Acute chest syndrome (ACS) in sickle cell disease is associated with elevation of secretory phospholipase A2 (sPLA2). We hypothesize that sPLA2 cleaves membrane lipids from sickled red blood cells (RBCs) causing PMN-mediated endothelial cell injury (ECI) as the second event in a two-event model.Methods.
Whole 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, sPLA2 levels 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.Results.
Increased 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.Conclusions.
ACS 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 sPLA2 lysis of sickle RBCs. Pediatr Blood Cancer 2012; 58: 399–405. © 2011 Wiley Periodicals, Inc.