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Lack of applicability of the enterocyte chloride ion secretion paradigm to the pathology of cystic fibrosis

Lucas, M. L. (2017) Lack of applicability of the enterocyte chloride ion secretion paradigm to the pathology of cystic fibrosis. Archives of Asthma, Allergy and Immunology, 1, 061-085.

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Abstract

This review examines of the concept of a defective chloride channel in epithelial cells being a major cause of cystic fi brotic pathophysiology. The central concept of the defective chloride ion channel paradigm is that faulty CFTR protein or failed delivery of CFTR protein to the mucosal membrane of epithelial cells is the basis of cystic fi brosis. Defective placement or function of CFTR prevents hydration of bronchial mucus that is normally caused by epithelial cells; these are capable through chloride ion secretion of transporting fl uid to the mucosal surface. This concept relies heavily on a paradigm taken from intestinal physiology-namely that the intestinal epithelial cell secretes chloride ion and fl uid and that this has conferred heterozygote selective advantage in carriers of the cystic fibrosis gene. This present review examines the evidence for that hypothesis and assembles evidence from past studies that it is the smooth muscle cell that is of greater relevance. This review does not aim to provide an overview of current research into cystic fi brosis. The intention is to provide an overview of past research that led to the concept of a failure of epithelial cells to hydrate bronchial mucus because of compromised CFTR function. It is important to present all past evidence for aspects of the chloride secretion hypothesis and its associated heterozygote advantage concept so that the important evidential milestones can be re-assessed.

Item Type:	Articles
Additional Information:	A critique of the epithelial cell chloride secretion view together with advocacy of smooth muscle pathology as the underlying pathology of cystic fibrosis.
Keywords:	Cystic fibrosis, smooth muscle.
Status:	Published
Refereed:	Yes
Glasgow Author(s) Enlighten ID:	Lucas, Dr Michael
Authors:	Lucas, M. L.
College/School:	College of Medical Veterinary and Life Sciences > School of Life Sciences
Research Group:	M L Lucas
Journal Name:	Archives of Asthma, Allergy and Immunology
Journal Abbr.:	AAIA
Publisher:	Heighten Publications
Copyright Holders:	Copyright © 2017 Lucas ML
First Published:	First published in Archives of Asthma, Allergy and Immunology 1: 061-085
Publisher Policy:	Reproduced under a Creative Commons License

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Deposit and Record Details

ID Code:	158081
Depositing User:	Dr Michael Lucas
Datestamp:	01 Mar 2018 09:22
Last Modified:	28 May 2020 18:24
Date of acceptance:	20 October 2017
Date of first online publication:	23 October 2017
Date Deposited:	1 March 2018
Data Availability Statement:	No