Impaired phospholipases Aproduction by stimulated macrophages from patients with acute respiratory distress syndrome
| Autor: | Hatzidaki, E., Nakos, G., Galiatsou, E., Lekka, M. E. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Phospholipases A2/*metabolism Biological Markers/metabolism Blotting Western Macrophages Alveolar/drug effects/*enzymology Interferon-gamma/pharmacology Middle Aged Flow Cytometry Lipopolysaccharides/pharmacology Monocytes/drug effects/*enzymology Young Adult Toll-Like Receptor 4/metabolism Humans Female Respiratory Distress Syndrome Adult/*enzymology/immunology Cells Cultured Aged |
| Popis: | 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 (AMPhi) and blood monocytes (BM) were treated ex vivo with lipopolysaccharide (LPS), interferon-gamma (IFNgamma), and surfactant. Phospholipase A (PLA) activity and TLR4 expression were evaluated as markers of cell response. AMPhi from ARDS patients did not respond upon treatment with either LPS or IFN-gamma by inducing PLA production. On the contrary, upon stimulation, in control patients the intracellular PLA, (mainly cPLA) levels were increased, but secretion of PLA (mainly sPLA-IIA) was observed only after treatment with LPS. Surfactant suppressed PLA production in cells from both groups of patients. Increased relative changes of total PLA 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 PLA induction was observed, with a concomitant down-regulation of TLR4 expression. Cytosolic PLA, its activated form, p-cPLA, and sPLA-IIA were the predominant PLA types within the cells, while extracellularly only sPLA-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. PLA isoforms could serve as markers of the immunity status in ARDS. Finally, our data highlight the role of surfactant in controlling inflammation. Biochim Biophys Acta |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|