Platelet storage lesion accelerates desialylation of platelets and increases hepatic thrombopoietin production
Other Titles
혈소판 저장 병변에 의한 혈소판의 탈사이알릴화와 간세포의 트롬보포이에틴 합성 증가에 대한 규명
Authors
조주영
College
Graduate School, Yonsei University
Department
Dept. of Medicine
Degree
박사
Issue Date
2017
Abstract
Background: Stored platelets undergo deleterious changes, referred to as platelet
storage lesions (PSLs), which accelerate the desialylation of platelets and result in
their phagocytosis and clearance by hepatic macrophages. Recent studies have
reported that Ashwell-Morell receptor binds to desialylated platelets, thereby
inducing hepatic thrombopoietin (TPO) production in a mouse model. Therefore,
this study aimed to demonstrate these relationships between PSL and hepatic TPO
production in human study.
Methods: Platelet concentrates (PCs) were obtained from 5 healthy volunteers and
remaining samples in blood bank. PCs were divided into two halves, and stored
either at 22°C or 4°C. Experiments were conducted using serial samples.
Desialylation was assessed using flow cytometry, and structural changes were visualized using electron microscopy. Following co-culture of HepG2 cells (HB-
8065, ATCC) with isolated platelets, hepatic TPO production was determined using
real-time quantitative polymerase chain reaction (qPCR) and the supernatant TPO
level was measured using a Luminex kit.
Results: For 5 days of storage duration, platelet counts themselves were not
influenced by the storage conditions. The degree of desialylation was proportional
to the storage duration and dependent on hypothermal stress. Changes on platelet
surface and structure in electron microscope were significant according to storage
conditions. And HepG2 cells that reacted with aged or refrigerated platelets
expressed more TPO mRNA than those that reacted with fresh platelets. But, the
changes of supernatant TPO level were not significant.
Conclusions: This study demonstrated that, in vitro, aging and refrigeration affect
the integrity of human platelets, resulting in induction of hepatic TPO mRNA
expression, as proven in a mouse model.