Effect of tobacco smoke on leukocyte adhesion in vivo
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Over 1 million individuals between the ages of 45 and 60 are currently on Social Security rolls as being partially or wholly disabled on the basis of chronic obstructive pulmonary disease (COPD) The most important etiological factor in COPD is airway inflammation that is particularly associated with exposure to tobacco smoke (TS) and the recruitment of leukocytes into the airways of the lungs. This relationship appears to strengthen with the number of cigarettes smoked and the amount of smoke inhaled (i.e., both mainstream smoking and exposure to secondhand smoke). At the cellular level, pulmonary inflammation is characterized by the inducement of circulating leukocytes (e.g., certain types of white blood cells) to migrate through the cell layer lining blood vessels in the lung (pulmonary endothelium) into the “extravascular” spaces of the lung. The molecular and cellular mechanisms mediating the interaction of circulating leukocytes with pulmonary endothelial cells in smokers are not well understood. It has been suggested that exposure to TS could result in activation of circulating leukocytes and result in their recruitment in the airways. Thus we hypothesize that the inhibition of the inflammatory recruitment process (and, in turn, the prevention of the migration of activated leukocytes into the airways of humans exposed to mainstream or secondhand TS) will result in attenuation of smoking-mediated tissue damage caused by pulmonary inflammation. By expressing chemical mediators and specific molecules necessary for adhesion, endothelial cells play a central role in the various steps involved in leukocyte recruitment. These steps include leukocyte “rolling”, adhesion to the endothelium, and transmigration to sites of inflammation in the airways. These critical steps of the recruitment process are mediated by distinct “adhesion receptors”. Although several of the receptors involved in mediating leukocyte adhesion under normal physiological conditions have been identified, how this process may be altered by exposure to TS (in mainstream and second hand smokers) has not been investigated.
 
 
 
 
 
 
 
 This project will apply the current knowledge of immunology, vascular and cell biology in understanding the cellular mechanisms that mediate leukocyte adhesion to pulmonary blood vessels. Leukocytes isolated from the peripheral blood of smokers (suffering from chronic bronchitis or asthmatic bronchitis) or non-smokers will be fluorescently labeled and the subsequent recruitment process will be closely observed using an animal model. Using state of the art microscopic techniques, it will be possible to visualize the interaction of circulating leukocytes (and any detrimental effects of TS) within pulmonary vessels. From the results obtained from these studies we hope to identify the specific receptors and adhesion molecules that contribute to leukocyte recruitment during episodes of chronic bronchitis or asthma that afflict smokers (and some individuals exposed to secondhand smoke). The knowledge derived from these studies will help in developing therapeutic strategies to mitigate TS-related pulmonary disease in humans.