IL-33 synergizes with IgE-dependent and IgE-independent agents to promote mast cell and basophil activation

MR Silver, A Margulis, N Wood, SJ Goldman… - Inflammation …, 2010 - Springer
MR Silver, A Margulis, N Wood, SJ Goldman, M Kasaian, D Chaudhary
Inflammation research, 2010Springer
Objective Mast cell and basophil activation contributes to inflammation, bronchoconstriction,
and airway hyperresponsiveness in asthma. Because IL-33 expression is inflammation
inducible, we investigated IL-33-mediated effects in concert with both IgE-mediated and IgE-
independent stimulation. Methods Because the HMC-1 mast cell line can be activated by
GPCR and RTK signaling, we studied the effects of IL-33 on these pathways. The IL-33-and
SCF-stimulated HMC-1 cells were co-cultured with human lung fibroblasts and airway …
Objective
Mast cell and basophil activation contributes to inflammation, bronchoconstriction, and airway hyperresponsiveness in asthma. Because IL-33 expression is inflammation inducible, we investigated IL-33-mediated effects in concert with both IgE-mediated and IgE-independent stimulation.
Methods
Because the HMC-1 mast cell line can be activated by GPCR and RTK signaling, we studied the effects of IL-33 on these pathways. The IL-33- and SCF-stimulated HMC-1 cells were co-cultured with human lung fibroblasts and airway smooth muscle cells in a collagen gel contraction assay. IL-33 effects on IgE-mediated activation were studied in primary mast cells and basophils.
Result
IL-33 synergized with adenosine, C5a, SCF, and NGF receptor activation. IL-33-stimulated and SCF-stimulated HMC-1 cells demonstrated enhanced collagen gel contraction when cultured with fibroblasts or smooth muscle cells. IL-33 also synergized with IgE receptor activation of primary human mast cells and basophils.
Conclusion
IL-33 amplifies inflammation in both IgE-independent and IgE-dependent responses.
Springer