Tryptase activates calcium-independent phospholipase A2 and releases PGE2 in airway epithelial cells.
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 A(2)gamma (iPLA(2)gamma) activity, resulting in increased arachidonic acid and PGE(2) release. These responses were inhibited by pretreating HSAEC with the iPLA(2)-selective inhibitor bromoenol lactone. The tryptase-stimulated PGE(2) 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 PGE(2) 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 iPLA(2)gamma-mediated phospholipid hydrolysis may prove beneficial in inflammatory airway diseases.
Rastogi
Prerna
P
Deptartment of Pathology, Saint Louis University School of Medicine, 1100 S. Grand Blvd., St. Louis, MO 63104, USA.
Young
Dawn M
DM
McHowat
Jane
J
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D054512:Phospholipases A2, Calcium-Independent / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis; D012137:Respiratory System / Q000166:cytology* / Q000201:enzymology; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D053802:Tryptases / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; C037913:CV 3988; D054512:Phospholipases A2, Calcium-Independent; D053802:Tryptases; D015232:Dinoprostone
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