Humes J L, Opas E E, Galavage M, Soderman D, Bonney R J
Biochem J. 1986 Jan 1;233(1):199-206. doi: 10.1042/bj2330199.
Resident mouse peritoneal macrophages when exposed to zymosan during the first day of cell culture synthesize and secrete large amounts of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4), the respective products of cyclo-oxygenase- and 5-lipoxygenase-catalysed oxygenations of arachidonic acid. Under these conditions of cell stimulation only small amounts of hydroxyeicosatetraenoic acids (HETEs) are concomitantly produced. However, exogenously added arachidonic acid is metabolized to large amounts of 12- and 15-HETE and only relatively small amounts of PGE2. No LTC4 is formed under these conditions. In contrast, resident mouse peritoneal macrophages in cell culture for 4 days synthesized less PGE2 and LTC4 when exposed to zymosan. However, these macrophage populations continue to synthesize 12-HETE from exogenously added arachidonic acid. Zymosan induced the secretion of a lysosomal enzyme, N-acetyl-beta-glucosaminidase, equally in both 1- and 4-day cultures. Both 12- and 15-hydroperoxyeicosatetraenoic acids (HPETEs), the precursors of 12- and 15-HETE, were found to be irreversible inhibitors of the cyclo-oxygenase pathway and reversible inhibitors of the 5-lipoxygenase pathway in macrophages. 15-HETE were found to be reversible inhibitors of both pathways. Thus the oxidation of arachidonic oxidation of arachidonic acid to both prostaglandins and leukotrienes may be under intracellular regulation by products of 12- and 15-lipoxygenases.
在细胞培养的第一天，将小鼠腹腔巨噬细胞暴露于酵母聚糖时，它们会合成并分泌大量的前列腺素E2（PGE2）和白三烯C4（LTC4），这两种物质分别是环氧化酶和5-脂氧合酶催化花生四烯酸氧化的产物。在这些细胞刺激条件下，仅会同时产生少量的羟基二十碳四烯酸（HETEs）。然而，外源性添加的花生四烯酸会代谢生成大量的12-和15-HETE，而仅生成相对少量的PGE2。在这些条件下不会形成LTC4。相比之下，在细胞培养4天的小鼠腹腔巨噬细胞暴露于酵母聚糖时，合成的PGE2和LTC4较少。然而，这些巨噬细胞群体继续从外源性添加的花生四烯酸中合成12-HETE。酵母聚糖在1天和4天的培养物中均能同等程度地诱导溶酶体酶N-乙酰-β-氨基葡萄糖苷酶的分泌。12-和15-氢过氧二十碳四烯酸（HPETEs），即12-和15-HETE的前体，被发现是巨噬细胞中环氧化酶途径的不可逆抑制剂和5-脂氧合酶途径的可逆抑制剂。15-HETE被发现是这两条途径的可逆抑制剂。因此，花生四烯酸氧化为前列腺素和白三烯的过程可能受到12-和15-脂氧合酶产物的细胞内调节。
