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

Abstract

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.

• Authors: Marius Keel, Luc Härter, Theresia Reding, Li-Kang Sun, Martin Hersberger, Burkhardt Seifert, Daniel Bimmler, Rolf Graf
• Journal: Critical care medicine (Crit Care Med) Vol. 37 Issue 5 Pg. 1642-8 (May 2009) ISSN: 1530-0293 [Electronic] United States
• PMID: 19325491 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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