Fig. 7: Myeloid cell-specific knockout of FPPS and TRPM2-KO effectively attenuates neutrophil infiltration and vascular permeability in mice. | Nature Communications

Fig. 7: Myeloid cell-specific knockout of FPPS and TRPM2-KO effectively attenuates neutrophil infiltration and vascular permeability in mice.

From: TNF inhibitors target a mevalonate metabolite/TRPM2/calcium signaling axis in neutrophils to dampen vasculitis in Behçet’s disease

Fig. 7

A Representative images of Evans-blue permeation on the dorsal skin of FPPSflox/flox LysMcre mice and FPPSflox/flox mice taken after induction of vasculitis. Rabbit serum was used as a background control. B Representative microphotographs of paraffin-embedded skin sections from FPPSflox/flox LysMcre mice and FPPSflox/flox mice with H&E staining. Blue arrows indicate neutrophils, and orange arrows indicate erythrocyte extravasation. Scale bar = 25 μm. C Quantification of Evans-blue penetration area in dorsal skin was standardized by the rabbit serum group, after vasculitis induction in FPPSflox/flox LysMcre mice and FPPSflox/flox mice (N = 6, 8 weeks old, 3 female and 3 male). D The number of perivascular neutrophils in HE-stained skin sections observed under a 40x objective microscope (N = 6). E, F Representative and summary of immunohistochemistry staining of MPO in skin tissues of FPPSflox/flox LysMcre mice and FPPSflox/flox mice with induced vasculitis (N = 6). Scare bar = 50 μm. G, H Representative and summary of immunofluorescence staining of MPO and Ly6G in skin tissues of FPPSflox/flox LysMcre mice and FPPSflox/flox mice with induced vasculitis (N = 6). Scare bar = 50 μm. IK Representative and summary of Evans-blue permeation on the dorsal skin of TRPM2 total knockout mice and control mice taken after induction of vasculitis (N = 4, 8 weeks old, 2 female and 2 male). Quantification of Evans-blue was obtained with Image J (J) and spectrophotometer (K), respectively. N for all experiments were biological replicates. Data are presented as mean ± SD; error bars indicate the SD. A two-sided p-value < 0.05 was considered statistically significant. Source data are provided as a Source Data file. *, p < 0.05. Independent t-tests were used in (C, D, F, H, and J, K).

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