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I. Differential gene expression in human peripheral blood monocytes and alveolar macrophages II. Macrophage colony-stimulating factor is important in the development of pulmonary fibrosis

Opalek, Judy Marcus
http://rave.ohiolink.edu/etdc/view?acc_num=osu1075754091

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Pathology.
Monocytes are precursors to tissue macrophages. We performed microarray expression analysis to determine the genetic expression profiles of peripheral blood monocytes (PBM) and alveolar macrophages (AM). Our data indicates that several hundred genes are differentially regulated in PBM and AM. These include genes involved in cellular scavenging, intracellular signaling pathways, cellular survival and/or differentiation. We observed that the chemokine receptor expression profiles of PBM and AM differed in the gene array analysis, and confirmed these results by reverse transcriptase polymerase chain reaction, flow cytometry and functional analyses. Our data indicates that circulating monocytes express the chemokine receptors CCR1 and CCR2, and that monocytes functionally respond by migrating toward both MCP-1 and MIP-1a. In contrast, alveolar macrophages do not express CCR1 or CCR2, but do express the MIP-1a chemokine receptor CCR5. AM did not respond to MCP-1 but did respond to MIP-1a in a migration assay. The addition of an anti-CCR5 blocking antibody completely abrogated MIP-1a-induced migration in AM, but did not affect monocytes. These data may be helpful in understanding the regulated recruitment of inflammatory cells in areas of lung inflammation. This data is relevant to human disease, as in pulmonary fibrosis (PF) high concentrations of MCP-1 are found in the lung lavage fluid from affected patients but not in normal volunteers. PF is a serious lung disease characterized by progressive scarring of the lung tissue, eventually leading to hypoxemia and death. Prognosis is worsened in patients with more monocytes and macrophages in their lungs. We used an animal model of bleomycin-induced PF to examine the role of Macrophage Colony-Stimulating Factor (M-CSF) in the development of this disease. We chose this model because mice that are genetically deficient in M-CSF have decreased numbers of circulating monocytes and tissue macrophages, and provide a useful model for studying the role of these cells and this growth factor. Mice lacking M-CSF survived better, lost less weight and developed less fibrosis than their M-CSF normal littermates when treated with systemic bleomycin. These data clearly implicate M-CSF-responsive monocytes and tissue macrophages in the development of pulmonary fibrosis.
Clay Marsh (Advisor)
129 p.
monocyte(s); alveolar macrophage(s); microarray analysis; MCP-1/CCR2; MIP-1a/CCR1, CCR5; M-CSF; bleomycin; pulmonary fibrosis

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Citations

  • Opalek, J. M. (2004). I. Differential gene expression in human peripheral blood monocytes and alveolar macrophages II. Macrophage colony-stimulating factor is important in the development of pulmonary fibrosis [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1075754091

    APA Style (7th edition)

  • Opalek, Judy. I. Differential gene expression in human peripheral blood monocytes and alveolar macrophages II. Macrophage colony-stimulating factor is important in the development of pulmonary fibrosis. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1075754091.

    MLA Style (8th edition)

  • Opalek, Judy. "I. Differential gene expression in human peripheral blood monocytes and alveolar macrophages II. Macrophage colony-stimulating factor is important in the development of pulmonary fibrosis." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1075754091

    Chicago Manual of Style (17th edition)

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© 2004, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.