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The p67 laminin receptor identifies human erythroid progenitor and precursor cells and is functionally important for their bone marrow lodgment

机译:p67层粘连蛋白受体可识别人类红细胞祖细胞和前体细胞在其骨髓lo存中起重要作用

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摘要

The laminins are a group of extracellular matrix proteins with constitutive expression in all tissues, including bone marrow stroma. A functional role for the nonintegrin laminin receptor p67 has been described for cancer metastasis and lymphocyte trafficking. Expression of p67 was also reported for other subsets of mature leukocytes and for malignant hematopoietic or nonhematopoietic cells. We explored p67 expression on normal hematopoietic progenitor cells (HPCs) and its putative role in bone marrow retention of transplanted HPCs. We found p67 expression on a subset of primary human CD34+ cells coexpressing erythroid markers. Of importance, p67 recognizes early erythroid progenitors, since sorted p67+ cells were significantly enriched for burst-forming units–erythroid (BFU-Es) and depleted of colony-forming units–granulocyte/macrophage (CFU-GMs). Blockade of p67 binding of donor cells, using antifunctional antibody, reduced bone marrow homing of BFU-Es. These studies identify p67 as a novel phenotypic marker for erythroid HPCs of functional importance for lineage-specific homing/retention among adult transplanted HPCs.
机译:层粘连蛋白是一组在包括骨髓基质在内的所有组织中组成性表达的细胞外基质蛋白。已经描述了非整联蛋白层粘连蛋白受体p67在癌症转移和淋巴细胞运输中的功能作用。还报道了p67的表达用于成熟白细胞的其他亚群以及恶性造血或非造血细胞。我们探讨了正常造血祖细胞(HPC)上的p67表达及其在移植的HPC的骨髓保留中的假定作用。我们在共表达红系标记的原代人CD34 + 细胞子集中发现p67表达。重要的是,p67可以识别早期的类红细胞祖细胞,因为分选的p67 + 细胞中的形成单元-红系(BFU-Es)明显丰富,而集落形成单元-粒细胞/巨噬细胞(CFU-总经理)。使用抗功能抗体阻断供体细胞与p67的结合,可减少BFU-E的骨髓归巢。这些研究将p67鉴定为类红细胞HPC的新型表型标记,对成人成年HPC中的谱系特异性归巢/保留功能具有重要的功能。

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