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Activation of the human neutrophil 5‐lipoxygenase by exogenous arachidonic acid: involvement of pertussis toxin‐sensitive guanine nucleotide‐binding proteins
Author(s) -
McColl Shaun R.,
Krump Eric,
Naccache Paul H.,
Caon Adriana C.,
Borgeat Pierre
Publication year - 1989
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.1476-5381.1989.tb12588.x
Subject(s) - arachidonic acid , leukotriene b4 , pertussis toxin , biochemistry , hydroxyeicosatetraenoic acid , leukotriene , lipoxygenase , arachidonate 5 lipoxygenase , chemistry , biology , enzyme , immunology , inflammation , receptor , g protein , asthma
1 The mechanism by which incubation of human peripheral blood neutrophils with exogenous arachidonic acid leads to 5‐lipoxygenase product synthesis was investigated. 2 Incubation of neutrophils with arachidonic acid caused a concentration‐ and time‐dependent synthesis of leukotriene B 4 , its Ω‐oxidation products, and 5‐hydroxyeicosatetraenoic acid. 3 The threshold concentration of arachidonic acid required for this effect was equal to, or greater than 3.3 μ m and the synthesis increased with up to 33 μ m arachidonic acid, the highest concentration used. Synthesis induced by arachidonic acid increased with time for up to 15 min and the major products detected were the Ω‐oxidation products of leukotriene B 4 . 4 Pre‐incubation of neutrophils with pertussis toxin inhibited the synthesis of 5‐lipoxygenase products induced by arachidonic acid by 75% or more, but had no effect on either arachidonic acid‐induced synthesis of the 15‐lipoxygenase product, 15‐hydroxyeicosatetraenoic acid, or activation of the 5‐lipoxygenase induced by the calcium ionophore A23187. 5 Pre‐incubation of neutrophils with granulocyte‐macrophage colony‐stimulating factor lead to enhanced leukotriene synthesis in response to arachidonic acid. 6 These results imply that exogenous arachidonic acid is not only used as a substrate, but also activates the 5‐lipoxygenase. Possible mechanisms of action are discussed.