An elevated number of eosinophils is a frequent finding in allergy and asthma. Arachidonic acid metabolites produced by the eosinophil are capable of causing airway inflammation, mucus secretion, and bronchoconstriction. The products of the 15- lipoxygenase pathway are the major metabolites of arachidonic acid in human eosinophils. The purpose of this project is to characterize the 15-lipoxygenase from human eosinophils. I have recently purified, for the first time, human 15-lipoxygenase to homogeneity. These purification procedures will make the proposed research possible. There are several reasons to purify the 15-lipoxygenase enzyme. First, this will allow kinetic characterization of the enzyme and give insight into regulation of lipoxygenation. Second, purified enzyme will permit the determination of the amino acid sequence of the protein which will aid in relating the enzyme's structure to its function. Third, protein purification permits cloning of the enzyme to make it more available for further studies. Finally, the development of specific antibodies will enable histochemical studies to be performed to more precisely localize the enzyme. These studies should lead to a greater understanding of the regulation of arachidonic acid metabolism and should contribute to defining the role of the eosinophil in allergy and asthma. Ultimately, this may provide the basis for new therapeutic alternatives.
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