LEUKOTRIENE B-4 FORMATION - HUMAN NEUTROPHIL AIRWAY EPITHELIAL-CELL INTERACTIONS

Leukotriene B-4 (LTB(4)) is a potent inflammatory mediator involved in the pathogenesis of many pulmonary diseases. Although the neutrophil is the predominant source of LTB(4), other cells can also interact with neutrophils and increase LTB(4) formation. In this study, we investigated whether human neutrophil-airway epithelial cell interactions can increase LTB(4) formation. Neutrophils were cocultured with transformed airway epithelial cells (9HTEo(-) cells), and LTB(4) and leukotriene A(4) (LTA(4)) degradation product release was measured by high-performance liquid chromatography and ultraviolet spectrometry. When stimulated with the calcium ionophore A-23187, neutrophil-9HTEo(-) cell cocultures released more LTB(4) and less LTA(4) degradation products in a time- and dose-related manner than did neutrophils alone. This increase in LTB(4) release involved the metabolism of neutrophil-derived LTA(4) to LTB(4) by 9HTEo(-) cells and was affected by the neutrophil-to-epithelial cell ratio. Enhanced LTB(4) release required proximity between neutrophils and 9HTEo(-) cells but not specific cell-cell adhesion. Our data demonstrate that human neutrophil-airway epithelial cell interactions can increase LTB(4) formation through transcellular arachidonic acid metabolism.