Role of 5-lipoxygenase and its production of leukotriene B_4 in innate host defense and diseases

摘要

5-Lipoxygenase (5-LO) is an important enzyme that dominates the metabolism of arachidonic acid and the synthesis of leukotrienes, of which leukotriene B_4 (LTB_4) is suggested to be one of the most potent chemoattractants and activators of leukocytes. 5-LO is normally limited to hematopoetic cells, e.g. granulocytes and macrophages, where LTB_4 is produced. Leukotrienes play an important role in the innate defense system, in the antimicrobial defense system, and in intercellular signaling. Under pathophysiological conditions, overproduction of LTB_4 was noted in multiple cells. It is known that 5-LO and its production of LTB_4 are involved in the maintenance of normal host defense, initiation of inflammation, migration of leukocytes, development of endothelial barrier dysfunction, hyperresponsiveness of smooth muscle cells, stimulation of mucus secretion, reduction of mucociliary clearance, and tissue remodeling. In order to understand the role of 5-LO and its production in functions of the innate host defense, this review will focus on the location and metabolism of 5-LO, its distribution and function within the leukocyte system, including neutrophils, monocytes, and macrophages, and overactivation of 5-LO in the development of chronic obstructive pulmonary disease.