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Am J Physiol Lung Cell Mol Physiol 295: L925-L932, 2008. First published September 12, 2008; doi:10.1152/ajplung.90230.2008
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Tryptase activates calcium-independent phospholipase A2 and releases PGE2 in airway epithelial cells

Prerna Rastogi, Dawn M. Young, and Jane McHowat

Department of Pathology, Saint Louis University School of Medicine, St. Louis, Missouri

Submitted 14 March 2008 ; accepted in final form 10 September 2008

Human small airway epithelial cells (HSAEC) form the boundary between the external environmental allergens and the internal lung milieu. Mast cells are present in human lung tissue interspersed within the pulmonary epithelium and can secrete a host of pre- and newly formed mediators from their granules, which may propagate small airway inflammation. In this study, tryptase stimulation of HSAEC increased membrane-associated, calcium-independent phospholipase A2{gamma} (iPLA2{gamma}) activity, resulting in increased arachidonic acid and PGE2 release. These responses were inhibited by pretreating HSAEC with the iPLA2-selective inhibitor bromoenol lactone. The tryptase-stimulated PGE2 production was inhibited by treating HSAEC with the cyclooxygenase (COX)-1-selective inhibitor SC-560 and the nonselective COX inhibitor aspirin but not by the COX-2-selective inhibitor CAY10404, indicating that the early release of arachidonic acid is metabolized by constitutive COX-1 to form PGE2 in tryptase-stimulated HSAEC. Additionally, platelet-activating factor production and neutrophil adherence to tryptase-stimulated HSAEC was also increased. This complex response can set up a cascade of inflammatory mediator production in small airways. We speculate that selective inhibition of iPLA2{gamma}-mediated phospholipid hydrolysis may prove beneficial in inflammatory airway diseases.

prostaglandin E2; arachidonic acid; bromoenol lactone


Address for reprint requests and other correspondence: J. McHowat, Dept. of Pathology, Saint Louis Univ. School of Medicine, Doisy Research Bldg., 3rd Floor, 1100 S. Grand Blvd., St. Louis, MO 63104 (e-mail: jane.mchowat{at}tenethealth.com)






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