Figure 1.
Figure 1. PBN prevents lethality and attenuates colonic tissue damage after anti-CD40 antibody administration in syngeneic bone marrow transplant recipients. (A) Lethally irradiated (1000 cGy) B6 mice received transplants of B6 BM cells and were then treated with either rat IgG (▪, n = 10) or anti-CD40 antibody (8 μg/d) for 4 days beginning on day one after transplantation. Mice treated with anti-CD40 were administered either PBN (□, n = 16) or DMSO (•, n = 16) twice daily for 6 days beginning on the day of BMT. Actual survival is depicted. Data are cumulative results from 4 independent experiments. Statistics: P < .001, for IgG/PBN (▪) versus CD40/DMSO (•) and CD40/PBN (□) versus CD40/DMSO (•); P = not significant (NS), for IgG/PBN (•) versus CD40/PBN (□). (B) Mean weights of mice depicted in panel A. (C) Lethally irradiated B6 mice received transplants of B6 BM cells and then administered either IgG/PBN (n = 6; open bar), CD40/DMSO (n = 10; shaded bar), or CD40/PBN (n = 9; solid bar). Mice were killed on day 4 after BMT after the completion of anti-CD40 treatment. Tissue samples of the colon were obtained and graded using a pathology score as described in “Study design.” Data are presented as the mean histologic score ± SEM in colons of individual mice. Data are cumulative results from 2 independent experiments. (D-F) H and E stains of colonic tissues obtained from recipients 4 days after transplantation (original magnification, × 200). (D) IgG/PBN-treated mouse showing normal-appearing colonic tissue with intact crypts lined by mucin-filled enterocytes. (E) CD40/DMSO-treated mouse with extensive degenerative changes in surface-lining enterocytes and significant loss of goblet cells. Crypts have become cystic and contain cellular debris and neutrophils. (F) CD40/PBN-treated mouse with colonic mucosa showing increased mitotic activity of lining epithelial cells. In comparison with panel E, there is reduced loss of mucin in enterocytes and significantly less cellular debris in the crypt lumens. Microscope used was a Nikon Eclipse E400, with a Nikon Plan APO 10×/0.45 lens, and a Zeiss Axiom camera. Software used included Axiovision 3.0.6 SPZ.

PBN prevents lethality and attenuates colonic tissue damage after anti-CD40 antibody administration in syngeneic bone marrow transplant recipients. (A) Lethally irradiated (1000 cGy) B6 mice received transplants of B6 BM cells and were then treated with either rat IgG (▪, n = 10) or anti-CD40 antibody (8 μg/d) for 4 days beginning on day one after transplantation. Mice treated with anti-CD40 were administered either PBN (□, n = 16) or DMSO (•, n = 16) twice daily for 6 days beginning on the day of BMT. Actual survival is depicted. Data are cumulative results from 4 independent experiments. Statistics: P < .001, for IgG/PBN (▪) versus CD40/DMSO (•) and CD40/PBN (□) versus CD40/DMSO (•); P = not significant (NS), for IgG/PBN (•) versus CD40/PBN (□). (B) Mean weights of mice depicted in panel A. (C) Lethally irradiated B6 mice received transplants of B6 BM cells and then administered either IgG/PBN (n = 6; open bar), CD40/DMSO (n = 10; shaded bar), or CD40/PBN (n = 9; solid bar). Mice were killed on day 4 after BMT after the completion of anti-CD40 treatment. Tissue samples of the colon were obtained and graded using a pathology score as described in “Study design.” Data are presented as the mean histologic score ± SEM in colons of individual mice. Data are cumulative results from 2 independent experiments. (D-F) H and E stains of colonic tissues obtained from recipients 4 days after transplantation (original magnification, × 200). (D) IgG/PBN-treated mouse showing normal-appearing colonic tissue with intact crypts lined by mucin-filled enterocytes. (E) CD40/DMSO-treated mouse with extensive degenerative changes in surface-lining enterocytes and significant loss of goblet cells. Crypts have become cystic and contain cellular debris and neutrophils. (F) CD40/PBN-treated mouse with colonic mucosa showing increased mitotic activity of lining epithelial cells. In comparison with panel E, there is reduced loss of mucin in enterocytes and significantly less cellular debris in the crypt lumens. Microscope used was a Nikon Eclipse E400, with a Nikon Plan APO 10×/0.45 lens, and a Zeiss Axiom camera. Software used included Axiovision 3.0.6 SPZ.

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