancreatitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40635-021-00418-3. Springer International Publishing 2021-10-11 /pmc/articles/PMC8502523/ /pubmed/34632531 http://dx.doi.org/10.1186/s40635-021-00418-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
van der Heijden, Jaap
Kolliopoulos, Constantinos
Skorup, Paul
Sallisalmi, Marko
Heldin, Paraskevi
Hultström, Michael
Tenhunen, Jyrki
Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study
title Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study
title_full Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study
title_fullStr Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study
title_full_unstemmed Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study
title_short Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study
title_sort plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502523/
https://www.ncbi.nlm.nih.gov/pubmed/34632531
http://dx.doi.org/10.1186/s40635-021-00418-3
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