Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study
Abstract 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 endogenou...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2021-10-01
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| Series: | Intensive Care Medicine Experimental |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40635-021-00418-3 |
| _version_ | 1823962949500272640 |
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| author | Jaap van der Heijden Constantinos Kolliopoulos Paul Skorup Marko Sallisalmi Paraskevi Heldin Michael Hultström Jyrki Tenhunen |
| author_facet | Jaap van der Heijden Constantinos Kolliopoulos Paul Skorup Marko Sallisalmi Paraskevi Heldin Michael Hultström Jyrki Tenhunen |
| author_sort | Jaap van der Heijden |
| collection | DOAJ |
| description | Abstract 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 × 108 CFU/h of 12 h (n = 5), Sepsis-2 with infusion of E. coli 1 × 108 CFU/h of 6 h followed by 1 × 109 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. |
| first_indexed | 2024-12-17T17:23:31Z |
| format | Article |
| id | doaj.art-64daced85443466cabcdcdc43af85351 |
| institution | Directory Open Access Journal |
| issn | 2197-425X |
| language | English |
| last_indexed | 2024-12-17T17:23:31Z |
| publishDate | 2021-10-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Intensive Care Medicine Experimental |
| spelling | doaj.art-64daced85443466cabcdcdc43af853512022-12-21T21:39:42ZengSpringerOpenIntensive Care Medicine Experimental2197-425X2021-10-019111110.1186/s40635-021-00418-3Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort studyJaap van der Heijden0Constantinos Kolliopoulos1Paul Skorup2Marko Sallisalmi3Paraskevi Heldin4Michael Hultström5Jyrki Tenhunen6Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala UniversityDepartment Medical Biochemistry and Microbiology, Uppsala UniversityDepartment of Medical Sciences, Section of Infectious Diseases, Uppsala UniversityDivision of Anaesthesia and Intensive Care Medicine, Intensive Care Units, Department of Surgery, Helsinki University HospitalDepartment Medical Biochemistry and Microbiology, Uppsala UniversityDepartment of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala UniversityDepartment of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala UniversityAbstract 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 × 108 CFU/h of 12 h (n = 5), Sepsis-2 with infusion of E. coli 1 × 108 CFU/h of 6 h followed by 1 × 109 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.https://doi.org/10.1186/s40635-021-00418-3HyaluronanHyaluronidaseHyaluronidase inhibitorSepsisPancreatitisGlycocalyx |
| spellingShingle | Jaap van der Heijden Constantinos Kolliopoulos Paul Skorup Marko Sallisalmi Paraskevi Heldin Michael Hultström Jyrki Tenhunen Plasma hyaluronan, hyaluronidase activity and endogenous hyaluronidase inhibition in sepsis: an experimental and clinical cohort study Intensive Care Medicine Experimental Hyaluronan Hyaluronidase Hyaluronidase inhibitor Sepsis Pancreatitis Glycocalyx |
| 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 | Hyaluronan Hyaluronidase Hyaluronidase inhibitor Sepsis Pancreatitis Glycocalyx |
| url | https://doi.org/10.1186/s40635-021-00418-3 |
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