Increased plasma arginase activity in human sepsis

association with increased circulating neutrophils

Christabelle Darcy, Tonia Woodberry, Joshua Davis, Kim Piera, Yvette McNeil, Youwei Chen, Tsin Yeo, J Brice Weinberg, Nicholas Anstey

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Abstract

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.
Original languageEnglish
Pages (from-to)573-581
Number of pages9
JournalClinical Chemistry and Laboratory Medicine
Volume52
Issue number4
Early online date2013
DOIs
Publication statusPublished - 2014

Fingerprint

Arginase
Human Activities
Sepsis
Neutrophils
Thermodynamic properties
Association reactions
Plasmas
Arginine
Neutrophil Activation
Biological Availability
Shock
Chemical activation
APACHE
Metabolites
Assays
High Pressure Liquid Chromatography

Cite this

Darcy, Christabelle ; Woodberry, Tonia ; Davis, Joshua ; Piera, Kim ; McNeil, Yvette ; Chen, Youwei ; Yeo, Tsin ; Weinberg, J Brice ; Anstey, Nicholas. / Increased plasma arginase activity in human sepsis : association with increased circulating neutrophils. In: Clinical Chemistry and Laboratory Medicine. 2014 ; Vol. 52, No. 4. pp. 573-581.
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abstract = "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.",
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Increased plasma arginase activity in human sepsis : association with increased circulating neutrophils. / Darcy, Christabelle; Woodberry, Tonia; Davis, Joshua; Piera, Kim; McNeil, Yvette; Chen, Youwei; Yeo, Tsin; Weinberg, J Brice; Anstey, Nicholas.

In: Clinical Chemistry and Laboratory Medicine, Vol. 52, No. 4, 2014, p. 573-581.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Increased plasma arginase activity in human sepsis

T2 - association with increased circulating neutrophils

AU - Darcy, Christabelle

AU - Woodberry, Tonia

AU - Davis, Joshua

AU - Piera, Kim

AU - McNeil, Yvette

AU - Chen, Youwei

AU - Yeo, Tsin

AU - Weinberg, J Brice

AU - Anstey, Nicholas

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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