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Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin.

Yamauchi K, Kasuya Y, Kuroda F, Tanaka K, Tsuyusaki J, Ishizaki S, Matsunaga H, Iwamura C, Nakayama T, Tatsumi K - Respir. Res. (2011)

Bottom Line: Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases.Lung inflammation in the acute phase (7 dpi) was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid.In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.

ABSTRACT

Background: Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM)-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT) and CD69-deficient (CD69-/-) mice.

Methods: The mice received a single dose of 3 mg/kg body weight of BLM and were sacrificed at 7 or 14 days post-instillation (dpi). Lung inflammation in the acute phase (7 dpi) was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid. In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays. We also used reverse transcription polymerase chain reaction to measure the mRNA expression level of transforming growth factor β1 (TGF-β1) in the lungs of BLM-treated mice.

Results: CD69-/- mice exhibited less lung damage than WT mice, as shown by reductions in the following indices: (1) loss of body weight, (2) wet/dry ratio of lung, (3) cytokine levels in BALF, (4) histological evidence of lung injury, (5) lung collagen deposition, and (6) TGF-β1 mRNA expression in the lung.

Conclusion: The present study clearly demonstrates that CD69 plays an important role in the progression of lung injury induced by BLM.

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Effect of bleomycin on the lung architecture in wild-type and CD69-deficient mice. Comparison of the lung architecture in WT and CD69-/- mice after instillation of BLM or PBS (sham treatment), as shown by hematoxylin-eosin (A) and Masson's trichrome (B) staining of representative tissue sections.
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Figure 5: Effect of bleomycin on the lung architecture in wild-type and CD69-deficient mice. Comparison of the lung architecture in WT and CD69-/- mice after instillation of BLM or PBS (sham treatment), as shown by hematoxylin-eosin (A) and Masson's trichrome (B) staining of representative tissue sections.

Mentions: For investigating the effects of CD69 deficiency on BLM-induced lung fibrosis, the histopathological changes in the lung were evaluated at 14 dpi. Representative microscopic findings following H-E or Masson's trichrome staining of the lung sections are shown in Figure 5. The lung architecture was nearly normal between the two genotypes injected with PBS. However, the WT lung tissue exposed to BLM showed a strong accumulation of inflammatory cells, thickening of the alveolar walls, and fibrotic lesions. Although these findings were also observed in the CD69-/- mice, the extent and intensity were much less than those in the WT mice. The severity of the fibrosis was also assessed by Ashcroft scoring. This assessment confirmed that the severity of fibrosis was significantly reduced in BLM-treated CD69-/- mice relative to that in the correspondingly injured WT mice (Figure 6A). In accordance with the results of the Ashcroft scoring, collagen deposition was markedly developed in the lungs of BLM-treated WT mice at 14 dpi compared to that in the sham group. Moreover, the increased collagen contents induced by BLM were significantly attenuated in CD69-/- mice (Figure 6B). TGF-β1 mRNA expression in the lung tissue was measured by RT-PCR at 7 dpi. The BLM-induced expression of TGF-ß1 was strongly reduced in CD69-/- mice relative to that in WT mice (Figure 6C).


Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin.

Yamauchi K, Kasuya Y, Kuroda F, Tanaka K, Tsuyusaki J, Ishizaki S, Matsunaga H, Iwamura C, Nakayama T, Tatsumi K - Respir. Res. (2011)

Effect of bleomycin on the lung architecture in wild-type and CD69-deficient mice. Comparison of the lung architecture in WT and CD69-/- mice after instillation of BLM or PBS (sham treatment), as shown by hematoxylin-eosin (A) and Masson's trichrome (B) staining of representative tissue sections.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198935&req=5

Figure 5: Effect of bleomycin on the lung architecture in wild-type and CD69-deficient mice. Comparison of the lung architecture in WT and CD69-/- mice after instillation of BLM or PBS (sham treatment), as shown by hematoxylin-eosin (A) and Masson's trichrome (B) staining of representative tissue sections.
Mentions: For investigating the effects of CD69 deficiency on BLM-induced lung fibrosis, the histopathological changes in the lung were evaluated at 14 dpi. Representative microscopic findings following H-E or Masson's trichrome staining of the lung sections are shown in Figure 5. The lung architecture was nearly normal between the two genotypes injected with PBS. However, the WT lung tissue exposed to BLM showed a strong accumulation of inflammatory cells, thickening of the alveolar walls, and fibrotic lesions. Although these findings were also observed in the CD69-/- mice, the extent and intensity were much less than those in the WT mice. The severity of the fibrosis was also assessed by Ashcroft scoring. This assessment confirmed that the severity of fibrosis was significantly reduced in BLM-treated CD69-/- mice relative to that in the correspondingly injured WT mice (Figure 6A). In accordance with the results of the Ashcroft scoring, collagen deposition was markedly developed in the lungs of BLM-treated WT mice at 14 dpi compared to that in the sham group. Moreover, the increased collagen contents induced by BLM were significantly attenuated in CD69-/- mice (Figure 6B). TGF-β1 mRNA expression in the lung tissue was measured by RT-PCR at 7 dpi. The BLM-induced expression of TGF-ß1 was strongly reduced in CD69-/- mice relative to that in WT mice (Figure 6C).

Bottom Line: Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases.Lung inflammation in the acute phase (7 dpi) was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid.In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.

ABSTRACT

Background: Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM)-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT) and CD69-deficient (CD69-/-) mice.

Methods: The mice received a single dose of 3 mg/kg body weight of BLM and were sacrificed at 7 or 14 days post-instillation (dpi). Lung inflammation in the acute phase (7 dpi) was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid. In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays. We also used reverse transcription polymerase chain reaction to measure the mRNA expression level of transforming growth factor β1 (TGF-β1) in the lungs of BLM-treated mice.

Results: CD69-/- mice exhibited less lung damage than WT mice, as shown by reductions in the following indices: (1) loss of body weight, (2) wet/dry ratio of lung, (3) cytokine levels in BALF, (4) histological evidence of lung injury, (5) lung collagen deposition, and (6) TGF-β1 mRNA expression in the lung.

Conclusion: The present study clearly demonstrates that CD69 plays an important role in the progression of lung injury induced by BLM.

Show MeSH
Related in: MedlinePlus