title: A two-event in vitro model of acute chest syndrome: the role of secretory phospholipase A2 and neutrophils.
abstract: BACKGROUND
  Acute chest syndrome (ACS) in sickle cell disease is associated with elevation of secretory phospholipase A(2) (sPLA(2) ). We hypothesize that sPLA(2) 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, sPLA(2) levels were measured, and the RBCs were incubated with sPLA(2) . Plasma and lipids, extracted from the plasma or the supernatant of sPLA(2) -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 sPLA(2) -IIa levels were associated with ACS. SPLA(2) -liberated lipids from VOC and the plasma, plasma lipids and sPLA(2) -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 sPLA(2) -released lipids from RBCs during VOC or ACS induce PMN-mediated ECI. VOC elicited increases in PS surface expression providing a membrane substrate for sPLA(2) lysis of sickle RBCs.
authors.affiliation: The Research Department, Bonfils Blood Center, 717 Yosemite Street, Denver, CO 80230, USA.
authors.forename: J Bradley
authors.initials: JB
authors.lastname: Ball
authors.forename: Samina Y
authors.initials: SY
authors.lastname: Khan
authors.forename: Nathan J D
authors.initials: NJ
authors.lastname: McLaughlin
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Kelher
authors.forename: Rachelle
authors.initials: R
authors.lastname: Nuss
authors.forename: Laura
authors.initials: L
authors.lastname: Cole
authors.forename: Xiayuan
authors.initials: X
authors.lastname: Liang
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D056586:Acute Chest Syndrome / Q000503:physiopathology*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003120:Colorado; D004730:Endothelium, Vascular; D005260:Female; D006801:Humans; D007223:Infant; D008168:Lung / Q000098:blood supply; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D054497:Phospholipases A2, Secretory / Q000097:blood*
chemical_list: D054497:Phospholipases A2, Secretory