ZFIN Image: Roca et al., 2019, Figure 4

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Figure Caption

Figure 4

Ryanodine Receptor Mediates Macrophage Necrosis in Excess TNF Conditions

(A) Percentage of Rhod-2-positive macrophages in 1 dpi control and TNF-high larvae that are WT or expressing the BH4 domain of BCL-2 or BCL-XL. Horizontal bars, means; ^∗∗∗p < 0.001 (one-way ANOVA with Tukey’s post-test).

(B) Cording in 5 dpi TNF-high and control larvae that are WT or expressing the BH4 domain of BCL-2. ^∗p < 0.05; ^∗∗p < 0.01 (Fisher’s exact test). Representative of 3 independent experiments.

(C) Percentage of Rhod-2-positive macrophages in 1 dpi control and TNF-high larvae treated with xestospongin C (XestC) or ryanodine. Horizontal bars, means; ^∗∗∗p < 0.001 (one-way ANOVA with Tukey’s post-test). Representative of 2 independent experiments.

(D) Cording in 5 dpi TNF-high and control larvae treated with XestC or ryanodine. ^∗∗p < 0.01; ^∗∗∗p < 0.001 (Fisher’s exact test). Representative of 2 independent experiments.

(E) Percentage of larvae with cording among WT or siblings expressing the BH4 domain of BCL-XL injected with TNF. ^∗p < 0.05; ^∗∗∗p < 0.001 (Fisher’s exact test). Representative of 2 independent experiments.

(F) Percentage of Rhod-2-positive macrophages in 1 dpi control and TNF-high larvae treated with dantrolene. Horizontal bars, means; ^∗∗p < 0.01; ^∗∗∗p < 0.001 (one-way ANOVA with Tukey’s post-test).

(G) Cording in 5 dpi TNF-high and control larvae treated with dantrolene. ^∗∗∗p < 0.001 (Fisher’s exact test). Representative of 4 independent experiments.

(H) Representative confocal images of 3 day larvae expressing GCaMP3 targeted to the mitochondria of their macrophages which are red fluorescent, 2 h after administration of 4CmC larvae. Scale bar, 10 μm.

(I) Cording in 5 dpi TNF-high and control larvae that are WT or BAX mutant and treated with Ru360 and/or 4CmC. ^∗p < 0.05 (Fisher’s exact test). Representative of 2 independent experiments.

See also Table S1.

Acknowledgments

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Reprinted from Cell, 178(6), Roca, F.J., Whitworth, L.J., Redmond, S., Jones, A.A., Ramakrishnan, L., TNF Induces Pathogenic Programmed Macrophage Necrosis in Tuberculosis through a Mitochondrial-Lysosomal-Endoplasmic Reticulum Circuit, 1344-1361.e11, Copyright (2019) with permission from Elsevier. Full text @ Cell