title: Is tyrosine kinase activation involved in basophil histamine release in asthma due to western red cedar?
abstract: 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 staurosporine 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). Staurosporine 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 Fc epsilon RI appears to depend upon tyrosine kinase activation, but not on protein kinase C (serine/threonine kinase) activation. The lack of specific effect on plicatic acid-induced histamine release in basophils obtained from patients with occupational asthma due to western red cedar suggests that tyrosine kinases are not as important in this disease as in atopic asthma, and is consistent with the view that histamine release in red cedar asthma is largely IgE-independent.
authors.affiliation: Department of Medicine Vancouver General Hospital, University of British Columbia, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Frew
authors.forename: H
authors.initials: H
authors.lastname: Chan
authors.forename: H
authors.initials: H
authors.lastname: Salari
authors.forename: M
authors.initials: M
authors.lastname: Chan-Yeung
mesh_terms: D000485:Allergens / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism*; D001491:Basophils / Q000378:metabolism*; D002934:Cinnamates / Q000494:pharmacology; D004781:Environmental Exposure; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism; D017705:Lignans; D009284:Naphthols / Q000276:immunology; D006109:Poaceae; D011058:Pollen / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014197:Trees / Q000276:immunology*
chemical_list: D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D002934:Cinnamates; D004791:Enzyme Inhibitors; D006633:Histamine Antagonists; D017705:Lignans; D009284:Naphthols; C026408:anti-IgE antibodies; C067472:methyl 2,5-dihydroxycinnamate; D006632:Histamine; D011505:Protein-Tyrosine Kinases; C008938:plicatic acid