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 micrograms/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.
Boichot
E
E
Bio-Inova Res. Lab, Plaisir, France.
Lagente
V
V
Paubert-Braquet
M
M
Frossard
N
N
D000109:Acetylcholine / Q000494:pharmacology; D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008163:Luminescent Measurements; D008165:Luminol; D008168:Lung / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*
D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008165:Luminol; D006632:Histamine; D000109:Acetylcholine