Bonig Halvard, Chang Kai-Hsin, Nakamoto Betty, Papayannopoulou Thalia
University of Washington, Departmen of Medicine/Hematology, Seattle, WA 98195-7720, USA.
Blood. 2006 Aug 15;108(4):1230-3. doi: 10.1182/blood-2005-12-013508. Epub 2006 Apr 11.
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.
层粘连蛋白是一组细胞外基质蛋白,在包括骨髓基质在内的所有组织中都有组成性表达。非整合素层粘连蛋白受体p67在癌症转移和淋巴细胞运输方面的功能作用已被描述。p67在其他成熟白细胞亚群以及恶性造血或非造血细胞中的表达也有报道。我们研究了正常造血祖细胞(HPCs)上p67的表达及其在移植HPCs骨髓滞留中的假定作用。我们发现p67在共表达红系标志物的原代人CD34(+)细胞亚群上表达。重要的是,p67识别早期红系祖细胞,因为分选的p67(+)细胞中红系爆式集落形成单位(BFU-Es)显著富集,而粒细胞/巨噬细胞集落形成单位(CFU-GMs)减少。使用抗功能抗体阻断供体细胞的p67结合,可降低BFU-Es的骨髓归巢。这些研究确定p67是成年移植HPCs中对谱系特异性归巢/滞留具有功能重要性的红系HPCs的一种新型表型标志物。