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Effect of secondhand smoke on pulmonary t cell recruitment

Institution: University of California, Davis
Investigator(s): Lisa Miller, Ph.D.
Award Cycle: 1999 (Cycle 8) Grant #: 8IT-0054 Award: $69,094
Subject Area: Pulmonary Disease
Award Type: Inno Dev & Exp Awards (IDEAS)
Abstracts

Initial Award Abstract
The role of tobacco smoke as a primary risk factor for chronic inflammatory lung disease in humans is well recognized. Although the mechanisms by which chemical constituents of tobacco smoke promote inflammatory processes is not well defined, accumulation of white blood cells (leukocytes) within airways is consistently observed in the lungs of smokers. Perpetuation of such an inflammatory response can disrupt lung function. Clinically, increased numbers of a specific inflammatory cell type, T lymphocytes, within the lung are a hallmark of chronic lung inflammation. T lymphocytes play a central role in chronic inflammatory processes by responding to foreign matter (antigens). In order to accumulate within the airways, T lymphocytes must migrate across a barrier of surface-lining cells (i.e., lung epithelium). It is likely that the epithelium lining the large airways plays an important role in modulating inflammatory responses, as the cells of this location are first to encounter injurious agents and inhaled antigens. The objective of this project is to determine if environmental (second-hand) tobacco smoke can promote inflammation within the lung by enhancing airway epithelial cells to make proteins which attract T lymphocytes. There are two specific aims: (1) to study the effect of environmental tobacco smoke on lung proteins which attract T lymphocytes; and (2) to characterize the effect of environmental tobacco smoke on the specific type of T lymphocyte which accumulates within the lung. Although the health hazards of mainstream tobacco smoke are well known, epidemiological studies suggest that environmental tobacco smoke can also impact on the health of nonsmokers. Completion of the studies proposed in this application will define one potential mechanism by which environmental tobacco smoke may have a pro-inflammatory effect within the lung.

Final Report
The role of tobacco smoke as a primary risk factor for chronic inflammatory lung disease in humans is well recognized. Although the mechanisms by which chemical constituents of tobacco smoke promote inflammatory processes is not well defined, leukocyte accumulation within the airways is a consistent clinical observation. Persistent mobilization of inflammatory cells into the airways and perpetuation of the inflammatory response can lead the disruption of lung function. Histologically, increased numbers of T lymphocytes within the lung are a hallmark of chronic lung inflammation. T lymphocytes play a central role in chronic inflammatory processes by responding to foreign antigen exposure. In order to accumulate within the airways, T lymphocytes must migrate across a barrier of epithelium. It is likely that the epithelium lining the large airways is functionally important in an inflammatory response, as the cells of this location are first to encounter injurious agents and inhaled antigens. The objective of this application was to determine if environmental (“second-hand”) tobacco smoke can promote inflammation within the lung by enhancing airway epithelial cell production of proteins that attract T lymphocytes. The objective of this application was addressed by completing the following two specific aims: (1) characterization of the effect of environmental tobacco smoke on proteins within the lung that attract T lymphocytes; and (2) characterization of the effect of environmental tobacco smoke on the type of T lymphocyte that accumulates within the lung. Findings using a rodent model indicate that exposure to environmental tobacco smoke for three weeks resulted in an overall increase in lymphocytes and dendritic cells within airways. In conjunction with these findings, we have characterized airways for expression of proteins that attract this unique subpopulation of lymphocytes. Although the health hazards of mainstream tobacco smoke are well known, epidemiological studies suggest that environmental tobacco smoke can also impact on the health of nonsmokers. Completion of the studies proposed in this application has defined one potential mechanism by which inhalation of environmental tobacco smoke may promote chronic inflammation within the lung.
Publications

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

Expression of the beta 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

House dust mite-sensitized rhesus monkeys exhibit time dependent local and systemic activation of lymphocites
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 RL, 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 DM, 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 DM 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 ABS
Yr: 2001 Vol: 163 Nbr: 5 Abs: A433 Pg: