Figure 6.
Figure 6. Effects of Mer inhibition on GVHD and TA-TMA of liver and kidney in mouse HSCT models Mouse HSCT models intravenously received 3 mg/kg UNC2250 at 14 days after HSCT, and the mouse models were sacrificed on day 21 after HSCT. (A) Mixed chimerism was determined by flow cytometry with anti HLA-antibodies, UNC2250 had no effect on engraftment in the HSCT mice. (B) The body weight of the recipient mice was assessed on the clinical findings using clinical GVHD scores. Body weight loss of the recipient mice was abrogated by intravenous administration of UNC2250. Data are expressed as mean ± SD (n = 9). **P < .01. (C) The levels of serum Gas6 were significantly increased in HSCT mice, using a mouse Gas6 ELISA kit. Data are expressed as mean ± SD (n = 9). *P < .05. (D) UNC2250 downregulated the expression of Gas6 and Mer in the livers of mouse HSCT models, using analysis of liver lysates samples by western blot. Representative data from 3 similar experiments are shown. (Ea-d) The intravenous administration of UNC2250 downregulated the expression of Gas6 and Mer in the mouse HSCT models. Immunohistochemical staining of Gas6 and Mer. Scale bars represent 5 µm. Original magnification ×200. (Fa-b) Macroscopic observations show that a formation of multiple nodules (arrows) was caused by inflammatory response in hepatic GVHD in mouse HSCT models. Intravenous administration of UNC2250 inhibited the characteristic findings of hepatic GVHD in the mouse HSCT models. (G) Hematoxylin and eosin (HE) stain. Scale bars represent 10 µm. Original magnification ×200. Histopathological findings showed that intravenous administration of UNC2250 markedly inhibited histological features of hepatic GVHD showing hepatocellular necrosis, fibrosis, and apoptosis in mouse HSCT models at 21 days after HSCT. (H) TUNEL staining analysis showed that apoptosis of liver cells was substantially reduced in the UNC2250-administered group compared with the non-UNC2250 group. Scale bars represent 5 µm. Original magnification ×200. (I-J) Histopathologic observations showed that formations of thrombi in hepatic and renal vessels were increased in mouse HSCT models at 21 days after HSCT, and intravenous administration of 3 mg/kg UNC2250 significantly suppressed the formations of thrombi in hepatic and renal vessels as compared with the group without treatment. Arrows indicate thrombi formation in vessels of the liver and kidney. Scale bars represent 10 µm. Original magnification ×200.

Effects of Mer inhibition on GVHD and TA-TMA of liver and kidney in mouse HSCT models Mouse HSCT models intravenously received 3 mg/kg UNC2250 at 14 days after HSCT, and the mouse models were sacrificed on day 21 after HSCT. (A) Mixed chimerism was determined by flow cytometry with anti HLA-antibodies, UNC2250 had no effect on engraftment in the HSCT mice. (B) The body weight of the recipient mice was assessed on the clinical findings using clinical GVHD scores. Body weight loss of the recipient mice was abrogated by intravenous administration of UNC2250. Data are expressed as mean ± SD (n = 9). **P < .01. (C) The levels of serum Gas6 were significantly increased in HSCT mice, using a mouse Gas6 ELISA kit. Data are expressed as mean ± SD (n = 9). *P < .05. (D) UNC2250 downregulated the expression of Gas6 and Mer in the livers of mouse HSCT models, using analysis of liver lysates samples by western blot. Representative data from 3 similar experiments are shown. (Ea-d) The intravenous administration of UNC2250 downregulated the expression of Gas6 and Mer in the mouse HSCT models. Immunohistochemical staining of Gas6 and Mer. Scale bars represent 5 µm. Original magnification ×200. (Fa-b) Macroscopic observations show that a formation of multiple nodules (arrows) was caused by inflammatory response in hepatic GVHD in mouse HSCT models. Intravenous administration of UNC2250 inhibited the characteristic findings of hepatic GVHD in the mouse HSCT models. (G) Hematoxylin and eosin (HE) stain. Scale bars represent 10 µm. Original magnification ×200. Histopathological findings showed that intravenous administration of UNC2250 markedly inhibited histological features of hepatic GVHD showing hepatocellular necrosis, fibrosis, and apoptosis in mouse HSCT models at 21 days after HSCT. (H) TUNEL staining analysis showed that apoptosis of liver cells was substantially reduced in the UNC2250-administered group compared with the non-UNC2250 group. Scale bars represent 5 µm. Original magnification ×200. (I-J) Histopathologic observations showed that formations of thrombi in hepatic and renal vessels were increased in mouse HSCT models at 21 days after HSCT, and intravenous administration of 3 mg/kg UNC2250 significantly suppressed the formations of thrombi in hepatic and renal vessels as compared with the group without treatment. Arrows indicate thrombi formation in vessels of the liver and kidney. Scale bars represent 10 µm. Original magnification ×200.

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