Impaired phospholipases A2production by stimulated macrophages from patients with acute respiratory distress syndrome.
Biochim Biophys Acta
; 1802(11): 986-94, 2010 Nov.
Article
in En
| MEDLINE
| ID: mdl-20600872
ABSTRACT
The aim of this study was to investigate whether early phase of acute respiratory distress syndrome (ARDS) is associated with changes in immune response, either systemic or localized to the lung. ARDS and control mechanically ventilated patients, as well as healthy volunteers were studied. Alveolar macrophages (AMΦ) and blood monocytes (BM) were treated ex vivo with lipopolysaccharide (LPS), interferon-γ (IFNγ), and surfactant. Phospholipase A2 (PLA2) activity and TLR4 expression were evaluated as markers of cell response. AMΦ from ARDS patients did not respond upon treatment with either LPS or IFN-γ by inducing PLA2 production. On the contrary, upon stimulation, in control patients the intracellular PLA2, (mainly cPLA2) levels were increased, but secretion of PLA2 (mainly sPLA2-IIA) was observed only after treatment with LPS. Surfactant suppressed PLA2 production in cells from both groups of patients. Increased relative changes of total PLA2 activity and an upregulation of TLR4 expression upon stimulation was observed in BM from primary ARDS, control patients and healthy volunteers. In BM from secondary ARDS patients, however, no PLA2 induction was observed, with a concomitant down-regulation of TLR4 expression. Cytosolic PLA2, its activated form, p-cPLA2, and sPLA2-IIA were the predominant PLA2 types within the cells, while extracellularly only sPLA2-IIA was identified. These results support the concept of down-regulated innate immunity in early ARDS that is compartmentalized in primary and systemic in secondary ARDS. PLA2 isoforms could serve as markers of the immunity status in ARDS. Finally, our data highlight the role of surfactant in controlling inflammation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory Distress Syndrome
/
Monocytes
/
Macrophages, Alveolar
/
Phospholipases A2
Limits:
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Biochim Biophys Acta
Year:
2010
Document type:
Article
Affiliation country:
Greece
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS