Effect of in vitro aspirin stimulation on basophils in patients with aspirin-exacerbated respiratory disease.
BACKGROUND
Basophil activation has been implicated in the pathogenesis of aspirin-exacerbated respiratory disease (AERD). However, a comprehensive analysis of basophil responses to aspirin in terms of mediator release, cytokine secretion and increased expression of surface activation markers has not been performed.


OBJECTIVE
To study the in vitro effects of aspirin on the concurrent release of histamine, leukotriene C4 (LTC4) and IL-4 from human basophils and to also evaluate changes in surface activation markers (CD63, CD69 and CD203c) expressed by these cells.


METHODS
Basophil-enriched cell suspensions from 10 patients with AERD and 10 healthy volunteers were incubated with lysine-aspirin for up to 3 h. Cells were analysed for expression of CD63, CD69 and CD203c using flow cytometry. Cell-free supernatants were evaluated for histamine, and LTC4 release and for IL-4 secretion.


RESULTS
Aspirin-induced expression of CD63, CD69 and CD203c yielded 30%, 80% and 70% sensitivity, respectively, but with poor specificity. There was no significant difference in LTC4 synthesis between groups. None of the patients with AERD (or controls) released IL-4 in response to aspirin. A higher dose of 5 mg/mL aspirin-mediated non-specific effects on basophils.


CONCLUSIONS
Basophil responses to in vitro aspirin challenge are poor indicators of clinical sensitivity. Aspirin activates some basophils by means of mechanisms that differ from the classical IgE-mediated pathway. Our study also shows that the use of 27 mm of aspirin (5 mg/mL) by previous investigators causes non-specific basophil activation, thereby eliminating its usefulness in a cell-based diagnostic test for AERD. Evaluation of in vitro basophil activation has low clinical value in identifying aspirin-induced respiratory reactions.
Celik
G E
GE
Ankara University School of Medicine, Division of Allergy, Ankara, Turkey. gulfemcelik@gmail.com
Schroeder
J T
JT
Hamilton
R G
RG
Saini
S S
SS
Adkinson
N F
NF
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015703:Antigens, CD; D001241:Aspirin / Q000494:pharmacology*; D055963:Asthma, Aspirin-Induced / Q000378:metabolism* / Q000473:pathology; D001491:Basophils / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D017997:Leukotriene C4 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; C508598:IL4 protein, human; D015847:Interleukin-4; D017997:Leukotriene C4; D006632:Histamine; D001241:Aspirin