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Guinea‐pig treatment with pertussis toxin suppresses macrophage‐dependent bronchoconstriction by fMLP and fails to inhibit the effects of PAF
Author(s) -
Kadiri Chakir,
Leduc Dominique,
Lefort Jean,
Imaizumi Atsushi,
Vargaftig B. Boris
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb13402.x
Subject(s) - bronchoconstriction , pertussis toxin , superoxide , in vivo , alveolar macrophage , thromboxane b2 , platelet activating factor , pharmacology , chemistry , immunology , g protein , biology , macrophage , in vitro , biochemistry , receptor , platelet , microbiology and biotechnology , asthma , enzyme
1 Bronchoconstriction and thromboxane B 2 (TxB 2 ) release following the intra‐tracheal administration of the secretagogue N‐formyl‐ l ‐methionyl‐ l ‐leucyl‐ l ‐phenylalanine (fMLP) to lungs from pertussis toxin‐treated guinea‐pigs in vivo and in vitro were inhibited as compared to saline‐treated animals, under conditions where the responses to PAF were modified less effectively. 2 The cell target accounting for bronchoconstriction by fMLP and for inhibition by pertussis toxin is located in the airways and is probably the alveolar macrophage. Indeed (a) fMLP‐induced superoxide anions and TxB 2 formation by alveolar macrophages were inhibited by pertussis toxin given in vivo; (b) G i proteins of membranes from alveolar macrophages were ADP‐ribosylated in vivo by pertussis toxin and (c) bronchoconstriction and TxB 2 release in response to the intra‐tracheal administration of fMLP to lungs from pertussis toxin‐treated animals were restored when alveolar macrophages from control guinea‐pigs were transferred into the airways of pertussis toxin‐treated animals before lung isolation. 3 Pertussis toxin administered to guinea‐pigs in vivo , reduced the subsequent TxB 2 formation and superoxide anion release by alveolar macrophages stimulated with PAF, but failed to inhibit PAF‐induced bronchoconstriction. 4 Formation of TxB 2 by alveolar macrophages following the intra‐tracheal administration of fMLP accounts for bronchoconstriction and requires pertussis toxin‐sensitive G i proteins. PAF operates via a different mechanism, which is independent of G i ‐like protein and involves mediators other than TxB 2 and superoxide anions.