The acute chest syndrome (ACS) is a form of acute lung injury (ALI) unique to sickle cell disease (SCD), and for children > 10 years represents the major cause of morbidity and mortality. Although most ALI is thought to be neutrophil (PMN)-mediated, the role of the PMN in ACS remains unknown. ACS has been linked to increases in plasma secretory phospholipase A2-IIA (sPLA2-IIA) activity within 24 hours of its development (

Styles et al
Blood
87
:
2573
–8,
1996
). We hypothesize that sPLA2-IIA cleavage of membrane lipids releases lipophilic compounds that prime PMNs and provoke ACS in patients SCD. After obtaining informed consent, heparinized whole blood was drawn from children with SCD when well, at their annual comprehensive clinic visit, and serially when admitted to the hospital, upon admission and every other day until discharge. Plasma was isolated, divided, and stimulated with buffer or sPLA2 for 30 minutes at 37°C. The lipids were extracted and assayed for their ability to prime fMLP-activation of the PMN oxidase quantitated by the rate of O2− production determined by the SOD-inhibitable reduction of cytochrome c at 550 nm. The data (mean ± the standard error of the mean of lipid priming activity at baseline and during hospitalization, see Table) consists of three groups: patients with SCD: patients with no chronic treatment (SCD), patients treated with daily hydroxyurea (+HU), and patients treated with monthly red cell exchanges (+EX). At baseline, there was significant lipid priming activity in untreated patients (SCD) versus either +HU- or +EX-treated patients. The lipid priming decreased in patients with vaso-occlusive disease (VOD = pain crisis) and became significantly different in the four patients with ACS as comapred to their baseline samples. Moreover, 12 hours prior to developing ACS one hospitalized patient demonstrated an increase in sPLA2-IIA liberated lipid priming activity (1.0– to 1.7–fold). We conclude that

  1. both HU and EX therapies appear to diminish baseline sPLA2-IIA release of lipid activity in children with SCD as comapred to the untreated SCD group,

  2. during the time period prior to development of ACS, the sPLA2-IIA release of lipid priming activity increased as compared to baseline, and

  3. when ACS is diagnosed, sPLA2-IIA release of lipid priming activity is statistically increased as compared to baseline lipid priming. These data demonstrate an association between the sPLA2-IIA release of bioactive lipids and ACS, a relationship seen in other forms of ALI including both TRALI and ARDS. Furthermore, the PMN may play a role in ACS but not in VOD. These data need to be corroborated in a larger study of SCD patients in a multi-institutional trial.

Lipid Priming Activity in Plasma from SCD patients

Treat./DiagnosisBaselineVODACS
§= p<.05 vs. HU and EX baseline; †=p<.05 vs SCD baseline. 
SCD 2.3±0.4§ 1.3±0.1 3.4±0.4† 
SCD + HU 1.6±0.2 1.4±0.3 No data 
SCD + EX 1.5±0.2 1.8±0.2 No data 
Treat./DiagnosisBaselineVODACS
§= p<.05 vs. HU and EX baseline; †=p<.05 vs SCD baseline. 
SCD 2.3±0.4§ 1.3±0.1 3.4±0.4† 
SCD + HU 1.6±0.2 1.4±0.3 No data 
SCD + EX 1.5±0.2 1.8±0.2 No data 
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Topics:
acute chest syndrome, lipids, neutrophils, sickle cell anemia, veno-occlusive disease, secretory phospholipase a2, acute lung injury, buffers, cytochrome c, hydroxyurea

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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