Abstract

The long term goal is to understand the role of mucociliary clearance in the maintenance of bronchial hygiene and how this may be compromised by drugs, disease and inhaled pollutants. We hope to learn how to prevent diseases of the airways, alleviate the symptoms, arrest the pathology, and eventually reverse compromised physiological function. Inhaled pollutants both cause and aggravate diseases of the airways of the lungs. The retention of mucus in the airways due to pulmonary insult is a major factor leading to increased morbidity and mortality. The major mechanism responsible for the transport of mucus from the lungs is the beating of cilia. The neurogenic pathways, mediators and mechanisms whereby pollutants effect their response on ciliary beat frequency is not well understood. We postulate that pollutants stimulate C-fibers which initiate a neural reflex that is mediated via the vagus that has both cholinergic and peptidergic components. In addition, mediator release from mast cells may play an important role. Agents or mediators may exert their effect predominantly on the luminal or basolateral side of the epithelium. Two specific assays for ciliary beat frequency (CBF) using laser light scattering will be used in concert to test our hypotheses. One assay will measure CBF in the trachea of the intact dog and the other will measure CBF on tracheal tissue samples, derived from these same dogs, mounted in a two sided chamber in which either the luminal or basolateral side of the epithelium can be independently irrigated with the test agent(s). Capsaicin, a demonstrated stimulant of C-fibers, will be used as a surrogate pollutant. Having established the dose-response of CBF to capsaicin, that component not mediated via the vagus that is due to mediator release from mast cells will be determined by stabilizing the mast cells with cromolyn sodium. The vagal component will be investigated by a vagal cold block and the cholinergic component of the vagal reflex determined by administration of atropine. The response of the two putative peptidergic components of the vagal reflex, substance P (SP) and vasointestinal peptide (VIP), will then be evaluated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES004317-02
Application #
3252392
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1987-05-01
Project End
1990-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Illinois at Chicago
Department
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612

  Publications

Besseris, George J; Yeates, Donovan B (2007) Rotating magnetic particle microrheometry in biopolymer fluid dynamics: mucus microrheology. J Chem Phys 127:105106
Yeates, D B; Mussatto, D J; Hameister, W M et al. (2001) Bronchial, alveolar, and vascular-induced anaphylaxis and irritant-induced cardiovascular and pulmonary responses. Environ Health Perspect 109 Suppl 4:513-22
Winters, S L; Yeates, D B (1997) Roles of hydration, sodium, and chloride in regulation of canine mucociliary transport system. J Appl Physiol 83:1360-9
Yeates, D B; Daza, A V; Mussatto, D J (1997) Bronchial and alveolar allergen-induced anaphylaxis and the stimulation of bronchial mucociliary clearance in ragweed-sensitized dogs. Proc Assoc Am Physicians 109:440-52
Winters, S L; Yeates, D B (1997) Interaction between ion transporters and the mucociliary transport system in dog and baboon. J Appl Physiol 83:1348-59
Chandra, T; Yeates, D B; Miller, I F et al. (1994) Stationary and nonstationary correlation-frequency analysis of heterodyne mode laser light scattering: magnitude and periodicity of canine tracheal ciliary beat frequency in vivo. Biophys J 66:878-90
Eljamal, M; Wong, L B; Yeates, D B (1994) Capsaicin-activated bronchial- and alveolar-initiated pathways regulating tracheal ciliary beat frequency. J Appl Physiol 77:1239-45
Duff, B E; Wenig, B L; Applebaum, E L et al. (1994) Tracheal reconstruction using an epithelial equivalent. Laryngoscope 104:409-14
Hameister, W M; Wong, L B; Yeates, D B (1992) Tracheal ciliary beat frequency in baboons: effects of peripheral histamine and capsaicin. Agents Actions 35:200-7
Pillai, R S; Chandra, T; Miller, I F et al. (1992) Work of adhesion of respiratory tract mucus. J Appl Physiol 72:1604-10

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