Polymorphonuclear leukocyte dysregulation during the systemic inflammatory response syndrome

Area of Science:

• Immunology
• Cellular Biology
• Critical Care Medicine

Background:

• Systemic inflammatory response syndrome (SIRS) can lead to organ dysfunction.
• Altered polymorphonuclear leukocyte (PMN) function is a suspected contributor to SIRS-induced organ dysfunction.

Purpose of the Study:

• To investigate whole blood PMN function in patients with acute pancreatitis, a model for SIRS.
• To assess the impact of fibronectin and laminin adherence on PMN function in mild and severe pancreatitis.

Main Methods:

• Evaluated intracellular hydrogen peroxide (H2O2) production, CD32w/CD16 expression, and phagocytosis in whole blood PMNs.
• Compared PMN function in healthy controls, mild pancreatitis patients, and severe pancreatitis patients.
• Utilized dichlorofluorescein diacetate, fluorescently labeled antibodies, and fluorescent microspheres for assays.

Main Results:

• PMN adherence to fibronectin/laminin increased function by 5-20% in controls and mild pancreatitis, but 50-75% in severe pancreatitis.
• Pertussis toxin, pentoxifylline, and dibutyryl cAMP modulated PMN function differently across groups.
• Severe pancreatitis PMNs showed exaggerated oxidative responses to NaF, partially reduced by anti-interleukin-6.

Conclusions:

• Abnormal whole blood PMN function occurs during SIRS when adhering to fibronectin or laminin.
• This abnormality is partly mediated by a pertussis toxin-insensitive altered guanosine triphosphate-binding protein.
• Persistent PMN dysfunction correlates with multiple system organ failure in severe pancreatitis patients.