MOLECULAR-CLONING OF A CDNA-ENCODING INTERLEUKIN-11, A STROMAL CELL-DERIVED LYMPHOPOIETIC AND HEMATOPOIETIC CYTOKINE
MOLECULAR-CLONING OF A CDNA-ENCODING INTERLEUKIN-11, A STROMAL CELL-DERIVED LYMPHOPOIETIC AND HEMATOPOIETIC CYTOKINE
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DOI：
10.1073/pnas.87.19.7512
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发表时间：
1990-10-01
影响因子：
11.1
通讯作者：
YANG, YC
中科院分区：
文献类型：
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作者：
PAUL, SR;BENNETT, F;YANG, YC
造血发生与一个复杂的细胞网络密切相关，松散地称为造血微环境。微环境的复杂性以及造血干细胞和早期祖细胞的异质性阻碍了对造血微环境调控机制的分析。我们已经建立了永生化的灵长类动物骨髓源性基质细胞系，以便于分析造血细胞与大型动物物种微环境的相互作用。发现一种这样的细胞系PU-34产生多种生长因子，包括刺激白细胞介素6依赖性鼠浆细胞瘤细胞系增殖的活性。通过在哺乳动物细胞中的功能表达克隆，分离了编码浆细胞瘤刺激活性的cDNA。该核苷酸序列含有一个597个核苷酸的单一长阅读框，编码预测的199个氨基酸的多肽。 该细胞因子命名为白细胞介素11（IL-11），其氨基酸序列与GenBank数据库中的任何其他序列均无显著相似性。初步的生物学特性表明，除了刺激浆细胞瘤增殖外，IL-11还刺激产生免疫球蛋白的B细胞的T细胞依赖性发育，并与IL-3协同支持鼠巨核细胞集落形成。这些性质暗示IL-11作为造血微环境中的额外多功能调节剂。
Hematopoiesis occurs in close association with a complex network of cells loosely termed the hematopoietic microenvironment. Analysis of the mechanisms of microenvironmental regulation of hematopoiesis has been hindered by the complexity of the microenvironmental as well as the heterogeneity of hematopoietic stem cells and early progenitor cells. We have established immortalized primate bone marrow-derived stromal cells lines to facilitate analysis of the interactions of hematopoietic cells with the microenvironment in a large animal species. One such line, PU-34, was found to produce a variety of growth factors, including an activity that stimulates the proliferation of an interleukin 6-dependent murine plasmacytoma cell line. A cDNA encoding the plasmacytoma stimulatory activity was isolated through functional expression cloning in mammalian cells. The nucleotide sequence contained a single long reading frame of 597 nucleotides encoding a predicted 199-amino acid polypeptide. The amino acid sequence of this cytokine, designated interleukin 11 (IL-11), did not display significant similarity with any other sequence in the GenBank data base. Preliminary biological characterization indicates that in addition to stimulating plasmacytoma proliferation, IL-11 stimulates the T-cell-dependent development of immunoglobulin-producing B cells and synergizes with IL-3 in supporting murine megakaryocyte colony formation. These properties implicate IL-11 as an additional multifunctional regulator in the hematopoietic microenvironment.