Effects of tobacco on inflammatory cell responses
Abstracts
Initial Award Abstract |
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The role of inflammation in promoting and perpetuating pulmonary disease states is profound. Indeed, the rate of morbidity and mortality ensued by chronic inflammatory conditions such as chronic obstructive pulmonary disease (COPD) outweighs that which results from lung cancer. Cigarette smoke is a common etiologic factor in chronic bronchitis and COPD, suggesting that the chemical components of tobacco have a specific effect on the cellular constituents of the lung. Although chronic bronchitis and airway obstruction appear to be discrete syndromes, histologic and clinical evidence implicate the inflammatory response as a common path. The overall goal of this project is to characterize the biology of white blood cell recruitment to the lung in response to tobacco smoke. In this proposal, we will test the hypothesis that exposure of pulmonary airways to tobacco smoke components can stimulate the production of proteins which specifically recruit white blood cells (leukocytes) into the lung. We will use a cell culture model to allow focused attention on the precise biochemical and molecular mechanisms of leukocyte movement into the lung. A clear understanding of the basic mechanisms by which leukocytes recirculate within the lung is imperative for the development of therapeutic treatments which specifically target the immunologic response to tobacco smoke exposure. |
Final Report |
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The objective of this project was to understand the biology of inflammatory cell recruitment to the lung in response to tobacco smoke. This project has tested the hypothesis that exposure of airway epithelial cells to tobacco smoke components can stimulate production of proteins (chemokines) that specifically bring inflammatory cells into the lung. The specific aims of this project were the following: (1) determine the effect of human bronchial epithelium exposure to tobacco smoke on subsequent inflammatory cell migration; (2) characterize expression of chemokines by bronchial epithelium in response to tobacco smoke; (3) determine the role of chemokines on inflammatory cell migration across bronchial epithelium and (4) characterize functional changes on migrated inflammatory cells by immunological markers. Work to date has focused on the functional role of chemokine expression by human airway epithelium, particularly in the trafficking of inflammatory cells. The direct effect of environmental tobacco smoke (ETS), or “second-hand smoke” on the expression of chemokines by airway epithelial cells was examined by in vitro methodology. In addition, the effects of acrolein and acetaldehyde exposure (volatile components of ETS) were examined using this approach. ETS was simulated by extracts collected from aged and diluted sidestream cigarette smoke and added directly to human airway epithelial cell cultures. Following an overnight exposure to either ETS or acrolein/acetaldehyde, culture supernatants and RNA were collected for cellular and molecular analysis. Using functional assays for chemokines, we have found that ETS and acrolein/acetaldehyde induced the migration of inflammatory cells to culture supernatants. Further, ETS and acrolein/acetaldehyde-treated cultures expressed higher levels of chemokine messenger RNA . Cumulatively, these findings suggest that exposure of the airways to volatile components of ETS result in the enhanced expression of chemokines in the lung; this suggests a putative mechanism by which persistent inhalation of “second-hand smoke” can result in airway inflammation and chronic lung disease. |
Publications
| Expression of the HML-1 epitope on human monocytes is independent of alphaE integrin mRNA |
| Periodical: Inflammation |
Index Medicus: |
| Authors: Miller LA, Li C, Hyde DM |
ART |
| Yr: 2000 |
Vol: 24 |
Nbr: |
Abs: |
Pg: 195-205 |
| Trafficking of neutrophils across airway epithelium is dependent upon both thioredoxin- and pertussis toxin-sensitive signaling mechanisms |
| Periodical: Journal of Leukocyte Biology |
Index Medicus: |
| Authors: Miller LA, Usachenko JL, McDonald RJ, Hyde DM |
ART |
| Yr: 2000 |
Vol: 68 |
Nbr: |
Abs: |
Pg: 201-208 |
| Neutrophils accelerate clearance of necrotic epithelial cells following ozone-induced lung injury in rhesus monkeys |
| Periodical: American Journal of Physiology |
Index Medicus: |
| Authors: Hyde DM, Miller LA, McDonald RJ, et al |
ART |
| Yr: 1999 |
Vol: 277 |
Nbr: |
Abs: |
Pg: L1190-L1198 |
| Expression of the beta6 integrin subunit is associated with sites of neutrophil influx within ozone-exposed airways |
| Periodical: Journal of Histochemistry and Cytochemistry |
Index Medicus: |
| Authors: Miller LA, Barnett NL, Sheppard D, Hyde DM |
ART |
| Yr: 2001 |
Vol: 49 |
Nbr: 1 |
Abs: |
Pg: 41-47 |
| Monocyte chemokine expression by airway epithelium is enhanced following exposure to environmental tobacco smoke |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Li C, Pinkerton KE, Hyde DM |
ABS |
| Yr: 1999 |
Vol: 159 |
Nbr: 3 |
Abs: A510 |
Pg: |
