The airway epithelium and arachidonic acid 15-lipoxygenase

Pulmonary epithelial cells may be primarily responsible for initiating or regulating inflammatory responses in the airways, in part by releasing chemical mediators. Among the most potent mediators of inflammation are the lipoxygenase metabolites of arachidonic acid, including the leukotrienes and other mono and dihydroxyeicosatetraenoic acids (HETES). The human airway epithelium contains significant 15-lipoxygenase activity. Although some biologic functions of 15-lipoxygenase metabolites are known, further understanding of the role of this enzyme in the airway requires localization in tissue and studies of expression, regulation, and biologic activity. Towards these aims, we purified and characterized 15-lipoxygenase from eosinophil-enriched leukocytes. First, we studied cofactors that may be involved in regulating enzymatic activity. Second, we isolated to homogeneity, for the first time, human 15-lipoxygenase. This led to the determination of the N-terminal amino acid sequence and the discovery of homology among various mammalian lipoxygenases. Finally, we utilized this structural information to isolate a cDNA that encodes for human 15-lipoxygenase. The availability of a clone will permit studies of expression and the development of antibodies for tissue localization. Further research using molecular and antibody probes is expected to increase our understanding of the biologic roles of 15-lipoxygenase in airway epithelium.