Pancreatic stone protein is highly increased during posttraumatic sepsis and activates neutrophil granulocytes

Crit Care Med. 2009 May;37(5):1642-8. doi: 10.1097/CCM.0b013e31819da7d6.


Objectives: 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.

Patients: Eighty-three polytraumatic patients without pancreatic damage.

Measurements and main 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Chi-Square Distribution
  • Critical Care / methods
  • Critical Illness / mortality
  • Critical Illness / therapy
  • Female
  • Hospital Mortality / trends
  • Humans
  • Injury Severity Score
  • Intensive Care Units
  • L-Selectin / metabolism
  • Lithostathine / blood
  • Lithostathine / metabolism*
  • Male
  • Middle Aged
  • Multiple Trauma / complications*
  • Multiple Trauma / diagnosis
  • Neutrophil Infiltration / physiology*
  • Pancreas / metabolism*
  • Pancreas / physiopathology
  • Probability
  • Prognosis
  • Sensitivity and Specificity
  • Sepsis / blood*
  • Sepsis / etiology*
  • Sepsis / mortality
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Survival Analysis
  • Up-Regulation
  • Young Adult


  • Acute-Phase Proteins
  • Biomarkers
  • Lithostathine
  • L-Selectin
  • C-Reactive Protein