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Human Eosinophil Group IID Secretory Phospholipase A₂ Causes Surfactant Dysfunction^*

^* From the Sections on Pulmonary and Critical Care and Molecular Medicine, and Microbiology/Immunology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to: David A. Bass, MD, Dphil, FCCP, Internal Medicine-Pulmonary Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157; e-mail: dbass{at}wfubmc.edu

We have reported that secretory phospholipase A₂ (sPLA₂) enzymes are elevated in the BAL fluid of asthmatic patients following inhaled allergen challenges, but the sources and functional impact of the sPLA₂ enzymes are unknown. Eosinophils infiltrate lung mucosa during allergic asthma episodes, and eosinophils secrete inflammatory proteins, including sPLA₂. We and others have found that eosinophils contain 14-fold to 50-fold more sPLA₂ protein than neutrophils. We found that eosinophils secrete sPLA₂ in vitro rapidly (peak in 2 min), while neutrophil secretion of similar enzymatic activity is continuous for > 15 min. We have now specifically identified the group IID messenger RNA, isolated from peripheral blood eosinophils using reverse-transcriptase polymerase chain reaction.

The complementary DNA was sequenced and was confirmed as the group IID gene product. The preliminary real-time polymerase chain reaction data indicate that the IID sPLA₂ in eosinophils is increased by interleukin-5. In situ hybridization using the cloned complementary DNA showed that airway epithelial cells and infiltrating eosinophils (in nasal polyps) express the IID sPLA₂ messenger RNA.

Studies of surfactant function, by others and by us, have found that surfactant from the BAL fluid of challenged asthmatic patients is dysfunctional relative to surfactant from healthy control subjects or from asthmatic patients prior to allergen challenge. Recombinant group IID sPLA₂ caused surfactant dysfunction. The group IID has specificity for phosphatidylglycerol (PG) (rather than phosphatidylcholine). Although phosphatidylcholine is the predominant phospholipid in surfactant, the group IID sPLA₂ potently induced surfactant dysfunction in vitro, and that dysfunction paralleled hydrolysis of the PG component in the surfactant. Thus, eosinophils may contribute to surfactant dysfunction in asthma patients by causing hydrolysis of the PG component of the surfactant.

	Footnotes

 
Abbreviations: G = phosphatidylglycerol; sPLA₂ = secretory phospholipase A₂

This research was supported by National Institutes of Health grants NIH-HL50395, HL64226, and NC-ALA.

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