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Allergen-Induced Chemokine Release from the Bronchial Epithelium: A Novel Lysosomal Release Mechanism

Webb, Mark
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1399276040

Abstract Details

2014, PhD, University of Cincinnati, Medicine: Immunology.
Asthma is a chronic inflammatory disease of the lung. In recent years, the airway epithelium has been identified as an important contributor to the initial development of asthma after allergen exposure. The mechanisms by which epithelial cells respond to allergen to help drive downstream inflammation and the initiation of an immune response are poorly understood. In this dissertation we sought to understand the basic mechanisms that control release of chemokines and cytokines in general and CCL20 in particular. To do this, we measured levels of CCL20 and other cell mediators retained in cells and released from cells, and we visualized these mediators' intracellular localization via immunofluorescence microscopy. We found that a number of chemokines and cytokines are stored within bronchial epithelial cells under homeostatic conditions. In addition, CCL20 was stored in lysosomes, and its release was partially mediated through secretion of these lysosomes. In order to determine the intracellular localization of multiple chemokines and cytokines simultaneously, we again employed fluorescence microscopy. We also developed a novel technique to measure specific proteins in subcellular organelles using modified flow cytometry. We found that lysosomes containing CCL20 are released after exposure to HDM. We also found that the secretory lysosomes containing CCL20 also appear to contain other chemokines and cytokines released in response to HDM. We also found that allergens other than HDM induce release of specific subsets of chemokines and cytokines. These studies demonstrate a complex storage and release mechanism for chemokines and cytokines of the bronchial epithelium. These findings improve our understanding of the initial interactions between allergen and the epithelium, and provide an interesting potential target for future treatments that will allow them to be both targeted and robust.
Marsha Wills-Karp, Ph.D. (Committee Chair)
Lee Denson, M.D. (Committee Member)
Simon Hogan, Ph.D. (Committee Member)
Marshall Montrose, Ph.D. (Committee Member)
Nives Zimmermann, Ph.D. (Committee Member)
237 p.
Immunology
asthma; chemokine; lysosome; CCL20; bronchial epithelium

Recommended Citations

Citations

  • Webb, M. (2014). Allergen-Induced Chemokine Release from the Bronchial Epithelium: A Novel Lysosomal Release Mechanism [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1399276040

    APA Style (7th edition)

  • Webb, Mark. Allergen-Induced Chemokine Release from the Bronchial Epithelium: A Novel Lysosomal Release Mechanism. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1399276040.

    MLA Style (8th edition)

  • Webb, Mark. "Allergen-Induced Chemokine Release from the Bronchial Epithelium: A Novel Lysosomal Release Mechanism." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1399276040

    Chicago Manual of Style (17th edition)

ucin1399276040
364
© 2014, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.