Elevated cytosolic phospholipase A₂ expression and activity in human neutrophils during sepsis

Sepsis is defined as the systemic inflammatory response to infection. Phospholipase A₂ (PLA₂) plays an important role in inflammation processes by initiating the production of inflammatory mediators. The role of cytosolic PLA (cPLA₂) has not yet been identified in inflammatory and infectious disease clinical settings. The aim of the present research was to determine whether cPLA₂ activity has a role during sepsis. Since neutrophil activation has been documented during sepsis, these cells were chosen as a model to evaluate the function of cPLA₂ in this clinical setting. cPLA₂ was studied at 3 levels: activity, protein expression, and messenger RNA (mRNA). Neutrophils from 32 septic patients with and without bacteremia were examined, cPLA₂ activity was measured using labeled phosphatidyl choline vesicles as a substrate, and total PLA₂ was determined by the release of labeled arachidonic acid from prelabeled cells. A significant increase in cPLA₂ activity, protein expression, and total PLA₂ activity in neutrophils was detected during sepsis, mRNA levels, detected by reverse transcriptase- polymerase chain reaction, were significantly higher during sepsis, indicating that the increase in the amount of cPLA₂ is regulated on the mRNA level. The significant elevation of cPLA₂ activity and expression in neutrophils during sepsis suggests that this enzyme plays a major role in neutrophil function in this clinical setting.