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. 2018 Apr 3;128(5):1852–1866. doi: 10.1172/JCI89867

Figure 4. S100A8 recovery aggravates disease progression in ihTNF-tg S100A9–/– mice.

Figure 4

(A–C) Changes in body weight (A), grip strength (B), and swelling of forepaws (C) of dox-treated ihTNF-tg S100A9–/– mice compared with ihTNF-tg, S100A9–/–, or control mice. Data are shown as mean ± SEM of 3 independent experiments. n = 6 mice per group in each experiment. *P < 0.05; **P < 0.01; ***P < 0.001, 1-way ANOVA. (D) Control (upper images) or dox-treated (lower images) ihTNF-tg S100A9–/– mice (n = 5 for each group) were injected with Cy5.5-labeled anti-S100A8, and whole-body OI was recorded by FRI 24 hours later. Strong fluorescence intensities were detected in all paws and skin, indicating S100A8 protein recovery during chronic TNF-α stimulation. Nonspecific background signals in the liver and bladder indicate tracer degradation. (E and F) S100A8 and S100A9 immunostainings of skin (E) and forepaw toes (F) of ihTNF-tg S100A9–/– mice in the presence (6 weeks) or absence of dox confirm S100A8 recovery in the nail matrix, skin keratinocytes, and phagocytes. The lower 2 images in F are magnifications of boxes in middle images. Scale bars: 100 μm. (G, H) Cytospin preparations of bone marrow (G) and blood cells (H) of ihTNF-tg S100A9–/– or S100A9–/– mice treated with dox for 6 (G) or 3 weeks (H). Cells were stained for S100A8/S100A9 expression. Scale bars: 50 μm. In contrast with S100A9–/– mice, ihTNF-tg S100A9–/– animals showed a pronounced recovery of S100A8 protein in BMCs after dox stimulation (middle panel), which was abolished after removal of dox for 7 days (right panel). (H) Cytospin preparations of blood cells from dox-treated ihTNF-tg S100A9–/– mice compared with S100A9–/– and WT mice. Staining of blood cells for S100A8 showed a recovery of S100A8 protein in phagocytes, but not lymphocytes, after TNF-α induction.