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PRAM-1 Is Required for Optimal Integrin-Dependent Neutrophil Function

机译：最佳的整合素依赖性中性粒细胞功能需要PRAM-1

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PML-retinoic acid receptor alpha (RARα) regulated adaptor molecule 1 (PRAM-1) is an intracellular adaptor molecule that is upregulated during the induced granulocytic differentiation of promyelocytic leukemic cells and during normal human myelopoiesis. This report describes the generation of PRAM-1-deficient mice and an analysis of the function of this adaptor in neutrophil differentiation and mature neutrophil function. We demonstrate here that neutrophil differentiation is not impaired in PRAM-1-deficient mice and that PRAM-1-deficient neutrophils function normally following engagement of Fcγ receptors. In contrast, mature PRAM-1-null neutrophils exhibit significant defects in adhesion-dependent reactive oxygen intermediate production and degranulation. Surprisingly, other integrin-dependent responses, such as cell spreading and activation of several signaling pathways, are normal. Together, these findings demonstrate the uncoupling of key integrin-dependent responses in the absence of PRAM-1 and show this adaptor to be critical for select integrin functions in neutrophils.
机译：PML-视黄酸受体α（RARα）调控的衔接分子1（PRAM-1）是一种细胞内衔接分子，在早幼粒白血病细胞的粒细胞分化诱导和正常人骨髓生成过程中被上调。该报告描述了缺乏PRAM-1的小鼠的产生，并分析了该衔接子在中性粒细胞分化和成熟中性粒细胞功能中的功能。我们在这里证明在PRAM-1缺陷小鼠中嗜中性粒细胞的分化不会受到损害，并且在Fcγ受体参与后PRAM-1缺陷中性粒细胞的功能正常。相比之下，成熟的PRAM-1-null中性粒细胞在依赖粘附的活性氧中间产物和脱粒过程中表现出明显的缺陷。令人惊讶地，其他整联蛋白依赖性反应，例如细胞扩散和几种信号传导途径的激活，是正常的。总之，这些发现证明了在不存在PRAM-1的情况下，关键整合素依赖性反应的解偶联，并且表明该衔接子对于嗜中性粒细胞中选择整合素的功能至关重要。

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