Yamasu K, Onoe H, Soma G, Oshima H, Mizuno D
Biotechnology Research Center, Teikyo University, Kanagawa, Japan.
J Biol Response Mod. 1989 Dec;8(6):644-55.
Inflammation plays an important role in homeostasis of the body. We therefore can assume that an inflammatory state occurs during ontogenesis of animals. To address this problem, we examined the ability of tumor necrosis factor (TNF), one of the inflammatory mediators, to be secreted by mouse cells during development. We cultured cells prepared from various parts of fetuses (10-19 days of gestation) and postnatal brains by collagenase digestion and assayed the secreted TNF activity by the L-929 cytotoxicity test. We found TNF activity by fetal cells without any stimulation. The spontaneous secretion of TNF was relatively high at around 13-15 days of gestation. The secretion was enhanced by lipopolysaccharide (LPS), showing that fetal cells are in an activated state for TNF secretion. These TNF activities were neutralized completely by rabbit anti-murine TNF antibody. Spontaneous and LPS-enhanced secretion by postnatal brain cells reached a peak around 7 days after birth, and thereafter declined rapidly. This time course was well correlated to the increase in the weight of brain. The producing cells were negative in macrophage marker surface antigen, and heterogeneous in relation to adherence and phagocytic activity, showing that TNF is secreted by various types of cells in the fetal body. These results suggest the presence of an inflammation-like state during ontogenesis. We consider that this "ontogenic inflammation" may be the prototype of inflammation, which can regulate homeostasis of the adult body.
炎症在机体的稳态中发挥着重要作用。因此，我们可以假定在动物个体发育过程中会出现炎症状态。为解决这一问题，我们检测了炎症介质之一肿瘤坏死因子（TNF）在小鼠发育过程中由细胞分泌的能力。我们通过胶原酶消化培养了从胎儿（妊娠10 - 19天）和出生后小鼠大脑不同部位制备的细胞，并通过L - 929细胞毒性试验检测分泌的TNF活性。我们发现未经任何刺激的胎儿细胞具有TNF活性。在妊娠13 - 15天左右，TNF的自发分泌相对较高。脂多糖（LPS）可增强其分泌，表明胎儿细胞处于TNF分泌的激活状态。这些TNF活性可被兔抗鼠TNF抗体完全中和。出生后大脑细胞的自发分泌和LPS增强分泌在出生后约7天达到峰值，此后迅速下降。这一动态过程与大脑重量的增加密切相关。产生细胞的巨噬细胞标志物表面抗原呈阴性，在贴壁和吞噬活性方面具有异质性，表明TNF由胎儿体内的多种细胞分泌。这些结果提示在个体发育过程中存在类似炎症的状态。我们认为这种“个体发育性炎症”可能是炎症的原型，它可以调节成体机体的稳态。
