Slayton W B, Juul S E, Calhoun D A, Li Y, Braylan R C, Christensen R D
Department of Pediatrics, University of Florida College of Medicine, Gainesville 32610, USA.
Pediatr Res. 1998 Jun;43(6):774-82. doi: 10.1203/00006450-199806000-00010.
During human development, the liver and marrow both function as hematopoietic organs, but little is known about differences in the production of macrophages and neutrophils by these two organs. We used immunohistochemical stains to quantify the ratio of neutrophils to macrophages within the liver and the marrow of 16 fetuses from 5 to 16 wk postconception. At 5 wk the liver had a ratio of one granulocyte [myeloperoxidase (MPO)-positive cell] to every 9 +/- 5 (X +/- SD) macrophages (KP-1-positive cells). Between 5 and 16 wk, the granulocyte to macrophage ratio in the liver was constant, whereas it changed markedly in the marrow. Before 8 wk no MPO-positive or KP-1-positive cells were observed in bones. At 10 wk, bones still had no MPO-positive cells, but KP-1-positive cells were abundant. At 11-12 wk the granulocyte to macrophage ratio was 1 to 1 +/- 1, but by 13-16 wk it had increased to 8 +/- 3 MPO-positive cells to one KP-1-positive cell. We hypothesized that at 13-16 wk the abundance of MPO-positive cells in the marrow and their scarcity in the liver was the result of production of granulocyte colony-stimulating factor (G-CSF) and its receptor (G-CSF-R) in the marrow and their absence in the liver. However, by reverse transcriptase-PCR mRNAs for G-CSF and G-CSF-R were positive in both organs at all gestations, and G-CSF and G-CSF-R proteins (by immunohistochemistry) were also abundant in all liver and marrow specimens. We then hypothesized that progenitors in the fetal liver were intrinsically different from those in the marrow, and were unable to generate clones of neutrophils. However, progenitors from the liver produced neutrophils abundantly in culture. Thus, the explanation is likely related to as yet undescribed environmental differences between the fetal liver and marrow.
在人类发育过程中，肝脏和骨髓均发挥造血器官的功能，但对于这两个器官产生巨噬细胞和中性粒细胞的差异却知之甚少。我们使用免疫组织化学染色法对16例孕龄为5至16周胎儿的肝脏和骨髓中的中性粒细胞与巨噬细胞的比例进行定量分析。在孕5周时，肝脏中粒细胞[髓过氧化物酶（MPO）阳性细胞]与每9±5（X±SD）个巨噬细胞（KP-1阳性细胞）的比例为1∶1。在5至16周期间，肝脏中粒细胞与巨噬细胞的比例保持恒定，而骨髓中的这一比例则发生显著变化。在孕8周之前，未在骨骼中观察到MPO阳性或KP-1阳性细胞。在孕10周时，骨骼中仍无MPO阳性细胞，但KP-1阳性细胞数量丰富。在孕11至12周时，粒细胞与巨噬细胞的比例为1∶1±1，但到孕13至16周时，该比例已增至8±3个MPO阳性细胞比1个KP-1阳性细胞。我们推测，在孕13至16周时，骨髓中MPO阳性细胞数量丰富而肝脏中数量稀少是由于骨髓中产生粒细胞集落刺激因子（G-CSF）及其受体（G-CSF-R），而肝脏中缺乏所致。然而，通过逆转录聚合酶链反应（RT-PCR）发现，在所有孕周，G-CSF和G-CSF-R的信使核糖核酸在两个器官中均呈阳性，并且通过免疫组织化学检测发现，G-CSF和G-CSF-R蛋白在所有肝脏和骨髓标本中也均大量存在。随后我们推测，胎儿肝脏中的祖细胞与骨髓中的祖细胞本质上不同，无法产生中性粒细胞克隆。然而，来自肝脏的祖细胞在培养中能大量产生中性粒细胞。因此，其原因可能与胎儿肝脏和骨髓之间尚未明确的环境差异有关。
