Abstract
In order to explore the depressant action of ambroxol, a bronchial expectorant, on the activated alveolar macrophage responses, its effect on lipopolysaccharide (LPS)- or N-formyl-methionyl-leucyl-phenylalanine (fMLP)- stimulated free radical production and granule enzyme release by rat lung alveolar macrophages was investigated. Ambroxol attenuated the 100 ng/ml LPS- or 1 μm fMLP-stimulated superoxide. H2O2 and nitric oxide production and releases of acid phosphatase and lysozyme by alveolar macrophages. Ambroxol attenuated phorbol myristate acetate-stimulated superoxide and nitric oxide production that was inhibited by 100 nM staurosporine. N,N-dimethylsphingosine (DMS, 4.5 and 9 μM) alone stimulated superoxide production by macrophages, while 45 μM of the compound did not show a stimulatory effect. However, DMS decreased nitric oxide production in a dose-dependent manner. Ambroxol did not alter the DMS effect on free radical production that was affected by 10 μM genistein. A preincubation of macrophages with ambroxol (10 and 100 μM), staurosporine and genistein attenuated the elevation of [Ca2+](i) caused by LPS. The results suggest that ambroxol exerts a depressant effect on LPS- or fMLP-stimulated free radical production and granule enzyme release by rat alveolar macrophages, which may be attributed to its inhibitory action on the activation process, protein kinase C, but its action on protein tyrosine kinase is not suggested.
Original language | English (US) |
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Pages (from-to) | 275-284 |
Number of pages | 10 |
Journal | Pulmonary Pharmacology and Therapeutics |
Volume | 12 |
Issue number | 5 |
DOIs | |
State | Published - Oct 1999 |
Externally published | Yes |
Keywords
- Alveolar macrophages
- Ambroxol
- Functional responses
- LPS
- fMLP
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Biochemistry, medical
- Pharmacology (medical)