OBJECTIVE AND DESIGN: Previous in vitro experiments demonstrated that acute-phase protein, alpha 1-antitrypsin (AAT), could act either as an enhancer or as a suppressor of lipopolysaccharide (LPS)-induced cell activation depending on treatment time. Here we investigate how AAT regulates inflammatory responses in the short term when administrated post LPS challenge. METHODS: Similar experimental setup was used both in vitro and in vivo: human monocytes and neutrophils were stimulated with LPS for 2 h followed by AAT for a total time of 4 h, and C57BL/6 mice were treated intranasally with LPS and 2 h later with AAT and sacrificed after 4 h. Bronchial lavage (BAL) and lung homogenates were analyzed using bio-plex cytokine assay. BAL cell counts were assessed. RESULTS: Within 4 h, AAT enhanced LPS-induced tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, and IL-8 release from monocytes and neutrophils. Mice challenged for 4 h with LPS followed by AAT at 2 h showed no changes in BAL cell counts and higher levels of almost all measured cytokines, specifically RANTES in BAL and IL-12, IL-13, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-10 levels in lung homogenates, than in mice treated with LPS only. CONCLUSION: Within the short term, AAT enhances the magnitude of LPS-induced specific cytokine/chemokine production, which may play an important role in amplification and resolution of acute-phase inflammatory reactions in vivo.
OBJECTIVE AND DESIGN: Previous in vitro experiments demonstrated that acute-phase protein, alpha 1-antitrypsin (AAT), could act either as an enhancer or as a suppressor of lipopolysaccharide (LPS)-induced cell activation depending on treatment time. Here we investigate how AAT regulates inflammatory responses in the short term when administrated post LPS challenge. METHODS: Similar experimental setup was used both in vitro and in vivo: human monocytes and neutrophils were stimulated with LPS for 2 h followed by AAT for a total time of 4 h, and C57BL/6 mice were treated intranasally with LPS and 2 h later with AAT and sacrificed after 4 h. Bronchial lavage (BAL) and lung homogenates were analyzed using bio-plex cytokine assay. BAL cell counts were assessed. RESULTS: Within 4 h, AAT enhanced LPS-induced tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, and IL-8 release from monocytes and neutrophils. Mice challenged for 4 h with LPS followed by AAT at 2 h showed no changes in BAL cell counts and higher levels of almost all measured cytokines, specifically RANTES in BAL and IL-12, IL-13, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-10 levels in lung homogenates, than in mice treated with LPS only. CONCLUSION: Within the short term, AAT enhances the magnitude of LPS-induced specific cytokine/chemokine production, which may play an important role in amplification and resolution of acute-phase inflammatory reactions in vivo.
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