Cell–Cell Interaction of Macrophages and Vascular Smooth MuscleCells in the Synthesis of Leukotriene B4

[摘要] Biosynthesis of LTB4during cell-cell interaction betweenvascular smooth muscle cells (SMC) and alveolar macrophages (AM) hasbeen investigated by use of both high-pressure Hquid chromatography(HPLC) and radtoimmunoassay (RIA). Both interleukin-β(IL-β) and tumour necrosis factor-α (TNFα) induceda time- and dose-dependent synthesis of 15-, and5-hydroxyeicosatetraenoic acids (HETEs) from cultured SMC. However,neither TNFα nor IL-1β induced a significantLTB4production in SMC alone or AM alone after 24 h ofincubation. Addition of IL-1β and TNFα simultaneously toSMC resulted in a dose-dependent synergistic increase of HETEs.Macrophages dose-dependently transformed extremely lowconcentrations of exogenous LTA4into LTB4.Incubation of vascular SMC with various numbers of AM in thepresence of IL-1β (5 units/ml) and TNFα (10units/ml) induced a great increase of LTB4synthesisin comparison with the detectable levels of LTB4producedby macrophages alone. Pretreatment of SMC with NDGA, cycloheximide,and actinomycin not only inhibited IL-1 and TNT induced HETEssynthesis but also abolished LTB4production whenco-incubated with macrophages. These results suggest thatLTB4in a mixture of SMC and macrophages could originatefrom a transcellular metabolism, i.e. macrophages transformingSMC-derived LTA4into LTB4.

[学科分类] 生理学与病理学