title: Increased plasma arginase activity in human sepsis: association with increased circulating neutrophils.
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.
authors.forename: Christabelle J
authors.initials: CJ
authors.lastname: Darcy
authors.forename: Tonia
authors.initials: T
authors.lastname: Woodberry
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Davis
authors.forename: Kim A
authors.initials: KA
authors.lastname: Piera
authors.forename: Yvette R
authors.initials: YR
authors.lastname: McNeil
authors.forename: Youwei
authors.initials: Y
authors.lastname: Chen
authors.forename: Tsin W
authors.initials: TW
authors.lastname: Yeo
authors.forename: J Brice
authors.initials: JB
authors.lastname: Weinberg
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood; D001119:Arginase / Q000097:blood* / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology* / Q000378:metabolism; D011874:Radiometry; D018805:Sepsis / Q000097:blood* / Q000201:enzymology*
chemical_list: D000596:Amino Acids; D001120:Arginine; D001119:Arginase