SUBSTANCE-P AND ALVEOLAR MACROPHAGES - EFFECTS ON OXIDATIVE-METABOLISM AND EICOSANOID PRODUCTION

The tachykinin substance P (SP) is present in lung sensory nerve endin gs and may be released after neurogenic stimulation. Its role in the p athogenesis of asthma is still unclear. Nevertheless, it may play a ma jor role in airway neurogenic inflammation. Alveolar macrophages are t he predominant cells of the airway space and are involved in various t ypes of airway inflammation. We studied guinea pig alveolar macrophage response to SP and other related peptide (C- and N-terminal sequences , NK1-receptor agonist) stimulation. Alveolar guinea pig macrophages w ere recovered by bronchoalveolar lavage (BAL). Macrophage reactive oxy gen intermediate (ROI) production was studied by luminol-dependent che miluminescence with several concentrations of SP and related peptides. Eicosanoid synthesis after stimulation was evaluated by thin-layer ch romatography (TLC) and enzyme-linked immunosorbent assay (ELISA). SP, C-terminal sequence, and NK1-receptor agonist significantly increased ROI production by alveolar macrophages (P<0.01). NK1-agonist and C-ter minal sequence modified arachidonic acid metabolism and induced a sign ificant increase in prostaglandin (PG)D-2 synthesis (211% and 66%, res pectively). We concluded that SP and related peptides directly affect guinea pig alveolar macrophages by inducing the production of inflamma tory metabolites.