PMID- 19806405 OWN - NLM STAT- MEDLINE DCOM- 20100629 LR - 20211020 IS - 1860-2002 (Electronic) IS - 1536-1632 (Linking) VI - 12 IP - 2 DP - 2010 Apr TI - Detection of experimentally induced pulmonary granuloma inflammation in monocyte chemoattractant protein-1 reporter mice. PG - 163-73 LID - 10.1007/s11307-009-0261-9 [doi] AB - 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. FAU - Rajasekaran, Subbiah AU - Rajasekaran S AD - Division of Medical Engineering Research, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan, Republic of China. FAU - Kao, Vivia Yu-Ying AU - Kao VY FAU - Chen, Mei-Ru AU - Chen MR FAU - Yang, Alex Liang-Tung AU - Yang AL FAU - Hsu, Ching-Han AU - Hsu CH FAU - Chen, Chin-Tu AU - Chen CT FAU - Lin, Kurt Ming-Chao AU - Lin KM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091006 PL - United States TA - Mol Imaging Biol JT - Molecular imaging and biology JID - 101125610 RN - 0 (Chemokine CCL2) RN - 0 (Lipopolysaccharides) RN - 0 (enhanced green fluorescent protein) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Animals MH - Bronchoalveolar Lavage Fluid/cytology MH - Chemokine CCL2/*genetics/metabolism MH - Disease Models, Animal MH - Flow Cytometry MH - Genes, Reporter/*genetics MH - Genetic Vectors/genetics MH - Genotype MH - Granuloma, Respiratory Tract/chemically induced/*complications/*diagnosis MH - Green Fluorescent Proteins/genetics/metabolism MH - Humans MH - Immunohistochemistry MH - Leukocyte Count MH - Lipopolysaccharides/pharmacology MH - Lung/drug effects/metabolism/pathology MH - Mice MH - Mice, Transgenic MH - Molecular Imaging MH - Pneumonia/chemically induced/*complications/*diagnosis EDAT- 2009/10/07 06:00 MHDA- 2010/06/30 06:00 CRDT- 2009/10/07 06:00 PHST- 2009/01/26 00:00 [received] PHST- 2009/04/28 00:00 [accepted] PHST- 2009/04/01 00:00 [revised] PHST- 2009/10/07 06:00 [entrez] PHST- 2009/10/07 06:00 [pubmed] PHST- 2010/06/30 06:00 [medline] AID - 10.1007/s11307-009-0261-9 [doi] PST - ppublish SO - Mol Imaging Biol. 2010 Apr;12(2):163-73. doi: 10.1007/s11307-009-0261-9. Epub 2009 Oct 6.