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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 52, Issue 4


Increased plasma arginase activity in human sepsis: association with increased circulating neutrophils

Christabelle J. Darcy
  • Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
  • Other articles by this author:
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/ Tonia Woodberry / Joshua S. Davis
  • Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
  • Infectious Diseases Department, Royal Darwin Hospital, Darwin, NT, Australia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kim A. Piera
  • Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
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/ Yvette R. McNeil
  • Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
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/ Youwei Chen
  • Division of Hematology-Oncology, Duke University and Veterans’ Affairs Medical Centers, Durham, NC, USA
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/ Tsin W. Yeo
  • Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
  • Infectious Diseases Department, Royal Darwin Hospital, Darwin, NT, Australia
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  • De Gruyter OnlineGoogle Scholar
/ J. Brice Weinberg
  • Division of Hematology-Oncology, Duke University and Veterans’ Affairs Medical Centers, Durham, NC, USA
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/ Nicholas M. Anstey
  • Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
  • Infectious Diseases Department, Royal Darwin Hospital, Darwin, NT, Australia
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  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-10-29 | DOI: https://doi.org/10.1515/cclm-2013-0698


Background: The pathophysiology of sepsis is incompletely understood. Impaired bioavailability of L-arginine, the substrate for NO synthesis, is linked to sepsis severity, and plasma arginase has been linked to hypoargininemia in other disease states. Circulating neutrophils are increased in sepsis and constitutively express arginase. We investigated whether plasma arginase activity is increased in human sepsis and whether this is associated with neutrophil numbers and activation.

Methods: We used HPLC and a radiometric assay to evaluate plasma amino acid concentrations and plasma arginase activity. The relationships between plasma arginase activity, neutrophil count, neutrophil activity and plasma L-arginine and arginine metabolites were evaluated in 44 sepsis patients and 25 controls.

Results: Plasma arginase activity was increased in sepsis patients, correlated with neutrophil count (r=0.44; p=0.003), but was independent of sepsis severity (SOFA or APACHE II score). Plasma HNP1-3 correlated with neutrophil count (r=0.31; p=0.04), was elevated in shock (median 180 ng/mL vs. 83 ng/mL sepsis without shock, p=0.0006) and correlated with SOFA score. Sepsis patients with high neutrophil counts had significantly higher plasma HNP1-3 and arginase activity and lower plasma L-arginine concentrations than those with lower neutrophil counts and controls.

Conclusions: Plasma arginase activity, potentially derived in part from neutrophil activation, is elevated in sepsis, and may contribute to impaired bioavailability of L-arginine in sepsis.

Keywords: hypoargininemia; L-arginine; plasma arginase activity; sepsis


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About the article

Corresponding author: Tonia Woodberry, Menzies School of Health Research, PO Box 41096, Casuarina, NT 0811, Australia, Phone: +61 8 8922 8196, Fax: +61 8 8927 5187, E-mail:

aChristabelle J. Darcy and Tonia Woodberry contributed equally.

Received: 2013-08-27

Accepted: 2013-10-08

Published Online: 2013-10-29

Published in Print: 2014-04-01

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 52, Issue 4, Pages 573–581, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2013-0698.

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