230:
IL-33 is a Potent Stimulus for Eosinophil Activation
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Elizabeth M McKernan, BS, Evelyn L Angulo, MD, Paul S Fichtinger, BS, Sameer K Mathur, MD PhD FAAAAI

RATIONALE: Increased IL-33 was recently shown to prolong eosinophil survival through activation. We sought to determine the relative potency of IL-33 in eosinophil activation by changes in cell surface markers, adhesion, and chemotaxis.

METHODS: Fresh blood eosinophils were purified from human subjects 18-55 years old, most with an allergic rhinitis diagnosis with or without mild asthma, and who were genotyped at the 17q21 locus (rs7216389). Eosinophils were stimulated with either IL-33 (1ng/mL), IL-5 (10ng/mL), IL-3 (10ng/mL), or eotaxin-1 (10ng/mL) for 1 to 4 hours. Eosinophil surface markers were analyzed by multicolor flow cytometry. Adhesion was assessed by culture on wells coated with VCAM-1, periostin, and ICAM-1. Chemotaxis was assessed by culture in the upper chamber of a transwell with IL-33 (10ng/mL) or eotaxin-1 (100ng/mL) in the bottom chamber, with counting of eosinophils migrated into bottom chamber.

RESULTS: Eosinophil stimulation with IL-33 resulted in statistically significantly higher fold-increases in surface expression of CD11b, CD18, CD66b, and ICAM-1 markers when compared to IL-3, IL-5, and eotaxin-1. IL-33 stimulated adhesion was significantly greater than IL-5 with ICAM-1 (p=0.003) or periostin (p=0.002) as substrate. In all subjects, IL-33 did not appear to stimulate chemotaxis. However, when subjects were examined by genotype at the 17q21 locus (rs7216389 SNP), the eosinophil chemotaxis to IL-33 from TT subjects approached statistical significance (p=0.078), while CT subjects did not (p=0.82).

CONCLUSIONS: IL-33 is a potent stimulus for eosinophil activity including upregulation of cell surface markers and adhesion. Interestingly, the IL-33 stimulated chemotaxis may be genotype dependent.