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Detection of Experimentally Induced Pulmonary Granuloma Inflammation in Monocyte Chemoattractant Protein-1 Reporter Mice

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Abstract

Purpose

Among different chemokines, monocyte chemoattractant protein-1 (MCP-1) plays an important role in inflammatory disorders of lung. In response to stimuli, MCP-1 increases its transcription as an immediate early gene. In this paper, we describe the MCP-1–enhanced green fluorescent protein(EGFP) transgenic mouse in which EGFP expression is driven by human MCP-1 promoter and mimics the MCP-1 expression in situ. Thus, the MCP-1 reporter mouse model is designed to facilitate a better understanding of its role in various diseases. We employed this mouse model in a pulmonary granulomatous inflammation model using intratracheal instillation of Sephadex (SDX) beads and compared the EGFP reporter expression to endogenous MCP-1 expression through the course of inflammation.

Procedures

We analyzed the temporal pattern of SDX-induced infiltration of inflammatory cells in lung and in bronchoalveolar lavage fluid (BALF). The changes in tissue fluorescence, gene, and protein expressions for both MCP-1 and EGFP were analyzed.

Results

SDX instillation caused massive infiltration of inflammatory cells in BALF and lung tissue at the end of day 3. There was an increase of fluorescence in SDX-treated lung and BALF cells. By using lipopolysaccharide-induced systemic inflammation model, increase of fluorescence was found in bone marrow Gr-1(+) cells with high Mac-1 expression. MCP-1 and EGFP gene expression and MCP-1 protein level were increased after day 1, peaked at day 3, and declined toward basal levels at day 5. In contrast, EGFP protein level peaked after day 3 and remained elevated after day 5. Immunohistochemical staining revealed the MCP-1 and EGFP expression primarily at alveolar macrophages, macrophages infiltrating the granulomatous lesions and in bronchiolar epithelial cells.

Conclusions

By using a pulmonary granuloma model, we showed that EGFP transgene reporter expression in MCP-1-EGFP mouse was correlated to the endogenous MCP-1 induction. The establishment of this mouse model will provide a valuable tool for monitoring the activation of monocytes/macrophages and facilitate the studies on the roles of MCP-1 gene in various inflammatory diseases.

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Acknowledgments

The authors gratefully thank the technical assistance provided by Shan-Wen Liu, Hsiao-Chi Yu, and Tzu-Chin Wu. This research was supported by NHRI intramural research grants ME097-PP02, NM097-PP06, and ME097-SP07. Taiwan National Science Council grants NSC-96-2627-B-400-001. Subbiah Rajasekaran was supported by NHRI postdoctoral fellowships.

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Authors and Affiliations

  1. Division of Medical Engineering Research, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan, Republic of China

    Subbiah Rajasekaran, Mei-Ru Chen & Kurt Ming-Chao Lin

  2. Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, Republic of China

    Vivia Yu-Ying Kao

  3. Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan, Republic of China

    Alex Liang-Tung Yang

  4. Department of Biomedical Engineering and Environmental Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China

    Ching-Han Hsu

  5. Department of Radiology and Committee on Medical Physics, University of Chicago, Chicago, IL, USA

    Chin-Tu Chen

Authors
  1. Subbiah Rajasekaran
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  2. Vivia Yu-Ying Kao
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  3. Mei-Ru Chen
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  4. Alex Liang-Tung Yang
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  7. Kurt Ming-Chao Lin
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Corresponding author

Correspondence to Kurt Ming-Chao Lin.

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Rajasekaran, S., Kao, V.YY., Chen, MR. et al. Detection of Experimentally Induced Pulmonary Granuloma Inflammation in Monocyte Chemoattractant Protein-1 Reporter Mice. Mol Imaging Biol 12, 163–173 (2010). https://doi.org/10.1007/s11307-009-0261-9

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  • DOI: https://doi.org/10.1007/s11307-009-0261-9

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