INHALED SUBSTANCE-P INDUCES ACTIVATION OF ALVEOLAR MACROPHAGES AND INCREASES AIRWAY RESPONSES IN THE GUINEA-PIG

Guinea-pigs pretreated with phosphoramidon or saline were treated with an aerosol of substance P (SP) or saline. 24 h later, the pulmonary inflation pressure (PIP) to substance P or to cumulative doses of acetylcholine or of histamine was recorded. The PIP response to SP itself was significantly enhanced in animals treated with phosphoramidon + SP as compared with phosphoramidon + saline (2.5-fold increase 1 min after the end of the inhalation, P < 0.001). The response to acetylcholine and to histamine was also significantly enhanced in phosphoramidon + substance P-treated as compared with phosphoramidon + saline-treated guinea-PigS (PC200 = 38.9 and 1.6 as compared with 77.6 and 3.9 mug/ml, P < 0.01 and P < 0.05 respectively). The production of superoxide anions by alveolar macrophages in response to f-MLP was also enhanced after treatment with phosphoramidon + SP as compared with phosphoramidon + saline (6.4 +/- 0.7 and 3.8 +/- 0.3 cpm, P < 0.001 respectively). In animals treated with saline + SP or saline + saline, the PIP responses and the production of superoxide anion were similar. Altogether these results suggest that SP contributes to the bronchial hyper-responsiveness in asthma and this probably through activation of alveolar macrophages.