Watt S M, Williamson J, Genevier H, Fawcett J, Simmons D L, Hatzfeld A, Nesbitt S A, Coombe D R
Medical Oncology Laboratory, Imperial Cancer Research Fund, London, UK.
Blood. 1993 Nov 1;82(9):2649-63.
The platelet-endothelial cell adhesion molecule-1 (PE-CAM-1), defined by the CD31 monoclonal antibody (MoAb), was initially described as a cell-cell adhesion molecule mediating both homotypic and heterotypic adhesion. In this report, we show that enriched CD34+ human hematopoietic progenitor cell populations, containing early myeloid, erythroid, and multipotential progenitor cells, are CD31+. Analyses of CD34+ cell lines representing early myeloid, multipotential, and pre-pre-B-lymphoid progenitors indicate that precursors of both myeloid and B-lymphoid cells express PECAM-1 at high levels. Three-color flow-cytometric analyses also show that normal human bone marrow CD31+ CD34+ subsets coexpress myeloid (CD33) or B-lymphoid (CD19, CD10) markers. Except for the monocytic cell line, U937, all CD34- cell lines tested, which represent more mature stages of the myeloid, erythroid, and lymphoid lineages, expressed substantially lower or negligible levels of PECAM-1. Western blotting studies indicated that the CD31 MoAb, JC/70A, detected molecules in the 120- to 140-kD molecular weight range on the monocytic CD34- CD33+ CD31+ cell line, U937; on the CD34+ CD31+ CD33+ CD19- multipotential/lymphomyeloid precursor cell lines, KG1 and KG1B; on the CD34+ CD31+ CD19+ CD10+ CD33- precursor pre-pre-B-cell line, MIK-ALL; and on a CD34(+)-enriched precursor cell population from normal human bone marrow. A single molecular weight species was generally observed with enriched membrane preparations, whereas two PECAM-1 molecules were present in whole-cell lysates of cell lines and the CD34+ bone marrow cell subset. Preliminary studies show that a proportion of the PECAM-1 molecules on the lymphomyeloid/multipotential progenitor cell line, KG1, and on the monocytic cell line, U937, binds to heparin-sepharose. A soluble form of PECAM-1 also binds heparin-sepharose. The high level of expression of PECAM-1 on CD34+ cells suggests that this glycoprotein may function as a heterotypic adhesion molecule, possibly mediating multipotential, myeloid, and early-B-lymphoid precursor cell interactions with stromal cells and extracellular matrix molecules via heparan sulfate proteoglycans. It may also act as a homotypic adhesion molecule by interacting with PECAM-1 on bone marrow stromal macrophage-like cells and endothelial cells or on endothelial cells during stem/progenitor cell migration. Thus, this molecule has the potential importance of directing both lineage commitment and trafficking of early hematopoietic progenitor cells.
血小板内皮细胞黏附分子-1（PE-CAM-1），由CD31单克隆抗体（MoAb）所定义，最初被描述为一种介导同型和异型黏附的细胞间黏附分子。在本报告中，我们表明，富含CD34⁺人类造血祖细胞群体，包含早期髓系、红系和多能祖细胞，是CD31⁺。对代表早期髓系、多能和前前B淋巴细胞祖细胞的CD34⁺细胞系的分析表明，髓系和B淋巴细胞的前体细胞均高水平表达PECAM-1。三色流式细胞术分析还显示，正常人骨髓CD31⁺CD34⁺亚群共表达髓系（CD33）或B淋巴细胞（CD19、CD10）标志物。除单核细胞系U937外，所有测试的CD34⁻细胞系，它们代表髓系、红系和淋巴系更成熟阶段，表达的PECAM-1水平显著更低或可忽略不计。蛋白质免疫印迹研究表明，CD31 MoAb，JC/70A，在单核细胞CD34⁻CD33⁺CD31⁺细胞系U937；CD34⁺CD31⁺CD33⁺CD19⁻多能/淋巴髓系前体细胞系KG1和KG1B；CD34⁺CD31⁺CD19⁺CD10⁺CD33⁻前体前前B细胞系MIK-ALL；以及正常人骨髓富含CD34(+)的前体细胞群体中，检测到分子量在120至140 kD范围内的分子。在用富含膜的制剂时通常观察到单一分子量的条带，而在细胞系和CD34⁺骨髓细胞亚群的全细胞裂解物中存在两种PECAM-1分子。初步研究表明，淋巴髓系/多能祖细胞系KG1和单核细胞系U937上的一部分PECAM-1分子与肝素琼脂糖结合。可溶性形式的PECAM-1也与肝素琼脂糖结合。PECAM-1在CD34⁺细胞上的高水平表达表明，这种糖蛋白可能作为一种异型黏附分子发挥作用，可能通过硫酸乙酰肝素蛋白聚糖介导多能、髓系和早期B淋巴细胞前体细胞与基质细胞和细胞外基质分子的相互作用。它也可能通过在干细胞/祖细胞迁移过程中与骨髓基质巨噬细胞样细胞和内皮细胞或内皮细胞上的PECAM-1相互作用，作为同型黏附分子发挥作用。因此，该分子在指导早期造血祖细胞的谱系定向和迁移方面可能具有重要意义。
