Chronic bronchitis: pathology of mucin gene expression
Initial Award Abstract
Tobacco smoking causes a number of different lung diseases. Among these are the diseases grouped together as chronic obstructive pulmonary disease. This category includes both emphysema and chronic bronchitis. Chronic bronchitis refers to the condition of chronic or recurrent excess production of mucus (phlegm, sputum) in the bronchial tree. Normally, mucus acts to protect the lung from infection and injury. When mucus is overproduced as it is in chronic bronchitis, patients often develop complications. The most important complications that patients with chronic bronchitis develop include pneumonia and airflow obstruction (difficulty moving air through the respiratory passages of the lung). Either of these complications can lead to significant disability or even death.
The long-term objective of these studies is to increase our understanding of the role that lung mucins play in tobacco-related chronic bronchitis. Mucins make up a large part of mucus. Recently, molecular cloning experiments have shown that mucins are actually a family of at least nine different types of proteins. Some of these mucins are normally made by the lung. Our studies are designed to determine whether the number of cells producing mucins change with tobacco smoking or whether the types of mucins produced by the lung cells are different from the mucins produced by people who do not smoke. Our experiments are also designed to determine which types of mucins are produced when patients develop chronic bronchitis and chronic bronchitis complicated by airflow obstruction. Finally, some of the studies proposed in this application are designed to investigate the role of inflammation within the bronchial tree and whether or not the white blood cells and body substances that make up the inflammatory reaction influence the type and amount of mucins produced by smokers and patients with tobacco-related chronic bronchitis.
Human lung tissue obtained after surgical removal of lungs will provide us with experimental material for the studies. The scientific techniques that will be used to study mucins will include sophisticated microscopic methods that will allow us to accurately measure the amount of different mucin genes that are active in the lung cells. For some mucins, the relative amount that are actually produced will also be measured. Special markers that can be applied to tissues will help us identify, under a microscope, the cells and cell products that are involved in lung mucin production. Careful methods of lung tissue dissection will let us compare any differences of mucin production that occur at different places along the bronchial tree.
Overall, the information obtained from these studies will help us better understand the lung mucins and how they are affected by tobacco smoke. This information may provide us with ideas for better treatments for people who have developed chronic bronchitis from smoking. |
|Protease XXIV increases detection of mucin gene expression during in situ hybridization in archival tissue
|Periodical: Journal of Histochemistry and Cytochemistry
|Authors: Rheinhardt JR, Finkbeiner WE