Nerve growth factor functions as a chemoattractant for mast cells through both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways
Nerve growth factor functions as a chemoattractant for mast cells through both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways
复制标题
DOI：
10.1182/blood.v95.6.2052
复制
发表时间：
2000-03-15
期刊：
影响因子：
20.3
通讯作者：
Matsuda, H
中科院分区：
文献类型：
--
作者：
Sawada, J;Itakura, A;Matsuda, H
尽管是一种特征性的神经营养因子，但神经生长因子（NGF）影响肥大细胞的存活、分化和功能。我们研究了PI 3 K是否能诱导大鼠腹腔肥大细胞（PMCs）的定向迁移，NGF以剂量依赖的方式明显诱导PMCs的趋化运动，并引起F-actin的形态和分布的剧烈变化，这种变化可被肌动蛋白聚合抑制剂肉毒梭菌Ca毒素完全阻断，由于PMC组成性表达具有酪氨酸激酶结构域的NGF高亲和力受体（TrkA），我们专注于TrkA之后的信号级联中的下游效应物，NGF快速激活丝裂原活化蛋白激酶（MAPK）和磷脂酰肌醇3-激酶（PI 3 K），并且添加MAPK激酶和PI 3 K特异性抑制剂抑制细胞迁移和这些信号，在PMCs和成纤维细胞共培养体系中，PMCs向成纤维细胞定向迁移，抗NGF多克隆抗体的加入显著抑制了PMCs的迁移。这些结果表明，TrkA激活后，NGF通过MAPK和PI 3 K信号通路启动PMCs的趋化运动。因此，局部产生的神经生长因子可能在过敏性和非过敏性炎症条件下的肥大细胞积聚中起重要作用。(C)2000年，美国血液学会。
Despite being a well-characterized neurotrophic factor, nerve growth factor (NGF) influences survival, differentiation, and functions of mast cells. We investigated whether PI3K was able to induce directional migration of rat peritoneal mast cells (PMCs), NGF clearly induced chemotactic movement of PMCs in a dose-dependent manner with the drastic morphological change and distribution of F-actin, which was completely blocked by pretreatment with Clostridium botulinum Ca toxin, an actin-polymerization inhibitor, Because PMCs constitutively express the NGF high-affinity receptor (TrkA) with a tyrosine kinase domain, we focused on downstream effecters in signaling cascades following the TrkA, NGF rapidly activated both mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K), and the addition of inhibitors specific for MAPK kinase and PI3K suppressed cell migration and these signals, In the coculture system with PMCs and fibroblasts, which produce biologically active NGF, directional migration of PMCs to fibroblasts was observed, and the addition of anti-NGF polyclonal antibodies significantly suppressed the migration of PMCs, These findings suggested that NGF initiated chemotactic movement of PMCs through both MAPK and PI3K signaling pathways following TrkA activation. Thus, locally produced NGF may play an important role In mast cell accumulation in allergic and nonallergic inflammatory conditions. (C) 2000 by The American Society of Hematology.