Systemic effects of allergen exposure on blood basophil IL-13 secretion and FcepsilonRIbeta.
BACKGROUND
Airway allergen challenge studies have shown the upregulation of cytokines in local airway tissues and distal effects on bone marrow precursors for eosinophils and basophils.


OBJECTIVE
We investigated whether local intranasal allergen challenge alters the phenotype of circulating basophils to a primed state.


METHODS
Ten subjects with allergic rhinitis were challenged with allergen by means of intranasal spray on 3 sequential days. Basophils were isolated from subjects before challenge and 3, 24, and 96 hours after the third allergen challenge. Basophils were compared before challenge and after the last allergen challenge for levels of FcepsilonRIbeta protein by means of Western blotting and for FcepsilonRIbeta mRNA expression by means of real-time PCR. Basophils were also compared with regard to spontaneous secretion of IL-4 and IL-13.


RESULTS
Basophil FcepsilonRIbeta protein levels increased in 5 of 6 subjects after allergen challenge relative to before challenge. Likewise, basophil FcepsilonRIbeta mRNA levels increased a median of 2-fold after the last challenge relative to before challenge ( P=.007, n=9). IL-13 protein was detected in supernatants of 7 of 9 subjects' basophil-enriched cultures after the last challenge compared with 3 of 9 basophil-enriched cultures before challenge (median, 6.2 vs 0 pg/mL; P=.058). IL-4 was not detected in any culture supernatant.


CONCLUSIONS
Intranasal allergen challenge transiently activates circulating basophils by increasing expression of the FcepsilonRIbeta subunit and spontaneous IL-13 secretion. Because FcepsilonRIbeta is an amplifier of FcepsilonRI-mediated responses and IL-13 is proinflammatory, these findings support a primed basophil functional state and demonstrate a systemic effect of local allergen challenge that could contribute in exacerbating allergic reactions.
Department of Medicine, Division of Allergy and Clinical Immunology, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA. ssaini@jhmi.edu
Sarbjit
S
Saini
D Candy
DC
Bloom
Anja
A
Bieneman
Kavitha
K
Vasagar
Alkis
A
Togias
John
J
Schroeder
D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology*; D031164:Ambrosia / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology*; D019684:Magnoliopsida / Q000276:immunology*; D031784:Phleum / Q000276:immunology; D017455:Receptors, IgE / Q000096:biosynthesis / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D018793:Interleukin-13; D017455:Receptors, IgE