Leukotriene Synthesis by Epithelial Cells of Human Mucosa-Associated Lymphoid Tissue

Abstract

Lymphocyte activation and immunoglobulin synthesis are key events in acquired immunity. Leukotrienes are lipid mediators known to modulate these events in vitro, but how they might directly interact with lymphocytes in vivo has been unclear. The enzyme 5-lipoxygenase catalyzes the rate-limiting steps in leukotriene synthesis. Here we report that 5-lipoxygenase protein was found in abundance in epithelial cells of human mucosa-associated lymphoid tissue. In addition, leukotriene A4 hydrolase and the 5-lipoxygenase activating protein were also present in lymphoid tissue epithelium, indicating that these cells should be able to independently metabolize arachidonic acid to leukotrienes. Indeed, epithelium-rich tissue fractions were capable of synthesizing both leukotriene B4 and 5-hydroxyeicosatetraenoic acid from arachidonic acid. The abundance of 5-lipoxygenase protein, the amount of leukotriene B4 secreted, and the extent of epithelium stratification differed between samples from different donors. Together, these results place leukotriene synthesis in an unexpected site, mucosa-associated lymphoid tissue epithelium, where secreted leukotrienes may affect lymphocyte activation and immunoglobulin synthesis. Dysregulation of leukotriene synthesis in this context, in turn, may be relevant to asthma, allergic response, and autoimmune disorders. Abbreviations: AA, arachidonic acid; DAB, 3,3'diaminobenzidine; FLAP, 5-lipoxygenase activating protein; HETE, hydroxyeicosatetraenoic acid; Ig, immunoglobulin; 5-LO, 5-lipoxygenase; LT, leukotriene; MALT, mucosaassociated lymphoid tissue; RBL, rat basophilic leukemia.