Bv8 and endocrine gland-derived vascular endothelial growth factor stimulate hematopoiesis and hematopoietic cell mobilization
Bv8 and endocrine gland-derived vascular endothelial growth factor stimulate hematopoiesis and hematopoietic cell mobilization
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DOI：
10.1073/pnas.0407697101
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发表时间：
2004-11-30
影响因子：
11.1
通讯作者：
Ferrara, N
中科院分区：
文献类型：
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作者：
LeCouter, J;Zlot, C;Ferrara, N
Bv8 和内分泌腺源性 VEGF (EG-VEGF) 或前动力蛋白是两种高度相关的分泌蛋白，我们之前将其描述为选择性血管生成有丝分裂原。在这里，我们描述了 Bv8 在外周血细胞（特别是单核细胞、中性粒细胞和树突细胞）以及骨髓中的表达和功能特征。在人和小鼠中，这两种 Bv8 G 蛋白偶联受体在造血干细胞和特定成熟血细胞（包括淋巴细胞）中表达。 Bv8 在炎症部位的中性粒细胞中高度表达，并且可以以百日咳毒素敏感的方式刺激单核细胞迁移。 Bv8 或 EG-VEGF 具有相同的受体，可增加人类或小鼠造血干细胞培养物中粒细胞和单核细胞集落形成单位的数量。体内全身暴露于 Bv8 或 EG-VEGF 导致白细胞总数、中性粒细胞和单核细胞计数显着增加。此外，在 5-氟尿嘧啶损伤之前递送的腺病毒 (Av)Bv8 或 AvEG-VEGF 可促进造血细胞的存活并增强祖细胞的动员。总之，Bv8可以促进粒细胞和单核细胞谱系的存活和分化。 Bv8 可能通过自分泌或旁分泌信号机制来调节先天性和适应性免疫系统细胞的生长、存活和功能。
Bv8 and endocrine-gland-derived VEGF (EG-VEGF), or prokineticins, are two highly related, secreted proteins that we previously described as selective angiogenic mitogens. Here we describe the expression and functional characterization of Bv8 in peripheral blood cells, notably monocytes, neutrophils, and dendritic cells, and in the bone marrow. In human and mouse, the two Bv8 G protein-coupled receptors are expressed in hematopoietic stem cells and specific mature blood cells, including lymphocytes. Bv8 is highly expressed by neutrophils at sites of inflammation and can stimulate migration of monocytes, in a pertussis toxin-sensitive manner. Bv8, or EG-VEGF that shares the same receptors, increased numbers of colony-forming units granulocytic and monocytic in cultures of human or mouse hematopoietic stem cells. Systemic in vivo exposure to Bv8 or EG-VEGF resulted in significant increases in total leukocyte, neutrophil, and monocyte counts. Additionally, adenovirus (Av)Bv8 or AvEG-VEGF delivered just before 5-fluorouracil injury promoted the survival of hematopoietic cells and enhanced progenitor mobilization. In conclusion, Bv8 can promote survival and differentiation of the granulocytic and monocytic lineages. Bv8 potentially modulates growth, survival, and function of cells of the innate and adaptive immune systems, possibly through autocrine or paracrine signaling mechanisms.