CFTR
Link Between Clinical Pathology and Molecular
Defect
It remains unclear exactly how the altered
production of CFTR
results in the pathology observed in CF. There are a number of theories. At
present the extent to which each of these contributes, if at all, to the
observed pathology has not been established.
The low volume hypothesis proposes that due to the impaired chloride secretion and the high sodium absorption, water is absorbed and the airway surface liquid becomes depleted. This renders the cilia unable to beat effectively and the mucociliary clearance of secretions and bacteria is impaired leading to the increased susceptibility to infection seen in CF subjects.
The high salt hypothesis suggests that the impaired chloride transport results in abnormally high salt concentrations in the airway surface liquid, which reduces the effectiveness of natural antibiotics such as defensins, lysozyme and lactoferrin and consequentially resistance to bacterial infection.
There is also evidence to suggest that mutations in CFTR result in an increased number of pathogen receptors on respiratory cells. This leads to the increased binding of bacterial pathogens, including P. aeruginosa that is observed in CF airways.
It is believed that CFTR may be involved in the ingestion of the bacterium P. aeruginosa into epithelial cells and its clearance from the lungs. The mechanism is poorly understood at present. However in the absence of CFTR it is thought that this process is unable to occur efficiently resulting in the increased numbers of bacteria in the lungs characteristic of CF.
For quick & easy reference to definitions of scientific and medical terms visit one of the on-line dictionaries