Dercksen M W, Gerritsen W R, Rodenhuis S, Dirkson M K, Slaper-Cortenbach I C, Schaasberg W P, Pinedo H M, von dem Borne A E, van der Schoot C E
European Cancer Centre, Amsterdam, The Netherlands.
Blood. 1995 Jun 1;85(11):3313-9.
Adhesion molecules play a role in the migration of hematopoietic progenitor cells and regulation of hematopoiesis. To study whether the mobilization process is associated with changes in expression of adhesion molecules, the expression of CD31, CD44, L-selectin, sialyl Lewisx, beta 1 integrins very late antigen 4 (VLA-4) and VLA-5, and beta 2 integrins lymphocyte function-associated 1 and Mac-1 was measured on either bone marrow (BM) CD34+ cells or on peripheral blood CD34+ cells mobilized with a combination of granulocyte colony-stimulating factor (G-CSF) and chemotherapy. beta 1 integrin VLA-4 was expressed at a significantly lower concentration on peripheral blood progenitor cells than on BM CD34+ cells, procured either during steady-state hematopoiesis or at the time of leukocytapheresis. No differences in the level of expression were found for the other adhesion molecules. To obtain insight in which adhesion molecules may participate in the homing of peripheral blood stem cells (PBSCs), the number of CD34+ cells expressing these adhesion molecules present in leukocytapheresis material was quantified and correlated with hematopoietic recovery after intensive chemotherapy in 27 patients. The number of CD34+ cells in the subset defined by L-selectin expression correlated significantly better with time to platelet recovery after PBSC transplantation (r = -.86) than did the total number of CD34+ cells (r = -.55). Statistical analysis of the relationship between the number of CD34+L-selectin+ cells and platelet recovery resulted in a threshold value for rapid platelet recovery of 2.1 x 10(6) CD34+ L-selectin+ cells/kg. A rapid platelet recovery (< or = 14 days) was observed in 13 of 15 patients who received > or = 2.1 x 10(6) CD34+ L-selectin+ cells/kg (median, 11 days; range, 7 to 16 days), whereas 10 of 12 patients who received less double positive cells had a relative slow platelet recovery (median, 20 days; range, 13 to 37 days). The L-selectin+ subpopulation of CD34+ cells also correlated better with time to neutrophil recovery (r = -.70) than did the total number of reinfused CD34+ cells (r = -.51). However, this latter difference failed to reach statistical significance. This study suggests that L-selectin is involved in the homing of CD34+ cells after PBSC transplantation.
黏附分子在造血祖细胞的迁移和造血调节中发挥作用。为研究动员过程是否与黏附分子表达的变化相关,我们检测了骨髓(BM)CD34+细胞或经粒细胞集落刺激因子(G-CSF)与化疗联合动员的外周血CD34+细胞上CD31、CD44、L-选择素、唾液酸化路易斯x、β1整合素极迟抗原4(VLA-4)和VLA-5以及β2整合素淋巴细胞功能相关抗原1和Mac-1的表达。在稳态造血期间或白细胞单采时获取的外周血祖细胞上,β1整合素VLA-4的表达浓度显著低于BM CD34+细胞。其他黏附分子的表达水平未发现差异。为深入了解哪些黏附分子可能参与外周血干细胞(PBSCs)的归巢,我们对白细胞单采材料中表达这些黏附分子的CD34+细胞数量进行了定量,并将其与27例患者强化化疗后的造血恢复情况进行了关联分析。由L-选择素表达定义的亚群中CD34+细胞数量与PBSC移植后血小板恢复时间的相关性(r = -0.86)显著优于CD34+细胞总数与血小板恢复时间的相关性(r = -0.55)。对CD34+L-选择素+细胞数量与血小板恢复之间关系的统计分析得出,快速血小板恢复的阈值为2.1×10⁶个CD34+L-选择素+细胞/kg。在接受≥2.1×10⁶个CD34+L-选择素+细胞/kg的15例患者中,有13例观察到快速血小板恢复(≤14天)(中位数为11天;范围为7至16天),而在接受较少双阳性细胞的12例患者中,有10例血小板恢复相对较慢(中位数为20天;范围为13至37天)。CD34+细胞的L-选择素+亚群与中性粒细胞恢复时间的相关性(r = -0.70)也优于回输的CD34+细胞总数与中性粒细胞恢复时间的相关性(r = -0.51)。然而,后一差异未达到统计学显著性。本研究提示L-选择素参与了PBSC移植后CD34+细胞的归巢。