A role for leptin in sustaining lymphopoiesis and myelopoiesis
A role for leptin in sustaining lymphopoiesis and myelopoiesis
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DOI：
10.1073/pnas.0712053105
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发表时间：
2008-02-12
影响因子：
11.1
通讯作者：
Fraker, Pamela J.
中科院分区：
文献类型：
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作者：
Claycombe, Kate;King, Louis E.;Fraker, Pamela J.
尽管瘦素以其调节食物摄入而闻名，但它在免疫功能中具有许多新兴的作用。为了更好地确定瘦素在造血过程中的作用，比较瘦素缺陷型肥胖小鼠（ob/ob）和C57 BL/6瘦型野生型对照。尽管它们体型庞大，消耗了大量的营养物质，但ob/ob小鼠骨髓中的有核细胞只有对照组的60%。瘦素缺乏对B细胞区室的影响最大，其细胞减少70%，使前B细胞和未成熟8细胞的绝对数量分别减少至正常的21%和12%，并表明ob/ob小鼠中淋巴细胞生成显著减少。虽然在肥胖小鼠中骨髓细胞的比例几乎保持正常，但它们的粒细胞和单核细胞的绝对数量也分别减少了40%和25%。提供重组瘦素7天后，大量淋巴细胞生成得到促进，肥胖小鼠骨髓中的B细胞数量增加了两倍，而前B细胞和未成熟B细胞的数量分别增加了一倍和两倍。12天的补充使这些亚群接近正常比例。瘦素治疗还促进骨髓生成，使得肥胖小鼠的骨髓在7天后含有正常数量的单核细胞和粒细胞。两者合计，数据支持瘦素在维持淋巴细胞生成和骨髓细胞生成中的重要作用。
Although leptin is known for its regulation of food intake, it has many emerging roles in immune function. To better define the role of leptin in hematopoietic processes, a leptin-deficient obese mouse (ob/ob) and C57BL/6 lean wild-type controls were compared. Despite their large size and consumption of substantial amounts of nutrients, the ob/ob mice had only 60% as many nucleated cells in their marrow as controls. The greatest impact of leptin deficiency was on the B cell compartment that had 70% fewer cells, reducing the absolute number of pre-B and immature 8 cells to 21% and 12% of normal, respectively, and indicating a significant reduction in lymphopoiesis in ob/ob mice. Whereas the proportion of myeloids remained nearly normal in the obese mice, they also exhibited a reduction of 40% and 25%, respectively, in absolute numbers of granulocytes and monocytes. Seven days of provision of recombinant leptin promoted substantial lymphopoiesis, increasing the numbers of B cells in the marrow of the obese mice twofold, while doubling and tripling, respectively, the numbers of pre-B and immature B cells. Twelve days of supplementation brought these subpopulations to near-normal proportions. Leptin treatment also facilitated myelopoiesis such that the marrow of the obese mice contained normal numbers of monocytes and granulocytes after 7 days. Taken together, the data support an important role for leptin in sustaining lymphopoiesis and myelopoiesis.