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Garret Zallen, MD; Ernest E. Moore, MD; Jeffrey L. Johnson, MD; Douglas Y. Tamura, MD; Michael Barkin; Hubertus Stockinger, PhD; Christopher C. Silliman, MD, PhD

Arch Surg. 1998;133:1229-1233.

Background  Secretory phospholipase A₂ (sPLA₂) is a potent proinflammatory enzyme that stimulates inflammation through the production of reactive lipids. However, enzymatic inhibitors have been disappointing in their effectiveness in halting hyperinflammation.

Objective  To determine whether sPLA₂ acts directly on neutrophil plasma membrane lipids or via a nonenzymatic mechanism.

Design  Isolated neutrophils (PMNs) were incubated with 3 types of sPLA₂, and elastase and superoxide release from PMNs was measured. Ethyleneglycotetraacetic acid was used as a selective enzymatic inhibitor. The PMNs were exposed to sPLA₂ in the presence and absence of ethyleneglycotetraacetic acid and the release of elastase was measured.

Setting  Urban trauma research laboratory.

Patients  Normal healthy donors of PMNs.

Main Outcome Measures  Stimulated release of superoxide and elastase.

Results  The sPLA₂ acted directly on plasma membrane lipids to stimulate the PMN to produce superoxide and release elastase. This mechanism is blocked with enzymatic inhibition of sPLA₂. The sPLA₂ also provokes elastase release from PMNs independently of its enzymatic function. This mechanism is not blocked with traditional enzymatic inhibitors.

Conclusions  These data indicate that the sPLA₂ can act directly on PMNs to stimulate the release of inflammatory mediators via enzymatic degradation of plasma membrane lipids. In addition, sPLA₂ can act as a ligand and stimulate the PMN independently of its enzymatic activity.

From the Department of Surgery, Denver Health Medical Center, Denver, Colo (Drs Zallen, Moore, Johnson, and Tamura and Mr Barkin); Department of Biochemicals, Boehringer Mannheim GmbH, Penzberg, Germany (Dr Stockinger); and Department of Pediatrics, University of Colorado, Denver (Dr Silliman).

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