IL-3 induces basophil expansion in vivo by directing granulocyte-monocyte progenitors to differentiate into basophil lineage-restricted progenitors in the bone marrow and by increasing the number of basophil/mast cell progenitors in the spleen.

IL-3 induces basophil expansion in vivo by directing granulocyte-monocyte progenitors to differentiate into basophil lineage-restricted progenitors in the bone marrow and by increasing the number of basophil/mast cell progenitors in the spleen.
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DOI:
10.4049/jimmunol.0802870
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发表时间:
2009-03-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Huang H
Huang H
中科院分区:
其他
文献类型:
--
作者:
Ohmori K;Luo Y;Jia Y;Nishida J;Wang Z;Bunting KD;Wang D;Huang H

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最近的工作已经确定了嗜碱性粒细胞在调节免疫反应中的重要作用。为了发挥其生物学功能,嗜碱性粒细胞需要扩增到临界数量。然而,嗜碱性粒细胞扩增的机制尚不清楚。在这项研究中,我们确定了IL-3在嗜碱性粒细胞的快速和特异性扩增中发挥了重要作用。我们发现,IL-3复合物(IL-3 +抗IL-3抗体)极大地促进了粒细胞/单核细胞祖细胞(GMP)分化为嗜碱性粒细胞谱系限制性祖细胞(BaPs),但不能分化为嗜酸性粒细胞谱系限制性祖细胞(EoPs)或骨髓中的肥大细胞。我们还发现IL-3复合物处理导致脾脏中嗜碱性粒细胞/肥大细胞祖细胞(BMCP)的数量增加约4倍。IL-3驱动的嗜碱性粒细胞扩增依赖于信号转导和转录激活因子5(STAT 5)信号传导。我们发现,GMP,而不是共同的髓系祖细胞(CMP)表达低水平的IL-3受体。IL-3受体表达在BaPs中显著上调,但在EoPs中没有。约38%的BMCP表达IL-3Rα链。上调的IL-3受体表达不受IL-3或STAT 5的影响。我们的研究结果表明,IL-3诱导特异性扩增的嗜碱性粒细胞通过指导GMP分化成BaPs在骨髓中,并通过增加BMCP在脾脏中的数量。
Recent work has established important roles for basophils in regulating immune responses. To exert their biological functions, basophils need to be expanded to critical numbers. However, the mechanisms underlying basophil expansion remain unclear. In this study, we established that IL-3 played an important role in the rapid and specific expansion of basophils. We found that the IL-3 complex (IL-3 + anti-IL-3 antibody) greatly facilitated the differentiation of granulocyte/monocyte progenitor (GMPs) into basophil lineage-restricted progenitors (BaPs) but not into eosinophil lineage-restricted progenitors (EoPs) or mast cells in the bone marrow. We also found that the IL-3 complex treatment resulted in about 4-fold increase in the number of basophil/mast cell progenitors (BMCPs) in the spleen. IL-3-driven basophil expansion depended on signal transducer and activator of transcription 5 (STAT5) signaling. We showed that GMPs but not common myeloid progenitors (CMPs) expressed low levels of IL-3 receptor. IL-3 receptor expression was dramatically upregulated in BaPs but not EoPs. About 38% of BMCPs expressed the IL-3Rα chain. The upregulated IL-3 receptor expression was not affected by IL-3 or STAT5. Our findings demonstrate that IL-3 induced specific expansion of basophils by directing GMPs to differentiate into BaPs in the bone marrow and by increasing the number of BMCPs in the spleen.
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