Dorsch Marion, Qiu Yubin, Soler Dulce, Frank Nita, Duong Thao, Goodearl Andrew, O'Neil Steve, Lora Jose, Fraser Christopher C
Millennium Pharmaceuticals Inc., 35 Landsdowne St., Cambridge, MA 02139, USA.
J Leukoc Biol. 2005 Aug;78(2):426-34. doi: 10.1189/jlb.0205061. Epub 2005 May 20.
Macrophages exist as sentinels in innate immune response and react by expressing proinflammatory cytokines and up-regulating antigen-presenting and costimulatory molecules. We report a novel function for prokineticin-1 (PK1)/endocrine gland-derived vascular endothelial growth factor. Screening of murine tissue sections and cells for specific binding site leads to the identification of macrophages as an in vivo cellular target for PK1. We demonstrate PK1 induces differentiation of murine and human bone marrow cells into the monocyte/macrophage lineage. Human peripheral blood monocytes respond to PK1 by morphological changes and down-regulation of B7-1, CD14, CC chemokine receptor 5, and CXC chemokine receptor 4. Monocytes treated with PK1 have elevated interleukin (IL)-12 and tumor necrosis factor alpha and down-regulated IL-10 production in response to lipopolysaccharide. PK1 induces a distinct monocyte-derived cell population, which is primed for release of proinflammatory cytokines that favor a T helper cell type 1 response.
巨噬细胞作为先天性免疫反应的哨兵存在，并通过表达促炎细胞因子和上调抗原呈递及共刺激分子做出反应。我们报告了促动力蛋白-1（PK1）/内分泌腺源性血管内皮生长因子的一种新功能。对小鼠组织切片和细胞进行特异性结合位点筛选，结果鉴定出巨噬细胞是PK1在体内的细胞靶点。我们证明PK1可诱导小鼠和人类骨髓细胞分化为单核细胞/巨噬细胞谱系。人外周血单核细胞对PK1的反应是形态改变以及B7-1、CD14、CC趋化因子受体5和CXC趋化因子受体4的下调。用PK1处理的单核细胞在对脂多糖的反应中，白细胞介素（IL）-12和肿瘤坏死因子α升高，而IL-10产生下调。PK1诱导产生一种独特的单核细胞衍生细胞群体，该群体准备释放有利于1型辅助性T细胞反应的促炎细胞因子。
