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 wit h neutrophils and increase LTB(4) formation. In this study, we investi gated whether human neutrophil-airway epithelial cell interactions can increase LTB(4) formation. Neutrophils were cocultured with transform ed airway epithelial cells (9HTEo(-) cells), and LTB(4) and leukotrien e A(4) (LTA(4)) degradation product release was measured by high-perfo rmance liquid chromatography and ultraviolet spectrometry. When stimul ated with the calcium ionophore A-23187, neutrophil-9HTEo(-) cell cocu ltures released more LTB(4) and less LTA(4) degradation products in a time- and dose-related manner than did neutrophils alone. This increas e 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-e pithelial cell ratio. Enhanced LTB(4) release required proximity betwe en neutrophils and 9HTEo(-) cells but not specific cell-cell adhesion. Our data demonstrate that human neutrophil-airway epithelial cell int eractions can increase LTB(4) formation through transcellular arachido nic acid metabolism.