Endothelial cells are a critical component of the bone marrow (BM) stromal network, which maintains and regulates hematopoietic cells. Vascular regeneration precedes, and is necessary for, successful hematopoietic stem cell (HSC) transplantation, the only cure for most hematopoietic diseases. Recent data suggest that mature hematopoietic cells regulate BM stromal-cell function. Whether a similar cross-talk regulates the BM vasculature is not known. Here we found that donor hematopoietic cells act on sinusoidal endothelial cells and induce host blood vessel and hematopoietic regeneration after BM transplantation in mice. Adoptive transfer of BM, but not peripheral, granulocytes prevented the death of mice transplanted with limited numbers of HSCs and accelerated recovery of host vessels and hematopoietic cells. Moreover, selective granulocyte ablation in vivo impaired vascular and hematopoietic regeneration after BM transplantation. Gene expression analyses indicated that granulocytes are the main source of the cytokine TNFα, whereas its receptor TNFR1 is selectively upregulated in regenerating blood vessels. In adoptive transfer experiments, wild type, but not Tnfa^-/-, granulocytes induced vascular recovery, and wild-type granulocyte transfer did not prevent death or promote vascular regeneration in Tnfr1^-/-; Tnfr2^-/- mice. Thus, by delivering TNFα to endothelial cells, granulocytes promote blood vessel growth and hematopoietic regeneration. Manipulation of the cross-talk between granulocytes and endothelial cells may lead to new therapeutic approaches to improve blood vessel regeneration and increase survival and hematopoietic recovery after HSC transplantation.

中文翻译：

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粒细胞源性TNFα促进骨髓中血管和造血的再生。

内皮细胞是维持和调节造血细胞的骨髓基质网络的关键组成部分。血管再生是成功进行造血干细胞（HSC）移植的先决条件，也是成功移植的必要条件，而造血干细胞是大多数造血疾病的唯一治疗方法。最近的数据表明，成熟的造血细胞调节BM基质细胞功能。尚不清楚类似的串扰是否能调节BM脉管系统。在这里，我们发现供体造血细胞作用于正弦血管内皮细胞，并诱导小鼠骨髓移植后诱导宿主血管和造血细胞再生。BM而不是外周粒细胞的过继转移阻止了移植了有限数量的HSC的小鼠的死亡，并加速了宿主血管和造血细胞的恢复。而且，体内选择性粒细胞消融破坏了BM移植后血管和造血的再生。基因表达分析表明，粒细胞是细胞因子TNFα的主要来源，而其受体TNFR1在再生血管中选择性上调。在过继转移实验中，是野生型，但不是Tnfa^-/-，粒细胞诱导血管恢复，而野生型粒细胞转移不能预防Tnfr1 ^-/-的死亡或促进血管再生。Tnfr2 ^-/-小鼠。因此，通过将TNFα递送至内皮细胞，粒细胞促进血管生长和造血再生。粒细胞和内皮细胞之间的串扰的操纵可能会导致新的治疗方法，以改善HSC移植后的血管再生和增加生存率和造血恢复。