Murakami M, Kudo I, Suwa Y, Inoue K
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Eur J Biochem. 1992 Oct 1;209(1):257-65. doi: 10.1111/j.1432-1033.1992.tb17284.x.
Group II phospholipase A2 was detected in appreciable amounts in rat peritoneal mast cells. The effect of several inhibitors specific to 14-kDa group-II phospholipase A2, including two proteinaceous inhibitors and a product of microorganisms with a low molecular mass, on mast-cell activation was examined. When rat peritoneal mast cells were sensitized with IgE and then challenged with antigen, the specific phospholipase-A2 inhibitors suppressed histamine release in a concentration-dependent manner. By contrast, these inhibitors showed no effect on prostaglandin generation under the same conditions. Histamine release from rat peritoneal mast cells subjected to non-immunochemical stimuli, such as concanavalin A, the Ca2+ ionophore A23187, compound 48/80 and substance P was also suppressed. When rat peritoneal mast cells were treated with 14-kDa-group-II-phospholipase-A2-specific inhibitors, washed and stimulated, histamine release was not affected appreciably. Similar suppressive effects of the inhibitors on histamine release were observed with mouse cultured bone-marrow-derived mast cells. When bone-marrow-derived mast cells were activated, they secreted both a soluble and an ecto-enzyme form of 14-kDa group-II phospholipase A2, although appearance of the enzyme associated with the external surface of cells was observed transiently. An appreciable amount of membrane phospholipids was degraded during activation of mast cells, which was decreased by treatment with 14-kDa-group-II-phospholipase-A2 inhibitor. These observations suggest that degranulation and eicosanoid generation in mast cells are regulated independently by discrete phospholipases A2 and that the 14-kDa group-II phospholipase A2 released from mast cells during activation may play an essential role in the progression of the degranulation process.
在大鼠腹膜肥大细胞中检测到了大量的II型磷脂酶A2。研究了几种对14 kDa II型磷脂酶A2具有特异性的抑制剂，包括两种蛋白质类抑制剂和一种低分子量微生物产物，对肥大细胞激活的影响。当用IgE致敏大鼠腹膜肥大细胞，然后用抗原进行攻击时，特异性磷脂酶A2抑制剂以浓度依赖的方式抑制组胺释放。相比之下，在相同条件下，这些抑制剂对前列腺素的生成没有影响。来自大鼠腹膜肥大细胞的组胺释放，在受到非免疫化学刺激，如伴刀豆球蛋白A、Ca2+离子载体A23187、化合物48/80和P物质时，也受到抑制。当用14 kDa II型磷脂酶A2特异性抑制剂处理大鼠腹膜肥大细胞，洗涤并刺激后，组胺释放没有明显受到影响。在小鼠培养的骨髓来源肥大细胞中也观察到了抑制剂对组胺释放的类似抑制作用。当骨髓来源的肥大细胞被激活时，它们分泌出可溶性和胞外酶形式的14 kDa II型磷脂酶A2，尽管与细胞外表面相关的酶的出现是短暂的。在肥大细胞激活过程中，有相当数量的膜磷脂被降解，而用14 kDa II型磷脂酶A2抑制剂处理后这种降解减少。这些观察结果表明，肥大细胞中的脱颗粒和类花生酸生成是由离散的磷脂酶A2独立调节的，并且激活过程中从肥大细胞释放的14 kDa II型磷脂酶A2可能在脱颗粒过程的进展中起重要作用。
