Impaired phospholipases A₂production by stimulated macrophages from patients with acute respiratory distress syndrome.
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.
Hatzidaki
Eleana
E
Chemistry Department, University of Ioannina, 45100 Ioannina, Greece.
Nakos
George
G
Galiatsou
Eftychia
E
Lekka
Marilena E
ME
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D054467:Phospholipases A2 / Q000378:metabolism*; D012128:Respiratory Distress Syndrome / Q000201:enzymology* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D055815:Young Adult
D015415:Biomarkers; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma; D054467:Phospholipases A2