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A mouse model of interstitial pneumonitis induced by murine cytomegalovirus infection after allogeneic skin transplantation.

Ni D, Yu H, Zhang W, Gan L, Zhao J, Wang M, Chen J - Biomed Res Int (2013)

Bottom Line: Flow cytometry showed that the number of CD4(+) and CD8(+) cells and the level of IFN- γ decreased significantly in the groups treated with cyclosporin A.Transmission electronic microscopy demonstrated the presence of herpes virus particles.MCMV DNA and glycoprotein B were demonstrated in the epithelial cells of the lung tissue in those animals by in situ hybridization and immunohistochemistry, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Anhui Medical University, Hefei, Anhui 230032, China.

ABSTRACT
We investigated the effect of murine cytomegalovirus (MCMV) on interstitial pneumonia in transplant recipients in an experimental skin allograft model. Skin transplantation between C57BL/6J and BALB/c mice was performed in the presence or absence of cyclosporin A treatment. Flow cytometry showed that the number of CD4(+) and CD8(+) cells and the level of IFN- γ decreased significantly in the groups treated with cyclosporin A. We either mock-infected or infected the mice with MCMV by intranasal administration and monitored pathophysiological behavior and body weight. The infected mice were sacrificed at different days postinfection for histology, immunohistochemistry, and molecular biological evaluations. Interstitial pneumonitis was observed in positive control groups as well as in experimental group that received cyclosporin A, a skin transplant, and infected with the highest dose of virus (10(5) PFU). Transmission electronic microscopy demonstrated the presence of herpes virus particles. MCMV DNA and glycoprotein B were demonstrated in the epithelial cells of the lung tissue in those animals by in situ hybridization and immunohistochemistry, respectively. Our data demonstrated the establishment of a mouse model of interstitial pneumonitis via MCMV infection after allogeneic skin transplantation.

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(a)–(c) H&E staining of lung tissue from infected or mock-infected mice. (a) Tissue from Group E (the mock-infected group) showed the normal histology of the mouse lung. (b)-(c) Tissues from Group D (b) 14 or (c) 21 days postinfection show mononuclear cell infiltration and edema of alveolar epithelia (arrows). (d)–(f) In situ hybridization with MCMV-specific probes showed that MCMV DNA was present in epithelial cells (arrows) of the alveoli in the lung tissue of mice (e) 14 or (f) 21 days postinfection, but not in (d) mock-infected mice. (g)–(i) Immunohistochemical staining using anti-MCMV gB monoclonal antibodies revealed viral protein gB (yellow-brown color, indicated by arrows) appeared in the alveolar epithelia (h) 14 and (i) 21 days postinfection. (g) We observed no staining in the lung tissue of mock-infected mice. Bar = 50 μm.
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fig7: (a)–(c) H&E staining of lung tissue from infected or mock-infected mice. (a) Tissue from Group E (the mock-infected group) showed the normal histology of the mouse lung. (b)-(c) Tissues from Group D (b) 14 or (c) 21 days postinfection show mononuclear cell infiltration and edema of alveolar epithelia (arrows). (d)–(f) In situ hybridization with MCMV-specific probes showed that MCMV DNA was present in epithelial cells (arrows) of the alveoli in the lung tissue of mice (e) 14 or (f) 21 days postinfection, but not in (d) mock-infected mice. (g)–(i) Immunohistochemical staining using anti-MCMV gB monoclonal antibodies revealed viral protein gB (yellow-brown color, indicated by arrows) appeared in the alveolar epithelia (h) 14 and (i) 21 days postinfection. (g) We observed no staining in the lung tissue of mock-infected mice. Bar = 50 μm.

Mentions: In order to confirm that the mouse model was a useful model of MCMV interstitial pneumonia, histological analysis was carried out on tissues from infected and mock-infected mice. Lung tissues from mice of the MCMV-infected control groups (Controls AV, BV, and CV) were markedly impaired, as evidenced by the dense inflammatory foci, compared with those from the negative control groups (Controls A, B, and C). The same pathological appearance was observed in Group C and Group D, which was different compared with Group E. The most severe abnormality appeared 14 days after infection. The inflammatory foci diffused through the lung parenchyma. The walls of the pulmonary alveoli had thickened, likely due to the edema of alveolar epithelia, proliferation of interstitial cells and interstitial lymphocytes, and inflammatory infiltration of mononuclear cells. In addition, the alveolar space became smaller, and the compensatory emphysema was found on the lobe edges. No abnormalities were noted in the lungs of uninfected Group E mice. Histological scoring indicated that the lungs of infected mice had significant interstitial inflammation (Figure 7).


