[Modulation of alveolar macrophage activity by ambroxol, bromhexine and exogenous arachidonic acid].
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.
D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001964:Bromhexine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006168:Guinea Pigs; D008163:Luminescent Measurements; D008171:Lung Diseases / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects*; D008563:Membrane Lipids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology*; D013481:Superoxides / Q000378:metabolism
D001095:Arachidonic Acids; D008563:Membrane Lipids; D010743:Phospholipids; D013481:Superoxides; D000551:Ambroxol; D016718:Arachidonic Acid; D001964:Bromhexine
Modulation der Alveolarmakrophagenaktivität durch Ambroxol, Bromhexin und exogene Arachidonsäure.