| House dust mite-sensitized rhesus monkeys exhibit time dependent local and systemic activation of lymphocytes |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Gerriets JE, Hyde DM |
ABS |
| Yr: 2000 |
Vol: 161 |
Nbr: 3 |
Abs: A206 |
Pg: |
| Correlation of cytokine/chemokine expression with immune cell recruitment by airway generation in house dust mite-sensitized rhesus monkeys |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Hurst SD, Coffman L, et al |
ABS |
| Yr: 2000 |
Vol: 161 |
Nbr: 3 |
Abs: A836 |
Pg: |
| Neonatal pulmonary immune responses following episodic exposure to aerosolized house dust mite |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Plopper CG, Hyde JE, et al |
ABS |
| Yr: 2001 |
Vol: 163 |
Nbr: 5 |
Abs: A601 |
Pg: |
| Chemokine expression and accumulation of dendritic cells following exposure to environmental tobacco smoke |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Gurley E, Wang B, Gershwin LJ, Pinkerton KE, Hyde DM |
ABS |
| Yr: 2001 |
Vol: 163 |
Nbr: 5 |
Abs: A177 |
Pg: |
| Characterization of IL-4 and macrophage derived-chemokine expression in airways of house dust mite-sensitized rhesus monkeys |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Chou DL, Hyde DM, Hurst SD, Coffman RL, Gershwin LJ, Miller LA |
ABS |
| Yr: 2001 |
Vol: 163 |
Nbr: 5 |
Abs: A868 |
Pg: |
| local and systemic immune responses in neonatal house dust mite-sensitized rhesus monkeys following episodic exposure to ozone |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Gerriets JE, Miller LA, Gershwin LJ, Hyde DMM |
ABS |
| Yr: 2001 |
Vol: 163 |
Nbr: 5 |
Abs: A601 |
Pg: |
| Localization of immune cells in neonatal house dust mite-sensitized rhesus monkeys following episodic exposure to ozone |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Putney LF, Stovall MY, et al |
ABS |
| Yr: 2001 |
Vol: 163 |
Nbr: 5 |
Abs: A433 |
Pg: |
| Expression of the HML-1 epitope on human monocytes is independent of alphaE integrin mRNA |
| Periodical: Inflammation |
Index Medicus: |
| Authors: Miller LA, Li C, Hyde DM |
ART |
| Yr: 2000 |
Vol: 24 |
Nbr: |
Abs: |
Pg: 195-205 |
| Trafficking of neutrophils across airway epithelium is dependent upon both thioredoxin- and pertussis toxin-sensitive signaling mechanisms |
| Periodical: Journal of Leukocyte Biology |
Index Medicus: |
| Authors: Miller LA, Usachenko JL, McDonald RJ, Hyde DM |
ART |
| Yr: 2000 |
Vol: 68 |
Nbr: |
Abs: |
Pg: 201-208 |
| Neutrophils accelerate clearance of necrotic epithelial cells following ozone-induced lung injury in rhesus monkeys |
| Periodical: American Journal of Physiology |
Index Medicus: |
| Authors: Hyde DM, Miller LA, McDonald RJ, et al |
ART |
| Yr: 1999 |
Vol: 277 |
Nbr: |
Abs: |
Pg: L1190-L1198 |
| Expression of the beta6 integrin subunit is associated with sites of neutrophil influx within ozone-exposed airways |
| Periodical: Journal of Histochemistry and Cytochemistry |
Index Medicus: |
| Authors: Miller LA, Barnett NL, Sheppard D, Hyde DM |
ART |
| Yr: 2001 |
Vol: 49 |
Nbr: 1 |
Abs: |
Pg: 41-47 |
| Monocyte chemokine expression by airway epithelium is enhanced following exposure to environmental tobacco smoke |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Li C, Pinkerton KE, Hyde DM |
ABS |
| Yr: 1999 |
Vol: 159 |
Nbr: 3 |
Abs: A510 |
Pg: |
| House dust mite-sensitized rhesus monkeys exhibit time dependent local and systemic activation of lymphocytes |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Gerriets JE, Hyde DM |
ABS |
| Yr: 2000 |
Vol: 161 |
Nbr: 3 |
Abs: A206 |
Pg: |
| Correlation of cytokine/chemokine expression with immune cell recruitment by airway generation in house dust mite-sensitized rhesus monkeys |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Hurst SD, Coffman L, et al |
ABS |
| Yr: 2000 |
Vol: 161 |
Nbr: 3 |
Abs: A836 |
Pg: |
| Neonatal pulmonary immune responses following episodic exposure to aerosolized house dust mite |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Plopper CG, Hyde JE, et al |
ABS |
| Yr: 2001 |
Vol: 163 |
Nbr: 5 |
Abs: A601 |
Pg: |
| Chemokine expression and accumulation of dendritic cells following exposure to environmental tobacco smoke |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Gurley E, Wang B, Gershwin LJ, Pinkerton KE, Hyde DM |
ABS |
| Yr: 2001 |
Vol: 163 |
Nbr: 5 |
Abs: A177 |
Pg: |
| Characterization of IL-4 and macrophage derived-chemokine expression in airways of house dust mite-sensitized rhesus monkeys |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Chou DL, Hyde DM, Hurst SD, Coffman RL, Gershwin LJ, Miller LA |
ABS |
| Yr: 2001 |
Vol: 163 |
Nbr: 5 |
Abs: A868 |
Pg: |
| local and systemic immune responses in neonatal house dust mite-sensitized rhesus monkeys following episodic exposure to ozone |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Gerriets JE, Miller LA, Gershwin LJ, Hyde DMM |
ABS |
| Yr: 2001 |
Vol: 163 |
Nbr: 5 |
Abs: A601 |
Pg: |
| Localization of immune cells in neonatal house dust mite-sensitized rhesus monkeys following episodic exposure to ozone |
| Periodical: American Journal of Respiratory and Critical Care Medicine |
Index Medicus: |
| Authors: Miller LA, Putney LF, Stovall MY, et al |
ABS |
| Yr: 2001 |
Vol: 163 |
Nbr: 5 |
Abs: A433 |
Pg: |
