Rameshwar P, Poddar A, Gascón P
UMDNJ-New Jersey Medical School, Department of Medicine- Hematology, Newark, USA.
Leuk Lymphoma. 1997 Dec;28(1-2):1-10. doi: 10.3109/10428199709058325.
This review summarizes the current data regarding the mechanisms by which two mammalian neurokinins (tachykinins), substance P (SP) and neurokinin-A (NK-A) are involved in hematopoiesis. SP and NK-A are derived from the preprotachykinin-I (PPT-I) gene which can be induced by cytokines and neurotrophic factors. In the bone marrow (BM), nerve fibers and stroma are potential sources for the PPT-I gene products. SP and NK-A interact with either of three cloned receptors, neurokinin-1 (NK-1), NK-2 or NK-3, although SP and NK-A exhibit binding preferences for NK-1 and NK-2 respectively. Through specific receptors, SP and NK-A exert dichotomous hematopoietic effects mediated mostly by the BM stroma. SP enhances the proliferation of primitive BM stem cells and progenitors and these effects correlate with the induction of stimulatory hematopoietic growth factors. NK-A appears to be protective to stem cells through the induction of TGF-beta. Proliferation of myeloid progenitors is inhibited by NK-A, effects which correlate with the induction of two suppressive factors, TGF-beta and MIP-1alpha. Stimulation of NK-2 leads to partial blunting of the enhanced stimulatory effects mediated by NK-1. Furthermore, stimulatory hematopoietic cytokines upregulate NK-1 expression and downregulate the constitutively expressed NK-2 in BM stroma. Together, the experimental evidence suggests that NK-A-NK-2 interactions could be a feedback to hematopoietic stimulation. Expression of NK-1 and NK-2 in CD34+ cell lines and also, the presence of SP binding sites on primary CD34+ cells suggest that the neurokinins could be interacting directly with BM progenitors and stem cells. In BM stroma, cytokines and neurokinins regulate the expression of each other and also, their respective receptors. In summary, the current literature pertaining to hematopoietic regulation indicates the involvement of a complex network that includes, but not exclusive of the cytokines and neurokinins. The current models that pertain to stem cell proliferation and differentiation should therefore add neuropeptides to the list of hematopoietic modulators.
本综述总结了目前关于两种哺乳动物神经激肽（速激肽），即P物质（SP）和神经激肽A（NK-A）参与造血作用机制的相关数据。SP和NK-A源自前速激肽原-I（PPT-I）基因，该基因可被细胞因子和神经营养因子诱导。在骨髓（BM）中，神经纤维和基质是PPT-I基因产物的潜在来源。SP和NK-A与三种克隆受体之一，即神经激肽-1（NK-1）、NK-2或NK-3相互作用，尽管SP和NK-A分别对NK-1和NK-2表现出结合偏好。通过特定受体，SP和NK-A发挥二分造血作用，主要由BM基质介导。SP增强原始BM干细胞和祖细胞的增殖，这些作用与刺激性造血生长因子的诱导相关。NK-A似乎通过诱导转化生长因子-β（TGF-β）对干细胞起保护作用。NK-A抑制髓系祖细胞的增殖，其作用与两种抑制因子TGF-β和巨噬细胞炎症蛋白-1α（MIP-1α）的诱导相关。刺激NK-2会导致由NK-1介导的增强刺激作用部分减弱。此外，刺激性造血细胞因子上调NK-1表达并下调BM基质中组成性表达的NK-2。总之，实验证据表明NK-A-NK-2相互作用可能是对造血刺激的一种反馈。NK-1和NK-2在CD34+细胞系中的表达，以及原代CD34+细胞上SP结合位点的存在表明神经激肽可能直接与BM祖细胞和干细胞相互作用。在BM基质中，细胞因子和神经激肽相互调节彼此的表达以及它们各自受体的表达。总之，目前有关造血调节的文献表明涉及一个复杂的网络，其中包括但不限于细胞因子和神经激肽。因此，目前有关干细胞增殖和分化的模型应将神经肽添加到造血调节因子列表中。
