The effect of tyrosine kinase inhibitors on IgE-mediated histamine release from human lung mast cells and basophils.
OBJECTIVE
To investigate the role of tyrosine kinases (TK) in IgE-mediated signal transduction in human lung mast cells (HLMC) and basophils.


METHODS
Peripheral blood basophils (n > or = 4) and human lung mast cells (n > or = 6).


METHODS
Cells were preincubated with TK inhibitor for 15 min at 37 degrees C, before the addition of anti-IgE.


METHODS
Histamine release (HR) was assayed using a fluorimetric technique. Results were compared using nonparametric statistics.


RESULTS
Piceatannol and ST638 significantly (p < or = 0.05) inhibited anti-IgE induced HR from HLMCs and basophils whilst lavendustin C had no effect in either cell type. Herbimycin A also significantly (p < or = 0.05) inhibited anti-IgE induced HR from both cell types, an effect which was dose dependent but did require a 16 h preincubation with drug.


CONCLUSIONS
In summary, HLMCs and basophils exhibit distinct inhibitory profiles in the presence of various inhibitors of TK.
Lavens-Phillips
S E
SE
Johns Hopkins Asthma & Allergy Center, Division of Clinical Immunology, Baltimore, MD 21224, USA. selp@welchlink.welch.jhu.edu
Mockford
E H
EH
Warner
J A
JA
D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D016227:Benzoquinones; D002452:Cell Count / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*; D047029:Lactams, Macrocyclic; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology
D016227:Benzoquinones; D002934:Cinnamates; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D010636:Phenols; D010975:Platelet Aggregation Inhibitors; D011809:Quinones; D013267:Stilbenes; D013440:Sulfides; C060747:ST 638; C080022:lavendustin C6; D017828:Rifabutin; D007073:Immunoglobulin E; C041525:3,3',4,5'-tetrahydroxystilbene; C020754:herbimycin; D011505:Protein-Tyrosine Kinases