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Measurement of Fluid Secretion from Intact Airway Submucosal Glands

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Cystic Fibrosis

Abstract

Human airways are kept sterile by a mucosal innate defense system that includes mucus secretion. Mucus is secreted in healthy upper airways primarily by submucosal glands and consists of defense molecules mixed with mucins, electrolytes, and water and is also a major component of sputum. Mucus traps pathogens and mechanically removes them via mucociliary clearance while inhibiting their growth via molecular (e.g., lysozyme) and cellular (e.g., neutrophils, macrophages) defenses. Fluid secretion rates of single glands in response to various mediators can be measured by trapping the primary gland mucus secretions in an oil layer, where they form spherical bubbles that can be optically measured at any desired interval to provide detailed temporal analysis of secretion rates. The composition and properties of the mucus (e.g., solids, viscosity, pH) can also be determined. These methods have now been applied to mice, ferrets, cats, pigs, sheep, and humans, with a main goal of comparing gland secretion in control and CFTR-deficient humans and animals.

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Acknowledgments

We are grateful to the transplant patients and their families whose cooperation provided the tissues needed for studies of human gland secretion. For help in obtaining informed consent from patients we thank D. Weill, N.R. Henig, J. Theodore, T.E. Robinson, M. Wine, and K. Tran. For access to surgical tissues we thank B.A. Reitz, G.J. Berry, R.C. Robbins, R.I. Whyte, and the staff of the Stanford Transplant team. Jennifer Lyons provided useful discussions and comments. Technical help and data analysis were provided by Tracy Hsu, Christina Tseng, Molly Pam, Wei Chen, Sidney Chang, Kim Tran, and Jonathan Chen. The work was supported by NIH Grant DK-51817, the Cystic Fibrosis Foundation, and CFRI.

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Wine, J.J. et al. (2011). Measurement of Fluid Secretion from Intact Airway Submucosal Glands. In: Amaral, M., Kunzelmann, K. (eds) Cystic Fibrosis. Methods in Molecular Biology, vol 742. Humana Press. https://doi.org/10.1007/978-1-61779-120-8_6

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