Rameshwar P, Ganea D, Gascón P
Department of Medicine, University of Medicine and Dentistry-New Jersey Medical School, Newark 07103.
Blood. 1993 Jan 15;81(2):391-8.
The neuropeptide Substance P (SP) is widely distributed in the peripheral nervous system. Its biologic effects have been extensively studied in the immune system. However, even though the bone marrow (BM) is innervated with SP-immunoreactive fibers and some of its cells not only express SP receptors (T and B cells, endothelial cells, and macrophages) but also produce SP (macrophages, eosinophils, and endothelial cells), the effects of SP on hematopoiesis are scanty. Furthermore, SP induces the production of hematopoietic growth factors (HGFs) (interleukin-1 [IL-1], IL-6, and tumor necrosis factor alpha) from human monocytes. In this study, we have found a potent in vitro stimulatory effect of SP (10(-8) to 10(-12) mol/L) on hematopoiesis for both erythroid and granulocytic progenitors in short-term methyl-cellulose BM cultures. SP alone, in the absence of exogenous HGFs, is able to sustain hematopoiesis in vitro. This stimulatory effect of SP is: (1) mostly mediated by the adherent cells; (2) completely abrogated by two SP receptor (SP-R) antagonists; and (3) partially reduced by anti-IL-1, IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Furthermore, it appears that the stimulatory effect of SP may be mediated by IL-3 and GM-CSF because we have also found that SP induces the release of these two cytokines from BM mononuclear cells. Considering that the SP effect occurs at concentrations as low as 10(-11) mol/L, and via a specific receptor, it appears that SP may play a physiologic role in regulating hematopoiesis, at least partially through the adherent BM cells and the release of HGFs, and may place SP, a neuropeptide, in a new category of hematopoietic regulators.
神经肽P物质（SP）广泛分布于外周神经系统。其生物学效应已在免疫系统中得到广泛研究。然而，尽管骨髓（BM）有SP免疫反应性纤维支配，且其一些细胞不仅表达SP受体（T细胞、B细胞、内皮细胞和巨噬细胞），还产生SP（巨噬细胞、嗜酸性粒细胞和内皮细胞），但SP对造血作用的研究却很少。此外，SP可诱导人单核细胞产生造血生长因子（HGFs）（白细胞介素-1 [IL-1]、IL-6和肿瘤坏死因子α）。在本研究中，我们发现在短期甲基纤维素BM培养中，SP（10⁻⁸至10⁻¹²mol/L）对红系和粒系祖细胞的造血具有强大的体外刺激作用。单独的SP在无外源性HGFs的情况下能够在体外维持造血。SP的这种刺激作用：（1）主要由贴壁细胞介导；（2）被两种SP受体（SP-R）拮抗剂完全消除；（3）被抗IL-1、IL-3、IL-6和粒细胞-巨噬细胞集落刺激因子（GM-CSF）部分减弱。此外，似乎SP的刺激作用可能由IL-3和GM-CSF介导，因为我们还发现SP可诱导BM单核细胞释放这两种细胞因子。鉴于SP在低至10⁻¹¹mol/L的浓度下就能发挥作用，且通过特定受体起作用，似乎SP可能在调节造血中发挥生理作用，至少部分是通过BM贴壁细胞和HGFs的释放，这可能使神经肽SP成为一类新的造血调节因子。
