Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital and Karolinska Institutet; Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Transfusion. 2014 Mar;54(3):602-12. doi: 10.1111/trf.12345. Epub 2013 Jul 28.
In connection with platelet (PLT) production, random but transient aggregates sometimes form in the newly produced units. The underlying mechanisms as well as the impact on cellular level of this phenomenon are unknown. Hypothetically, random occurrence of aggregates may induce biochemical changes leading to PLT activation and release of immunomodulatory factors from the PLTs.
PLTs were aliquoted and prepared with an automated system for PLT pooling (OrbiSac, Terumo BCT) for a three-arm nonpaired study design (n=8). Initially aggregated PLT units in SSP+ were selected by visual inspection and compared to unaffected PLT units stored in SSP+ or 100% plasma. Cellular, metabolic, and functional variables were analyzed, including the concentrations of RANTES, sCD40L, and sTWEAK in the bags during a 9-day storage period.
Isolated aggregated PLTs show signs of spontaneous activation and respond less efficiently to TRAP stimulation. RANTES, sCD40L, and sTWEAK accumulated in the various PLT units during storage but sCD40L and RANTES accumulated in the initially aggregated PLT units to higher concentrations than the reference units and PLTs stored in 100% plasma (p<0.001). Over time, the levels of sTWEAK increased more in the plasma storage environment compared with PLT units stored in SSP+ (p<0.001).
Our data indicate that random occurrence of aggregates may lead to higher activation level and increased release of immunomodulatory factors from the PLTs.
在血小板(PLT)生成过程中,新生成的单位中偶尔会形成随机但短暂的聚集物。这种现象的潜在机制及其对细胞水平的影响尚不清楚。从理论上讲,聚集物的随机发生可能会诱导生化变化,导致 PLT 激活并从 PLT 释放免疫调节因子。
将 PLT 等分并使用自动化系统(OrbiSac,Terumo BCT)进行 PLT 汇集制备,用于非配对的三臂研究设计(n=8)。最初通过视觉检查选择 SSP+中聚集的 PLT 单位,并将其与存储在 SSP+或 100%血浆中的未受影响的 PLT 单位进行比较。分析了细胞、代谢和功能变量,包括在 9 天储存期间袋子中 RANTES、sCD40L 和 sTWEAK 的浓度。
分离的聚集 PLT 显示自发激活的迹象,对 TRAP 刺激的反应效率较低。RANTES、sCD40L 和 sTWEAK 在储存过程中在各种 PLT 单位中积累,但 sCD40L 和 RANTES 在最初聚集的 PLT 单位中积累的浓度高于参考单位和存储在 100%血浆中的 PLT(p<0.001)。随着时间的推移,sTWEAK 的水平在血浆储存环境中比在 SSP+中储存的 PLT 单位中增加得更多(p<0.001)。
我们的数据表明,聚集物的随机发生可能导致 PLT 的激活水平更高,并释放更多的免疫调节因子。