Mucociliary clearance of inhaled particles from the tracheobronchial tree is an important defense mechanism of the lung. A failure of this clearance mechanism results in retained mucous secretions and a predisposition to pulmonary infection. Circumstantial evidence indicates that a balance in the rate of secretions of ions, water and mucous glycoproteins by the airway epithelium help regulate mucociliary clearance. It is thought that a major portion of the total airway secretions are produced by the submucosal glands of the airway epithelium. Thus, alterations in the mechanisms controlling glandular secretions may be involved in the failure of mucociliary clearance in certain pulmonary diseases. Prior studies of the control of secretion by the airway epithelium have generally employed intact tracheal tissue, in vitro. The use of intact tissue has hindered the ability of investigators to adequately separate the physiological responses of gland cells from those of the surface epithelium. I have developed a technique to isolate viable submucosal gland cells from cat trachea. In the proposed studies, the presence of cholinergic and adrenergic receptors in glandular cell homogenates will be determined using radiolabelled ligands. Receptors to be characterized, if present, include muscarinic cholinergic, Alpha-adrenergic and Beta-adrenergic receptors. I will also study mucous glycoprotein secretion by isolated gland cells. Changes in mucous glycoprotein secretion rates in response to tracheal secretagogues will be determined. Secreted mucous glycoproteins will be characterized biochemically. I also plan to determine if the cyclic nucleotides (cyclic AMP and cyclic GMP) are involved in secretagogue-induced secretion by these cells. Once normal secretory function is defined, the effects of viral infection (influenza type A and respiratory syncytial virus) on the rate and control of mucous glycoprotein secretion will be studied.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032949-03
Application #
3344524
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1984-09-01
Project End
1987-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Medicine
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Culp, D J; Latchney, L R; Frampton, M W et al. (1995) Composition of human airway mucins and effects after inhalation of acid aerosol. Am J Physiol 269:L358-70
Culp, D J; Latchney, L R (1993) Mucinlike glycoproteins from cat tracheal gland cells in primary culture. Am J Physiol 265:L260-9
Culp, D J; Lee, D K; Penney, D P et al. (1992) Cat tracheal gland cells in primary culture. Am J Physiol 263:L264-75
Culp, D J; Graham, L A; Latchney, L R et al. (1991) Rat sublingual gland as a model to study glandular mucous cell secretion. Am J Physiol 260:C1233-44
Culp, D J; McBride, R K; Graham, L A et al. (1990) Alpha-adrenergic regulation of secretion by tracheal glands. Am J Physiol 259:L198-205
Jay, G D; Culp, D J; Jahnke, M R (1990) Silver staining of extensively glycosylated proteins on sodium dodecyl sulfate-polyacrylamide gels: enhancement by carbohydrate-binding dyes. Anal Biochem 185:324-30
Moreira, J E; Tabak, L A; Bedi, G S et al. (1989) Light and electron microscopic immunolocalization of rat submandibular gland mucin glycoprotein and glutamine/glutamic acid-rich proteins. J Histochem Cytochem 37:515-28
Gentry, S E; Culp, D J; Roberts Jr, N J et al. (1988) Influenza virus infection of tracheal gland cells in culture. J Virol 62:1524-9
Marin, M G; Culp, D J (1986) Isolation and culture of submucosal gland cells. Clin Chest Med 7:239-45
Culp, D J; Marin, M G (1986) Characterization of muscarinic cholinergic receptors in cat tracheal gland cells. J Appl Physiol 61:1375-82