title: Pancreatic stone protein is highly increased during posttraumatic sepsis and activates neutrophil granulocytes.
abstract: OBJECTIVE
  The level of pancreatic stone protein/regenerating protein (PSP/reg), a secretory protein produced in the pancreas, increases dramatically during pancreatic disease. However, after stress (e.g., anesthesia), PSP/reg levels are increased transiently in animals without pancreatic injury. Therefore, we aimed to determine whether PSP/reg is an acute-phase protein after nonpancreatic trauma.
  
  
  METHODS
  Eighty-three polytraumatic patients without pancreatic damage.
  
  
  RESULTS
  We compared serum PSP/reg levels from polytraumatic patients without pancreatic damage with those in healthy controls (n = 38). C-reactive protein, interleukin-6, procalcitonin, and leukocyte numbers were also compared. The expression of CD62L and CD11b on neutrophils after exposure to PSP/reg was analyzed by flow cytometry. Thirty-three patients (39%) developed sepsis, 32 (38%) had local infections, and 18 (21%) had no infections. At admission, PSP/reg serum levels (10.2 [6.2-14.5] ng/mL; median [interquartile range]) were comparable with those in healthy controls (10.4 [7.5-12.3] ng/mL). During hospital stay, PSP/reg levels were elevated significantly in patients with sepsis (146.4 ng/mL) and in patients with infections (111.4 ng/mL) compared with patients without infections (22.8 ng/mL). Furthermore, binding of fluorescein isothiocyanate-labeled recombinant PSP/reg to human neutrophils was demonstrated. Recombinant PSP/reg elicited a dose-dependent shedding of L-selectin (CD62L) and upregulation of beta2-integrin (CD11b) in neutrophils, which indicates that PSP/reg activates neutrophils.
  
  
  CONCLUSIONS
  We conclude that PSP/reg is up-regulated in blood after trauma, and the PSP/reg level is related to the severity of inflammation. Furthermore, PSP/reg binds to and activates neutrophils. Therefore, PSP/reg might be an acute-phase protein that could serve as a marker for posttraumatic complications.
authors.affiliation: Departments of Trauma Surgery, University Hospital Zürich, Zurich, Switzerland.
authors.forename: Marius
authors.initials: M
authors.lastname: Keel
authors.forename: Luc
authors.initials: L
authors.lastname: Härter
authors.forename: Theresia
authors.initials: T
authors.lastname: Reding
authors.forename: Li-Kang
authors.initials: LK
authors.lastname: Sun
authors.forename: Martin
authors.initials: M
authors.lastname: Hersberger
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Seifert
authors.forename: Daniel
authors.initials: D
authors.lastname: Bimmler
authors.forename: Rolf
authors.initials: R
authors.lastname: Graf