國家衛生研究院 NHRI:Item 3990099045/3922

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Title:	Detection of experimentally induced pulmonary granuloma Inflammation in monocyte chemoattractant protein-1 reporter mice
Authors:	Rajasekaran, S;Kao, VY;Chen, MR;Yang, AL;Hsu, CH;Chen, CT;Lin, KM
Contributors:	Division of Medical Engineering Research;Institute of Cellular and Systems Medicine
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.
Date:	2010-04
Relation:	Molecular Imaging and Biology. 2010 Apr;12(2):163-173.
Link to:	http://dx.doi.org/10.1007/s11307-009-0261-9
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1536-1632&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000275974900006
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77953534372
Appears in Collections:	[Kurt Ming-Chao Lin] Periodical Articles [Liang-Tung Yang] Periodical Articles

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