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Environmental tobacco smoke effects on lung surfactant

Institution: University of California, Santa Barbara
Investigator(s): Joseph Zasadzinski, Ph.D.
Award Cycle: 1999 (Cycle 8) Grant #: 8RT-0077 Award: $423,216
Subject Area: Pulmonary Disease
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
The specific risks posed by environmental tobacco smoke (ETS) to non-smokers are not particularly well known at the physiological level, although quantifying these risks is an important public health and policy concern. A causal association between ETS exposure and lung cancer appears to exist; for example, nonsmokers married to smokers have a statistically significant higher risk of developing lung cancer than other nonsmokers. In addition to major diseases such as lung cancer, associations have been found between passive smoking at the workplace and chronic respiratory symptoms such as wheezing and cough; the severity of which depends on the extent of exposure. Respiratory effects of ETS are especially significant in infants and children exposed to parental smoking. Epidemiological studies have shown that children raised in homes with smokers have more coughing, wheezing, and respiratory illness compared to children raised in homes without smoking. However, these epidemiological studies cannot provide an explanation of how ETS affects various organs or processes in the body.

This proposal is designed to determine the effects of controlled exposure to environmental tobacco smoke on the chemical and morphological features of human lung surfactants. The surfactant lining of the alveoli, the small gas exchange sacs within the lung, plays an important part in proper lung function. Lung surfactant helps to minimize the energy required to breathe, helps to insure uniform lung inflation and deflation, and helps to clear the deep lung of chemical and particulate contaminants. Lung surfactant works by forming a thin layer that varies from one to no more than 10 molecular layers thick, at the interface between the liquid layer lining the alveolus and the air. This surfactant layer, just like the surfactants used to wash dishes or clean clothes, acts to lower the surface tension at this interface. As the alveolus expands and contracts, it works against the surface tension of this interface; without the surfactant layer to lower the tension, the lung could not inflate. Lung surfactant is unique in that it can almost eliminate surface tension entirely when you exhale, making breathing almost effortless. The unique mix of lipids and proteins in lung surfactant work together to create this film and the near zero surface tension.

Our previous work has shown that rather small changes in the lipid and protein composition of lung surfactant can lead to dramatic changes in surface tension. As ETS comes into contact with the surfactant layer, it is important to determine what ETS can do to the chemistry and morphology of the surfactant. We plan to measure surface tension and determine the morphology of lung surfactant monolayers on model liquids designed to mimic the fluid lining of the alveolus. We will expose these model liquids to various concentrations of side-stream smoke using a system developed at the Institute of Toxicology and Environmental Health at UC Davis. Lung surfactant monolayers will be spread over this smoke-conditioned liquid and the surface tension, viscosity, phase behavior, and morphology of the monolayer will be compared to control monolayers. Detailed chemical analysis of the lipids and proteins in lung surfactant will be conducted to help isolate the species in surfactant most susceptible to damage by ETS. We hope to be able to provide direct evidence of the effects of ETS on the lung surfactant system, and how these changes can lead to changes in respiratory health.
Publications

Conformational mapping of the N-terminal segment of surfactant protein B in lipid using 13 C - enhanced infrared spectroscopy
Periodical: Journal of Peptide Research Index Medicus:
Authors: Gordon LM, Lee KYC, Zasadzinski JA, Sherman MA, Waring AJ ABS
Yr: 2000 Vol: 55 Nbr: Abs: Pg: 330-347

The role of lung surfactant proteins and lipids in monolayer stability
Periodical: Biophysical Journal Index Medicus:
Authors: Ding J, Takamoto DY, von Nahmen A, et al ART
Yr: 0 Vol: Nbr: Abs: Pg:

Surfactant protein B and C analogs
Periodical: Molecular Genetics and Metabolism Index Medicus:
Authors: Waring AJ, Walther F, Zasadzinski J, Sherwood M ART
Yr: 2000 Vol: 71 Nbr: Abs: Pg: 342-351

Effects of lung surfactant proteins SP-B and SP-C and palmitic acid on monolayer stability
Periodical: Biophysical Journal Index Medicus:
Authors: Ding J, von Nahmen A, Takamoto DK, et al ART
Yr: 2001 Vol: 80 Nbr: Abs: Pg: 2262 - 2272

