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首页> 外文期刊>Journal of Cellular Physiology >Modulation of the adhesion of hemopoietic progenitor cells to the RGD site of fibronectin by interleukin 3.
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Modulation of the adhesion of hemopoietic progenitor cells to the RGD site of fibronectin by interleukin 3.

机译:调制的造血的附着力祖细胞纤连蛋白的RGD网站白介素3。

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摘要

The integrins are a class of adhesion molecules which have been implicated in the homing of hemopoietic stem cells and in their restriction within the bone marrow. Integrins function as mediators of cell-extracellular matrix (ECM) interactions amd also of cell-cell interactions. They are unique membrane receptors which are capable of activation, change in affinity, and change in expression. Because of their broad potential for modulation we examined the effect of a cytokine growth factor which is present constitutively in the marrow, interleukin 3 (IL3), on integrin-mediated adherence of hemopoietic progenitor cells to the matrix component fibronectin (FN). The multipotential murine cell line B6Sut and the committed granulocyte progenitor cell line FDCP-1 were used. Both of these cell lines have been shown to bind to FN-coated dishes and to dishes coated with the 120 kDa and 40 kDa chymotryptic fragments of FN. It was found that after a brief withdrawal of IL3 the cells lost 80% adherence to the 120 kDa FN fragment containing the RGD cell binding site. This loss of binding was not related to a loss of viability, appeared unrelated to the growth/survival activity of IL3, and was quickly reversible by readdition of the growth factor. Adhesion of these cells to the RGD site was likely mediated by alpha 5 beta 1 integrin which was identified in the cell membrane of both cell lines, but present in low copy number in B6Sut cells. Two antibodies against the external and internal domains of alpha 5 and one antibody against beta 1 were used to study expression of the integrin. By flow cytometry the expression of alpha 5 was found to decrease in both cell lines by 4 h in the absence of IL3. The relative mean fluorescence intensity for B6Sut cells decreased from 1.0 (control cells always in the presence of IL3) to 0.6 over 4 h, and for FDCP-1 cells the decrement was from 1.0 to 0.8. The loss of RGD-mediated adhesion in the absence of IL3 appeared to proceed through this decrement in expression of the integrin; a loss of affinity of the receptor for its substrate was not detected. The general modulation of integrin activity by growth factors is of great interest because of its potential negative impact on the endothelium in cytokine-treated patients, and also because of its potential positive impact on engraftment during clinical bone marrow transplantation.
机译:整合蛋白是一类粘附分子已被卷入的归航造血干细胞和限制在骨髓中。介质cell-extracellular矩阵(ECM)amd的交互信息的交互。他们是独特的膜受体激活的能力,亲和力,变化表达的变化。潜力调制我们检查效果细胞因子生长因子的存在既定的骨髓,白介素3(IL3) integrin-mediated依从性造血祖细胞矩阵组件纤连蛋白(FN)。鼠科动物细胞系B6Sut和承诺粒细胞FDCP-1祖细胞系使用。结合涂布FN-coated盘子和碗120 kDa 40 kDa糜蛋白酶的FN的碎片。坚持撤军IL3细胞失去了80%120 kDa FN包含RGD细胞碎片结合位点。生存能力的丧失,出现了与IL3的增长/生存活动无关,readdition快速可逆的生长因子。网站可能是由α5β1整合素是细胞中识别膜的细胞系,但出现在低拷贝数在B6Sut细胞。对内部和外部域的α5和1抗体beta 1研究整合素的表达。血细胞计数的表达α5被发现减少4 h两个细胞系的缺席IL3。从1.0(控制细胞B6Sut细胞减少总是在IL3) 0.6 / 4 h,从1.0和FDCP-1细胞衰减到0.8。缺乏IL3似乎进行这一衰减在整合素的表达;受体的亲和力的衬底没有检测到。活动由生长因子是极大的兴趣由于其潜在的负面影响在cytokine-treated患者内皮,也因为它的潜在的积极影响在临床骨髓移植移植。

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