成功的造血细胞移植(HCT)取决于将重建造血的祖细胞和干细胞的快速植入。Rap1A和Rap1B是两种密切相关的小GTP酶,可能通过其在细胞粘附和迁移中的作用影响HCT期间的血小板和中性粒细胞移植。β-肾上腺素能信号传导可能通过抑制或激活来调节Rap1A和Rap1B参与植入。我们进行了一项随机对照试验的相关研究,该试验评估了非选择性β-拮抗剂普萘洛尔对25例接受自体HCT治疗多发性骨髓瘤患者中性粒细胞和血小板植入过程中Rap1A和Rap1B表达和戊烯化的影响。在HCT之前1周和之后4周施用普萘洛尔。在HCT前7天(基线)和2天(第2天)采集血液,和HCT后28天(第+28天)。分离循环的多形核细胞(PMNC)并通过免疫印迹分析以确定戊烯化的水平和总Rap1A与Rap1B的水平。12名参与者被随机分配到干预措施中,13名参与者被随机分配到对照组中。Rap1A表达与Rap1B表达显著相关。Rap1B表达与较慢的血小板植入显着相关;然而,在普萘洛尔治疗组中未观察到这种关联.中性粒细胞植入与Rap1A或Rap1B表达之间没有显著关联。事后探索性分析未揭示社会健康变量与Rap1A或Rap1B表达之间的关联。这项研究确定了Rap1B在血小板移植中的调节作用比Rap1A更大,并暗示了β-肾上腺素能信号在调节HCT期间Rap1B功能中的可能作用。
Successful hematopoietic cell transplantation (HCT) depends on rapid engraftment of the progenitor and stem cells that will reestablish hematopoiesis. Rap1A and Rap1B are two closely related small GTPases that may affect platelet and neutrophil engraftment during HCT through their roles in cell adhesion and migration. β-adrenergic signaling may regulate the participation of Rap1A and Rap1B in engraftment through their inhibition or activation. We conducted a correlative
study of a randomized controlled
trial evaluating the effects of the nonselective β-antagonist propranolol on expression and prenylation of Rap1A and Rap1B during neutrophil and platelet engraftment in 25 individuals receiving an autologous HCT for multiple myeloma. Propranolol was administered for 1 week prior to and 4 weeks following HCT. Blood was collected 7 days (baseline) and 2 days (Day -2) before HCT, and 28 days after HCT (Day +28). Circulating polymorphonuclear cells (PMNC) were isolated and analyzed via immunoblotting to determine levels of prenylated and total Rap1A versus Rap1B. Twelve participants were randomized to the intervention and 13 to the control. Rap1A expression significantly correlated with Rap1B expression. Rap1B expression significantly correlated with slower platelet engraftment; however, this association was not observed in the propranolol-treated group. There were no significant associations between neutrophil engraftment and Rap1A or Rap1B expression. Post hoc exploratory analyses did not reveal an association between social health variables and Rap1A or Rap1B expression. This
study identifies a greater regulatory role for Rap1B than Rap1A in platelet engraftment and suggests a possible role for β-adrenergic signaling in modulating Rap1B function during HCT.