Interaction of lung surfactant proteins with anionic phospholipids
Periodical: Biophysical Journal Index Medicus:
Authors: Takamoto DY, Lipp MM, von Nahmen A, Lee KYC, Waring AJ, Zasadzinski J ART
Yr: 2001 Vol: 80 Nbr: Abs: Pg:

The incorporation of lung sufactant protein SP-B into lipid monolayers at the air-fluid interface
Periodical: Biophysical Journal Index Medicus:
Authors: Lee KYC, Majewski J, Kuhl TL, et al ART
Yr: 2001 Vol: 81 Nbr: Abs: Pg: 572 - 585

Changes in model lung surfactant monolayers induced by palmitic acid
Periodical: Langmuir Index Medicus:
Authors: Bringezu F, Ding J, Brezesinski G, Zasadzinski J ART
Yr: 2001 Vol: 17 Nbr: Abs: Pg: 4641 - 4648

A concentration dependent mechanism by which serum albumin inactivates replacement lung surfactants.
Periodical: Biophysical Journal Index Medicus:
Authors: Warriner HE, Ding J, Waring A, and Zasadzinski A ART
Yr: 2002 Vol: 82 Nbr: Abs: Pg: 835 - 842

Influence of pulmonary surfactant protein B on structures of condensed model lung surfactant monolayers.
Periodical: Langmuir Index Medicus:
Authors: Bringezu F, Ding J, Brezesinski G, Waring A and Zasadzinski A ART
Yr: 2002 Vol: 18 Nbr: Abs: Pg: 2319 - 2325

Influence of palmitic acid and hexidecanol on the phase transition temperatures and molecular packing of DPPC monolayers at the air-water interface.
Periodical: Journal of Chemical Physics Index Medicus:
Authors: Lee KYC et al. ART
Yr: 2002 Vol: 115 Nbr: Abs: Pg: 774 - 783

Viscosity of two-dimensional suspensions.
Periodical: Physical Review Letters Index Medicus:
Authors: Ding J, Warriner HE, and Zasadzinski JA ART
Yr: 2002 Vol: 88 Nbr: 168102 Abs: Pg: 1 - 4

A magnetic needle viscometer for langmuir monolayers.
Periodical: Langmuir Index Medicus:
Authors: Ding J, Warriner HE, Schwartz DK, and Zasadzinski J ART
Yr: 2002 Vol: 18 Nbr: Abs: Pg: 2800 - 2806

Interaction of lung surfactant proteins with anionic phospholipids.
Periodical: Biophysical Journal Index Medicus:
Authors: Takamoto DY, et al. ART
Yr: 2001 Vol: 81 Nbr: Abs: Pg: 153 - 169

Stable ordering in langmuir-blodgett films.
Periodical: Science Index Medicus:
Authors: Takamoto DY, et al. ART
Yr: 2001 Vol: 293 Nbr: Abs: Pg: 1292 - 1295

Conformational mapping of the N-terminal segment of surfactant protein B in lipid using 13C-enhanced fourier transform infrared spectroscopy.
Periodical: Journal of Peptide Research Index Medicus:
Authors: Gordon LM, et al. ART
Yr: 2000 Vol: 55 Nbr: Abs: Pg: 330 - 347

The physics and physiology of lung surfactants.
Periodical: Current Opinion in Colloid and Interface Science Index Medicus:
Authors: Zasadzinski JA, Ding J, Warriner H, and Bringezu F ART
Yr: 2001 Vol: 6 Nbr: Abs: Pg: 506 - 513

The incorporation of lung surfactant specific protein SP-B into lipid monolayers at the air-fluid interface.
Periodical: Material Research Society Symposium Proceedings: Applications of Synchrotron Radiation Techniques to Materials Science. Index Medicus:
Authors: Lee KYC, Majewski J, Kuhl TL, et al. ART
Yr: 2000 Vol: 590 Nbr: Abs: Pg: 177 - 182

Environmental tobacco smoke effects on the primary lipids of lung surfactants.
Periodical: Langmuir Index Medicus:
Authors: Bringezu F, Ding J, and Zasadzinski J ART
Yr: 2003 Vol: 19 Nbr: Abs: Pg: 2900-2907