Splenocytes seed bone marrow of myeloablated mice: implication for atherosclerosis.

Splenocytes seed bone marrow of myeloablated mice: implication for atherosclerosis.
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DOI:
10.1371/journal.pone.0125961
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Sharifi BG
Sharifi BG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang L;Yang M;Arias A;Song L;Li F;Tian F;Qin M;Yukht A;Williamson IK;Shah PK;Sharifi BG

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髓外造血已被证明有助于包括心血管疾病在内的多种疾病的发病机制。在这个过程中,脾脏接种了动员的骨髓细胞,以增强其造血能力。目前还不清楚这些在脾脏中产生/重编程的移民细胞与骨髓中发现的移民细胞是否相似或不同。为了开始理解这一点,我们研究了成年脾细胞本身的相对效力,以重新填充致死性照射小鼠的骨髓及其在动脉粥样硬化中的功能后果。从GFP供体小鼠收获脾细胞,并移植到骨髓清除的野生型受体小鼠中,不包含任何骨髓辅助细胞。我们发现,成年脾细胞重新填充骨髓清除小鼠的骨髓和移植的细胞分化成一个完整的髓系细胞谱系的剧目。受体小鼠骨髓中单核细胞/巨噬细胞的水平取决于细胞来源,即,供体脾细胞产生的单核细胞/巨噬细胞明显多于供体骨髓细胞。尽管与供体骨髓细胞相比,供体脾细胞中存在的造血干细胞数量显著较低,但仍发生了这种情况。动脉粥样硬化研究表明,供体脾细胞显示出与供体骨髓细胞相似的致动脉粥样硬化和抗动脉粥样硬化活性水平。细胞培养研究表明,脾源性巨噬细胞的表型不同于骨髓源性巨噬细胞。总之,这些结果表明脾细胞可以接种骨髓清除小鼠的骨髓并调节动脉粥样硬化。此外,我们的研究显示了脾细胞在炎症性疾病治疗干预中的潜力。
Extramedullary hematopoiesis has been shown to contribute to the pathogenesis of a variety of diseases including cardiovascular diseases. In this process, the spleen is seeded with mobilized bone marrow cells that augment its hematopoietic ability. It is unclear whether these immigrant cells that are produced/reprogrammed in spleen are similar or different from those found in the bone marrow. To begin to understand this, we investigated the relative potency of adult splenocytes per se to repopulate bone marrow of lethally-irradiated mice and its functional consequences in atherosclerosis. The splenocytes were harvested from GFP donor mice and transplanted into myeloablated wild type recipient mice without the inclusion of any bone marrow helper cells. We found that adult splenocytes repopulated bone marrow of myeloablated mice and the transplanted cells differentiated into a full repertoire of myeloid cell lineages. The level of monocytes/macrophages in the bone marrow of recipient mice was dependent on the cell origin, i.e., the donor splenocytes gave rise to significantly more monocytes/macrophages than the donor bone marrow cells. This occurred despite a significantly lower number of hematopoietic stem cells being present in the donor splenocytes when compared with donor bone marrow cells. Atherosclerosis studies revealed that donor splenocytes displayed a similar level of atherogenic and atheroprotective activities to those of donor bone marrow cells. Cell culture studies showed that the phenotype of macrophages derived from spleen is different from those of bone marrow. Together, these results demonstrate that splenocytes can seed bone marrow of myeloablated mice and modulate atherosclerosis. In addition, our study shows the potential of splenocytes for therapeutic interventions in inflammatory disease.
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