A mouse model of interstitial pneumonitis induced by murine cytomegalovirus infection after allogeneic skin transplantation.

Ni D, Yu H, Zhang W, Gan L, Zhao J, Wang M, Chen J - Biomed Res Int (2013)

(a)–(c) H&E staining of lung tissue from infected or mock-infected mice. (a) Tissue from Group E (the mock-infected group) showed the normal histology of the mouse lung. (b)-(c) Tissues from Group D (b) 14 or (c) 21 days postinfection show mononuclear cell infiltration and edema of alveolar epithelia (arrows). (d)–(f) In situ hybridization with MCMV-specific probes showed that MCMV DNA was present in epithelial cells (arrows) of the alveoli in the lung tissue of mice (e) 14 or (f) 21 days postinfection, but not in (d) mock-infected mice. (g)–(i) Immunohistochemical staining using anti-MCMV gB monoclonal antibodies revealed viral protein gB (yellow-brown color, indicated by arrows) appeared in the alveolar epithelia (h) 14 and (i) 21 days postinfection. (g) We observed no staining in the lung tissue of mock-infected mice. Bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig7: (a)–(c) H&E staining of lung tissue from infected or mock-infected mice. (a) Tissue from Group E (the mock-infected group) showed the normal histology of the mouse lung. (b)-(c) Tissues from Group D (b) 14 or (c) 21 days postinfection show mononuclear cell infiltration and edema of alveolar epithelia (arrows). (d)–(f) In situ hybridization with MCMV-specific probes showed that MCMV DNA was present in epithelial cells (arrows) of the alveoli in the lung tissue of mice (e) 14 or (f) 21 days postinfection, but not in (d) mock-infected mice. (g)–(i) Immunohistochemical staining using anti-MCMV gB monoclonal antibodies revealed viral protein gB (yellow-brown color, indicated by arrows) appeared in the alveolar epithelia (h) 14 and (i) 21 days postinfection. (g) We observed no staining in the lung tissue of mock-infected mice. Bar = 50 μm.
Mentions: In order to confirm that the mouse model was a useful model of MCMV interstitial pneumonia, histological analysis was carried out on tissues from infected and mock-infected mice. Lung tissues from mice of the MCMV-infected control groups (Controls AV, BV, and CV) were markedly impaired, as evidenced by the dense inflammatory foci, compared with those from the negative control groups (Controls A, B, and C). The same pathological appearance was observed in Group C and Group D, which was different compared with Group E. The most severe abnormality appeared 14 days after infection. The inflammatory foci diffused through the lung parenchyma. The walls of the pulmonary alveoli had thickened, likely due to the edema of alveolar epithelia, proliferation of interstitial cells and interstitial lymphocytes, and inflammatory infiltration of mononuclear cells. In addition, the alveolar space became smaller, and the compensatory emphysema was found on the lobe edges. No abnormalities were noted in the lungs of uninfected Group E mice. Histological scoring indicated that the lungs of infected mice had significant interstitial inflammation (Figure 7).

Bottom Line: Flow cytometry showed that the number of CD4(+) and CD8(+) cells and the level of IFN- γ decreased significantly in the groups treated with cyclosporin A.Transmission electronic microscopy demonstrated the presence of herpes virus particles.MCMV DNA and glycoprotein B were demonstrated in the epithelial cells of the lung tissue in those animals by in situ hybridization and immunohistochemistry, respectively.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Anhui Medical University, Hefei, Anhui 230032, China.

ABSTRACT
We investigated the effect of murine cytomegalovirus (MCMV) on interstitial pneumonia in transplant recipients in an experimental skin allograft model. Skin transplantation between C57BL/6J and BALB/c mice was performed in the presence or absence of cyclosporin A treatment. Flow cytometry showed that the number of CD4(+) and CD8(+) cells and the level of IFN- γ decreased significantly in the groups treated with cyclosporin A. We either mock-infected or infected the mice with MCMV by intranasal administration and monitored pathophysiological behavior and body weight. The infected mice were sacrificed at different days postinfection for histology, immunohistochemistry, and molecular biological evaluations. Interstitial pneumonitis was observed in positive control groups as well as in experimental group that received cyclosporin A, a skin transplant, and infected with the highest dose of virus (10(5) PFU). Transmission electronic microscopy demonstrated the presence of herpes virus particles. MCMV DNA and glycoprotein B were demonstrated in the epithelial cells of the lung tissue in those animals by in situ hybridization and immunohistochemistry, respectively. Our data demonstrated the establishment of a mouse model of interstitial pneumonitis via MCMV infection after allogeneic skin transplantation.

Show MeSH
Related in: MedlinePlus