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[Modulation of alveolar macrophage activity by ambroxol, bromhexine and exogenous arachidonic acid]
Abstract:
The increased generation of reactive oxygen metabolites (ROM) (O2-, H2O2, 1O2, X OH, OX-) by alveolar macrophages (AM) and neutrophils has been proposed as an important step in the pathogenesis of many acute and chronic lung disorders. With regard to a possible therapeutic application in this context the effect of bromhexine and ambroxol on the activity of AM of of guinea-pigs and of patients with lung diseases was investigated. The activity of AM, which were isolated by bronchoalveolar lavage, was determined by means of chemiluminescence (CL)-measuring. Ambroxol and bromhexine cause a depression of the spontaneous as well as of the induced CL [yeast cell walls, yeast glucan, exogenous arachidonic acid (AA)] of AM. AM from guinea-pigs and in some cases also from patients show primarily an increase of the CL-signal under the influence of bromhexine. These results suggest that ambroxol and bromhexine reduce the production of ROM by AM. The mechanism is possibly due to the activation of acyl-CoA-lysophosphatide acyltransferase. The increase of this enzyme activity lowers the intracellular concentration of the free AA, whereby the generation of ROM is diminished too. The investigations exhibit a new possibility of influence of respiratory burst and thus indirectly of AA-liberation from phospholipids. The probable reduction of AA-liberation by these drugs could also be of importance for other lung cells especially concerning the biosynthesis of eicosanoids (AA-metabolites), which play an important part as pathogenetic mediators in different lung diseases.
Insights
Bromhexine and ambroxol reduce reactive oxygen metabolite production by alveolar macrophages. This suggests a new therapeutic approach for lung diseases by influencing respiratory burst and arachidonic acid liberation.
Area of Science:
- Pulmonology
- Cell Biology
- Pharmacology
Background:
- Increased reactive oxygen metabolites (ROM) from alveolar macrophages (AM) contribute to lung disorder pathogenesis.
- Bromhexine and ambroxol are investigated for their therapeutic potential in lung diseases.
Purpose of the Study:
- To investigate the effect of bromhexine and ambroxol on AM activity.
- To explore their impact on ROM generation and potential therapeutic mechanisms.
Main Methods:
- Alveolar macrophages (AM) isolated via bronchoalveolar lavage from guinea-pigs and patients.
- AM activity assessed using chemiluminescence (CL) measurements.
- Spontaneous and induced CL (yeast cell walls, glucan, arachidonic acid) evaluated.
Main Results:
- Ambroxol and bromhexine decreased spontaneous and induced CL in AM.
- Bromhexine initially increased CL in some guinea-pig and patient AM.
- These drugs may reduce ROM production by activating acyl-CoA-lysophosphatide acyltransferase, lowering free arachidonic acid.
Conclusions:
- Ambroxol and bromhexine reduce ROM production by AM, potentially through influencing acyl-CoA-lysophosphatide acyltransferase.
- These drugs offer a novel way to modulate respiratory burst and arachidonic acid liberation.
- This mechanism may be significant for other lung cells, impacting eicosanoid biosynthesis in lung diseases.