Is tyrosine kinase activation involved in basophil histamine release in asthma due to western red cedar?

Authors

  • A. Frew,

    Corresponding author
    1. Respiratory Division, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
    2. University Medicine, Southampton General Hospital, Southampton, UK
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  • H. Chan,

    1. Respiratory Division, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
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  • H. Salari,

    1. Respiratory Division, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
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  • M. Chan-Yeung

    1. Respiratory Division, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
    2. Member of Canadian Respiratory Health Network of Centres of Excellence
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Dr A. J. Frew University Medicine (810) Southampton General Hospital Southampton SO 16 6YD UK

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 machanisms underlying this response remain unclear. Specific kinase inhibitors were used to study the role of 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 (25.4% vs 33.8%; P=NS). Thus, signal trasduction of the human basophil FcERI 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.

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