A two-event in vitro model of acute chest syndrome: the role of secretory phospholipase A2 and neutrophils.
A two-event in vitro model of acute chest syndrome: the role of secretory phospholipase A2 and neutrophils.
复制标题
急性胸部综合征的双事件体外模型：分泌性磷脂酶 A2 和中性粒细胞的作用。
DOI：
10.1002/pbc.23265
复制
发表时间：
2012
影响因子：
3.2
通讯作者：
Silliman,ChristopherC
中科院分区：
文献类型：
--
作者：
Ball,JBradley;Khan,SaminaY;McLaughlin,NathanJD;Kelher,MargueriteR;Nuss,Rachelle;Cole,Laura;Liang,Xiayuan;Silliman,ChristopherC
BackgroundAcute chest syndrome (ACS) in sickle cell disease is associated with elevation of secretory phospholipase A2(sPLA2). We hypothesize that sPLA2cleaves membrane lipids from sickled red blood cells (RBCs) causing PMN‐mediated endothelial cell injury (ECI) as the second event in a two‐event model.MethodsWhole blood was collected from children when in steady state or daily during admissions for vaso‐occlusive pain (VOC) or ACS. The plasma and RBCs were separated, sPLA2levels were measured, and the RBCs were incubated with sPLA2. Plasma and lipids, extracted from the plasma or the supernatant of sPLA2‐treated RBCs, were assayed for PMN priming activity and used as the second event in a model of PMN‐mediated ECI. Phosphatidylserine (PS) surface expression on RBCs was quantified by flow cytometry.ResultsIncreased sPLA2‐IIa levels were associated with ACS. SPLA2‐liberated lipids from VOC and the plasma, plasma lipids and sPLA2‐liberated lipids from ACS primed PMNs and caused PMN‐mediated ECI (P< 0.01). RBCs from VOC had increased in PS surface expression versus steady state.ConclusionsACS plasma and lipids and sPLA2‐released lipids from RBCs during VOC or ACS induce PMN‐mediated ECI. VOC elicited increases in PS surface expression providing a membrane substrate for sPLA2lysis of sickle RBCs. Pediatr Blood Cancer 2012; 58: 399–405. © 2011 Wiley Periodicals, Inc.
