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Alternaria alternata aeroallergens evoke ATP release and IL‐33 secretion from normal and asthmatic bronchial epithelial cells.
Author(s) -
O'Grady Scott M.,
Maniak Peter J.,
Lancto Cheryl,
Shivappa Nandadevi,
Kita Hirohito
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1166.18
Subject(s) - bafilomycin , secretion , intracellular , brefeldin a , chemistry , alternaria , pharmacology , biochemistry , biology , golgi apparatus , cell , apoptosis , genetics , autophagy
Exposure of human bronchial epithelial (HBE) cells from normal and asthmatic subjects to Alternaria alternata extract evoked rapid and sustained ATP release with greater efficacy observed in cells from asthmatic subjects. Previously, Alternaria aeroallergens were shown to elicit sustained increases in intracellular [Ca 2+ ] i that depended on coordinated activation of P2Y 2 and P2X 7 receptors. In this study, pretreatment with BAPTA‐AM inhibited ATP release, indicating dependency on increases in [Ca 2+ ] i . Alternaria ‐evoked ATP release exhibited a greater peak response and higher EC 50 value in cells obtained from asthmatic subjects compared to normal controls. Furthermore, the maximum increase in [Ca 2+ ] i was greater in cells from asthmatic subjects. The vesicle transport inhibitor brefeldin A blocked Alternaria ‐stimulated incorporation of fluorescent lipid (FM1–43) labeled vesicles into the plasma membrane and ATP release. Additionally, inhibiting vesicular ATP uptake with bafilomycin also blocked ATP release similar to brefeldin A. These results indicated that a primary mechanism for Alternaria ‐induced ATP release involved Ca 2+ ‐dependent vesicular transport. Serine and cysteine protease inhibitors also reduced Alternaria ‐induced ATP release. This result was consistent with our previous data showing that Alternaria ‐evoked increases in [Ca 2+ ] i depend on purinoceptor signaling.