E. Boichot et al., INHALED SUBSTANCE-P INDUCES ACTIVATION OF ALVEOLAR MACROPHAGES AND INCREASES AIRWAY RESPONSES IN THE GUINEA-PIG, Neuropeptides, 25(5), 1993, pp. 307-313
Guinea-pigs pretreated with phosphoramidon or saline were treated with
an aerosol of substance P (SP) or saline. 24 h later, the pulmonary i
nflation pressure (PIP) to substance P or to cumulative doses of acety
lcholine or of histamine was recorded. The PIP response to SP itself w
as significantly enhanced in animals treated with phosphoramidon + SP
as compared with phosphoramidon + saline (2.5-fold increase 1 min afte
r 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 g
uinea-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 ani
ons by alveolar macrophages in response to f-MLP was also enhanced aft
er 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 response
s and the production of superoxide anion were similar. Altogether thes
e results suggest that SP contributes to the bronchial hyper-responsiv
eness in asthma and this probably through activation of alveolar macro
phages.