Occupational asthma due to western red cedar is associated with histamine release from basophils and mast cells on exposure to plicatic acid (PA), but the mechanisms underlying this response remain unclear.
Specific kinase inhibitors were used to study the role of tyrosine and serine/threonine kinases in PA-induced histamine release from human basophils.
Pretreatment with the tyrosine kinase inhibitor methyl 2,5-dihydroxy-cinnamate (MDHC) attenuated histamine release from basophils triggered by anti-IgE (29.8% inhibition ; n=15 ; P<0.01) or grass pollen (48% inhibition ; n=6 ; P<0.01).
Inhibition was concentration-dependent and could be reversed by washing the cells in buffer, while the inactive stereoisomer of MDHC did not affect histamine release.
In contrast, the protein kinase C inhibitor staurosporin did not affect histamine release by either anti-IgE or grass pollen.
Pretreatment with MDHC partially inhibited PA-induced histamine release from basophils of 6/9 patients with red cedar asthma (25.4% vs 33.8% ; P=NS).
Staurosporin gave a similar level of inhibition of PA-induced histamine release (25.3% vs 33.8% ; P=NS).
Thus, signal transduction of the human basophil FCERI appears to depend upon tyrosine kinase activation, but not on protein kinase C (serine/threonine kinase) activation. (...)
Mots-clés Pascal : Asthme, Allergie, Basophile, Granulocyte, Libération, Histamine, Dégranulation, Exposition professionnelle, Thuja plicata, Coniferales, Gymnospermae, Spermatophyta, Protein-tyrosine kinase, Transferases, Enzyme, Inhibiteur enzyme, Relation dose réponse, Pathogénie, Canada, Amérique du Nord, Amérique, Homme, Appareil respiratoire pathologie, Immunopathologie, Leucocyte, Maladie professionnelle, Médecine travail, Plicatique acide
Mots-clés Pascal anglais : Asthma, Allergy, Basophil, Granulocyte, Release, Histamine, Degranulation, Occupational exposure, Thuja plicata, Coniferales, Gymnospermae, Spermatophyta, Protein-tyrosine kinase, Transferases, Enzyme, Enzyme inhibitor, Dose activity relation, Pathogenesis, Canada, North America, America, Human, Respiratory disease, Immunopathology, Leukocyte, Occupational disease, Occupational medicine
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 98-0162201
Code Inist : 002B06C02. Création : 21/07/1998.