To fulfill its role of protecting the deep, sensitive, gas exchanging alveolar regions, the mucociliary system responds via the interaction of both neural and humoral pathways activated by unnatural environments in either central or peripheral regions of the lungs. Irritant, toxic or pathogenic challenges may result in defensive responses designed to maintain pulmonary homeostasis, or they may result in responses that lead to impaired mucociliary function, with its consequent effects on gas exchange. The agents to be studied, capsaicin, sulfur dioxide, oxygen and Ascaris suum antigen, mediate their effects on the mucociliary transport system through a number of pathways and mechanisms, including sympathetic, parasympathetic, cyclooxygenase, and the release of intracellular mediators, depending both on the agent involved and the site of insult. The test agents were chosen to investigate both the diversity of pathways whereby mucociliary transport is regulated and the contrasting effects that each of these agents is predicted to have on mucociliary clearance. Using this approach, we will formulate a more comprehensive model of the pathways and physiological consequences of the mucociliary system's response to irritants. To accomplish this we will use the following in vivo canine assays developed in this laboratory: ciliary beat frequency (CBF), tracheal mucus velocity (TKV), bronchial mucociliary clearance (BMC) and lower airway glycoprotein output (IAGO). To evaluate the importance of these parameters in maintaining effective mucociliary transport, we will use data from these in vivo studies combined with rheological data derived by magnetic rheometry and from in vitro CBF studies of the effects of agents on the characteristics of the metachronal wave to develop models of the mucociliary transport system. It is by understanding these pathways and mechanisms that the significance of the role of the mucociliary transport system and its components in pulmonary homeostasis can be determined, abnormalities in its response can be defined, and scientific rationales for therapeutic interventions of impaired function can be developed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
3R01ES004317-08S1
Application #
2153641
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1987-05-01
Project End
1996-08-31
Budget Start
1994-09-01
Budget End
1996-08-31
Support Year
8
Fiscal Year
1996
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
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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