Laegreid W W, Taylor S M, Silflow R M, Straub K M, Breeze R G, Liggitt H D, Leid R W
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040.
Inflammation. 1988 Oct;12(5):503-14. doi: 10.1007/BF00919442.
Lipoxygenase metabolites of arachidonic acid (AA), the leukotrienes (LTs), and hydroxyeicosatetraenoic acids (HETEs) are potent proinflammatory mediators. Release of LTs and HETEs by bovine alveolar macrophages (BAMs) was measured by reverse-phase high performance liquid chromatography. LTB4 (1.1 +/- 0.2 ng/10(6) cells) and 5-HETE (2.2 +/- 0.2 ng/10(6) cells) were the major metabolites calcium ionophore A23187-stimulated BAMs produced from endogenous AA. The tritiated forms of these compounds and their precursor fatty acids were produced following incorporation of [3H]AA into the cells and stimulation by calcium ionophore A23187. Incorporation of an alternative substrate, [3H]eicosapentaenoic acid [( 3H]EPA) into BAMs incubated in parallel resulted in production of [3H]LTB5 and [3H]5-hydroxyeicosapentaenoic acid (5-HEPE). Equivalent amounts of [3H]AA and [3H]EPA and of [3H]LTB4 and homologous [3H]LTB5 were released. BAM produced significantly greater amounts of [3H]5-HEPE than [3H]5-HETE, however. These findings indicate that the BAM 5-lipoxygenase is capable of metabolizing EPA to LTB5 and 5-HEPE, with the production of 5-HEPE preferred over 5-HETE.
花生四烯酸（AA）的脂氧合酶代谢产物，即白三烯（LTs）和羟基二十碳四烯酸（HETEs），是强效的促炎介质。通过反相高效液相色谱法测定了牛肺泡巨噬细胞（BAMs）释放的LTs和HETEs。LTB4（1.1±0.2 ng/10⁶个细胞）和5-HETE（2.2±0.2 ng/10⁶个细胞）是钙离子载体A23187刺激BAMs从内源性AA产生的主要代谢产物。在将[³H]AA掺入细胞并经钙离子载体A23187刺激后，产生了这些化合物及其前体脂肪酸的氚化形式。将替代底物[³H]二十碳五烯酸[（³H]EPA）掺入平行培养的BAMs中，导致产生[³H]LTB5和[³H]5-羟基二十碳五烯酸（5-HEPE）。释放的[³H]AA和[³H]EPA以及[³H]LTB4和同源的[³H]LTB5量相当。然而，BAM产生的[³H]5-HEPE量明显多于[³H]5-HETE。这些发现表明，BAM的5-脂氧合酶能够将EPA代谢为LTB5和5-HEPE，且优先产生5-HEPE而非5-HETE。
