RBL-2H3 cells are an imprecise model for mast cell mediator release

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RBL-2H3 cells are an imprecise model for mast cell mediator release (1)

Mast cells degranulate in response to peptidoglycan challenge through a TLR2-dependent pathway and are able to release newly synthesised cytokines [e.g., interleukin (IL)-13, IL-4 and TNF-a] after stimulation of TLR4 by lipopolysaccharide (LPS). RBL-2H3 cells have been exten- sively used for studying IgE–FceRI interactions [9], signalling pathways for degranulation and to test novel mast cell stabilisers.

Maximum release of b-hexosaminidase occurred at a concentration of 72.2 ng/ml of anti-DNP IgE with a value of 20.32 ± 0.8% of the total enzyme activity. Thereafter, increasing concentrations of anti-DNP IgE resulted in a progressively reduced release of b-hexosa- minidase, with 5,000 ng/ml of anti-DNP IgE releasing 7.0 ± 5.5%, representing 34.5% of the maximum value at 72.2 ng/ml anti-DNP IgE.

A23187 (5 ug/ml) was used to stimulate release of granular mediators resulting in 50% of total b-hexosaminidase release. MCDP and compound 48/80 both failed to produce any response. In our hands, quercetin at 10 uM reduced the amount of total enzyme release from 31.2 ± 1.8 to 4.5 ± 1.0%, (P < 0.01).

Lipopolysaccharide (Escherichia coli 0111:B4) at concentrations between 0.1 and 1 ug/ml failed to produce a cytokine response from RBL-2H3 cells.

Transcripts encoding TLR3, 4, 5 and 6 were detected in RBL-2H3 cells while messages for TLR1, 2, 8, 9 and 10 were absent. In RPMC, transcripts encoding TLR1, 2, 3, 4, 5, 6 and 8 but not TLR9 were detected.

After 3 days in culture, There was a significant difference in mean fluorescence intensity (MFI) between control values and those for TLR4, but signals for CD14 were found to be not statistically.

RBL-2H3 cells appear to be a reliable model to study IgE-mediated degranulation of secretory cells. They exhibit a bell-shaped dose-response curve to increasing concen- tration of anti-DNP IgE. The CD14 co-receptor needs to form a complex with TLR4 in order to allow further signalling. In this study we looked for CD14 expression in RBL-2H3 cells, and its absence is a likely explanation for the lack of response of the cells to LPS stimulation.

1. E. Passante, C. Ehrhardt, H. Sheridan, N. Frankish, RBL-2H3 cells are an imprecise model for mast cell mediator release. Inflamm. Res. 58, 611–618 (2009).

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