Horigome K, Bullock E D, Johnson E M
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
J Biol Chem. 1994 Jan 28;269(4):2695-702.
Purified rat peritoneal mast cells in vitro die over a period of 2-6 days in conventional serum-containing medium. As mast cells die, they become pyknotic and undergo DNA fragmentation suggestive of an apoptotic process. Treatment of in vitro mast cells with nerve growth factor (NGF) greatly retards and reduces the death of mast cells (EC50 approximately 1 nM), with no effect on mast cell proliferation. Other neurotrophins have no such effect. NGF also induces the immediate early genes c-fos and NGFI-A with a similar dose dependence. In contrast to the secretagogue activity of NGF, neither the survival-promoting effect nor immediate early gene induction requires lysophosphatidylserine. The ability of NGF to promote mast cell survival is cell density-dependent and appears to be primarily because of induction of the synthesis and/or secretion of an autocrine survival factor by stimulated mast cells. These results suggest that the previously observed effects of NGF on mast cell numbers in vivo may in part be because of enhanced survival and that NGF may be an important mediator of mast cell function in normal and pathological states.
纯化的大鼠腹膜肥大细胞在含血清的常规培养基中于体外2至6天内死亡。随着肥大细胞死亡，它们会发生核固缩并经历DNA片段化，提示存在凋亡过程。用神经生长因子（NGF）处理体外肥大细胞可显著延缓并减少肥大细胞死亡（半数有效浓度约为1 nM），对肥大细胞增殖无影响。其他神经营养因子无此作用。NGF还以相似的剂量依赖性诱导即刻早期基因c-fos和NGFI-A。与NGF的促分泌活性不同，其促存活作用和即刻早期基因诱导均不依赖溶血磷脂酰丝氨酸。NGF促进肥大细胞存活的能力依赖细胞密度，且似乎主要是由于受刺激的肥大细胞诱导合成和/或分泌了一种自分泌存活因子。这些结果表明，先前观察到的NGF对体内肥大细胞数量的影响可能部分归因于存活率提高，并且NGF可能是正常和病理状态下肥大细胞功能的重要介质。
